Targeted Radionuclide Therapy of Painful Bone Metastases: Past Developments, Current Status, Recent Advances and Future Directions

doi:10.2174/0929867326666190201142814
摘要

由继发性骨骼恶性肿瘤引起的骨痛是癌症患者最常见的慢性疼痛类型之一，可导致生活质量的迅速恶化。使用寻骨放射性药物的放射性核素治疗是一种有效的缓解症状性骨转移的治疗方式，其基础是在骨转移部位定位放射药剂，以提供局灶性细胞毒性水平的辐射。寻骨放射性药物不仅提供姑息效益，而且在整体和无进展生存率方面提高临床结果。用于或可能以离子形式或与载体分子结合用于治疗骨转移的治疗放射性核素的清单正在稳步扩大。这篇文章提供了一个基于目前批准的研究和潜在有用的放射性核素的骨靶向放射性药物的医疗设备的叙述回顾，并研究了它们在治疗疼痛性骨转移的疗效。此外，文章还强调了过程，机遇，和挑战涉及发展骨头寻求放射性药物。在该类药物中，Radium-223是第一种表现出对有骨转移的抗去势前列腺癌(CRPC)患者总体生存优势的药物。本文综述了放射药物治疗骨痛的最新进展、临床应用现状，并展望了该领域的发展前景。
关键词: 骨，癌症，疼痛，姑息疗法，放射性核素，放射性药物，转移，二磷酸盐，羟基磷灰石。
« Previous Next »
[1] 
Bauman, G.; Charette, M.; Reid, R.; Sathya, J. Radiopharmaceuticals for the palliation of painful bone metastasis-a systemic review. Radiother. Oncol.,  2005, 75(3), 258-270.
[http://dx.doi.org/10.1016/j.radonc.2005.03.003] [PMID: 16299924] 
[2] 
Callstrom, M.R.; Charboneau, J.W. Image-guided palliation of painful metastases using percutaneous ablation. Tech. Vasc. Interv. Radiol.,  2007, 10(2), 120-131.
[http://dx.doi.org/10.1053/j.tvir.2007.09.003] [PMID: 18070690] 
[3] 
Chiacchio, S.; Mazzarri, S.; Lorenzoni, A.; Nyakale, N.; Boni, G.; Borsò, E.; Alsharif, A.; Grosso, M.; Manca, G.; Greco, C.; Volterrani, D.; Mariani, G. Radionuclide therapy and integrated protocols for bone metastases. Q. J. Nucl. Med. Mol. Imaging,  2011, 55(4), 431-447.
[PMID: 21738116] 
[4] 
Christensen, M.H.; Petersen, L.J. Radionuclide treatment of painful bone metastases in patients with breast cancer: a systematic review. Cancer Treat. Rev.,  2012, 38(2), 164-171.
[http://dx.doi.org/10.1016/j.ctrv.2011.05.008] [PMID: 21683530] 
[5] 
Jansen, D.R.; Krijger, G.C.; Kolar, Z.I.; Zonnenberg, B.A.; Zeevaart, J.R. Targeted radiotherapy of bone malignancies. Curr. Drug Discov. Technol.,  2010, 7(4), 233-246.
[http://dx.doi.org/10.2174/157016310793360675] [PMID: 21034411] 
[6] 
Chow, E. Update on radiation treatment for cancer pain. Curr. Opin. Support. Palliat. Care,  2007, 1(1), 11-15.
[http://dx.doi.org/10.1097/SPC.0b013e328133f5d8] [PMID: 18660718] 
[7] 
Hillegonds, D.J.; Franklin, S.; Shelton, D.K.; Vijayakumar, S.; Vijayakumar, V. The management of painful bone metastases with an emphasis on radionuclide therapy. J. Natl. Med. Assoc.,  2007, 99(7), 785-794.
[PMID: 17668645] 
[8] 
Falkmer, U.; Järhult, J.; Wersäll, P.; Cavallin-Ståhl, E. A systematic overview of radiation therapy effects in skeletal metastases. Acta Oncol.,  2003, 42(5-6), 620-633.
[http://dx.doi.org/10.1080/02841860310014895] [PMID: 14596519] 
[9] 
Ben-Josef, E.; Porter, A.T. Radioisotopes in the treatment of bone metastases. Ann. Med.,  1997, 29(1), 31-35.
[http://dx.doi.org/10.3109/07853899708998741] [PMID: 9073322] 
[10] 
Serafini, A.N. Current status of systemic intravenous radiopharmaceuticals for the treatment of painful metastatic bone disease. Int. J. Radiat. Oncol. Biol. Phys.,  1994, 30(5), 1187-1194.
[http://dx.doi.org/10.1016/0360-3016(94)90327-1] [PMID: 7525518] 
[11] 
Macedo, F.; Ladeira, K.; Pinho, F.; Saraiva, N.; Bonito, N.; Pinto, L.; Goncalves, F. Bone metastases: an overview. Oncol. Rev.,  2017, 11(1), 321.
[http://dx.doi.org/10.4081/oncol.2017.321] [PMID: 28584570] 
[12] 
Harrison, M.R.; Wong, T.Z.; Armstrong, A.J.; George, D.J. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease. Cancer Manag. Res.,  2013, 5, 1-14.
[http://dx.doi.org/10.2147/CMAR.S25537] [PMID: 23326203] 
[13] 
Lewington, V.J.; Lewington, V.J. Targeted radionuclide therapy for bone metastases. Eur. J. Nucl. Med.,  1993, 20(1), 66-74.
[http://dx.doi.org/10.1007/BF02261248] [PMID: 7678397] 
[14] 
Raggatt, L.J.; Partridge, N.C. Cellular and molecular mechanisms of bone remodeling. J. Biol. Chem.,  2010, 285(33), 25103-25108.
[http://dx.doi.org/10.1074/jbc.R109.041087] [PMID: 20501658] 
[15] 
Bilezikian, J.P.; Raisz, L.G.; Rodan, G.A. Principles of Bone Biology, 2nd ed; , 2002. 
[16] 
Schneider, A.; Kalikin, L.M.; Mattos, A.C.; Keller, E.T.; Allen, M.J.; Pienta, K.J.; McCauley, L.K. Bone turnover mediates preferential localization of prostate cancer in the skeleton. Endocrinology,  2005, 146(4), 1727-1736.
[http://dx.doi.org/10.1210/en.2004-1211] [PMID: 15637291] 
[17] 
Santini, D.; Galluzzo, S.; Zoccoli, A.; Pantano, F.; Fratto, M.E.; Vincenzi, B.; Lombardi, L.; Gucciardino, C.; Silvestris, N.; Riva, E.; Rizzo, S.; Russo, A.; Maiello, E.; Colucci, G.; Tonini, G. New molecular targets in bone metastases. Cancer Treat. Rev.,  2010, 36(Suppl. 3), S6-S10.
[http://dx.doi.org/10.1016/S0305-7372(10)70013-X] [PMID: 21129612] 
[18] 
Jung, Y.; Wang, J.; Schneider, A.; Sun, Y.X.; Koh-Paige, A.J.; Osman, N.I.; McCauley, L.K.; Taichman, R.S. Regulation of SDF-1 (CXCL12) production by osteoblasts; a possible mechanism for stem cell homing. Bone,  2006, 38(4), 497-508.
[http://dx.doi.org/10.1016/j.bone.2005.10.003] [PMID: 16337237] 
[19] 
Koutsilieris, M. Osteoblastic metastasis in advanced prostate cancer. Anticancer Res.,  1993, 13(2), 443-449.
[PMID: 8517661] 
[20] 
Koutsilieris, M. Skeletal metastases in advanced prostate cancer: cell biology and therapy. Crit. Rev. Oncol. Hematol.,  1995, 18(1), 51-64.
[http://dx.doi.org/10.1016/1040-8428(94)00122-A] [PMID: 7535057] 
[21] 
Bagi, C.M. Targeting of therapeutic agents to bone to treat metastatic cancer. Adv. Drug Deliv. Rev.,  2005, 57(7), 995-1010.
[http://dx.doi.org/10.1016/j.addr.2004.12.014] [PMID: 15876400] 
[22] 
Hayward, J.L.; Carbone, P.P.; Heuson, J.C.; Kumaoka, S.; Segaloff, A.; Rubens, R.D. Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer,  1977, 39(3), 1289-1294.http://dx.doi.org/10.1002/1097-0142(197703)39:3< 1289: :AID CNCR2820390340>3.0.CO;2-F PMID: 912660
[23] 
Ferlay, J.; Shin, H.R.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer,  2010, 127(12), 2893-2917.
[http://dx.doi.org/10.1002/ijc.25516] [PMID: 21351269] 
[24] 
Silberstein, E.B.; Williams, C. Strontium-89 therapy for the pain of osseous metastases. J. Nucl. Med.,  1985, 26(4), 345-348.
[PMID: 3920361] 
[25] 
Coleman, R.E. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat. Rev.,  2001, 27(3), 165-176.
[http://dx.doi.org/10.1053/ctrv.2000.0210] [PMID: 11417967] 
[26] 
Roodman, G.D. Mechanisms of bone lesions in multiple myeloma and lymphoma. Cancer,  1997, 80(8)(Suppl.), 1557-1563.
[http://dx.doi.org/10.1002/(SICI)1097-0142(19971015)80:8+<1557:AID-CNCR5>3.0.CO;2-H] [PMID: 9362422] 
[27] 
Emami, B.; Lyman, J.; Brown, A.; Coia, L.; Goitein, M.; Munzenrider, J.E.; Shank, B.; Solin, L.J.; Wesson, M. Tolerance of normal tissue to therapeutic irradiation. Int. J. Radiat. Oncol. Biol. Phys.,  1991, 21(1), 109-122.
[http://dx.doi.org/10.1016/0360-3016(91)90171-Y] [PMID: 2032882] 
[28] 
Salazar, O.M.; Scarantino, C.W.; Rubin, P.; Feldstein, M.L.; Keller, B.E. Total (half-body) systemic irradiation for occult metastases in non-small cell lung cancer: an Eastern cooperative oncology group pilot report. Cancer,  1980, 46(9), 1932-1944.http://dx.doi.org/10.1002/1097-0142(19801101)46:9<1932:: AID-CNCR2820460907>3.0.CO;2-9 PMID: 7427899
[29] 
Pal, S.; Dutta, S.; Adhikary, S.S.; Bhattacharya, B.; Ghosh, B.; Patra, N.B. Hemi body irradiation: An economical way of palliation of pain in bone metastasis in advanced cancer. South Asian J. Cancer,  2014, 3(1), 28-32.
[http://dx.doi.org/10.4103/2278-330X.126513] [PMID: 24665443] 
[30] 
Gocheva, L.; Todorov, J.; Danon, S. Tolerance of half-body irradiation as systemic therapy for patients with locally advanced breast cancer. Med. Pediatr. Oncol.,  1999, 33(6), 558-562.http://dx.doi.org/10.1002/(SICI)1096-911X(199912)33:6 <558::AID-MPO6>3.0.CO;2-I
[PMID: 10573579] 
[31] 
Smith, H.; Navani, A.; Fishman, S.M. Radiopharmaceuticals for palliation of painful osseous metastases. Am. J. Hosp. Palliat. Care,  2004, 21(4), 303-313.
[http://dx.doi.org/10.1177/104990910402100415] [PMID: 15315195] 
[32] 
Msaouel, P.; Pissimissis, N.; Halapas, A.; Koutsilieris, M. Mechanisms of bone metastasis in prostate cancer: clinical implications. Best Pract. Res. Clin. Endocrinol. Metab.,  2008, 22(2), 341-355.
[http://dx.doi.org/10.1016/j.beem.2008.01.011] [PMID: 18471791] 
[33] 
Powles, T.; Paterson, S.; Kanis, J.A.; McCloskey, E.; Ashley, S.; Tidy, A.; Rosenqvist, K.; Smith, I.; Ottestad, L.; Legault, S.; Pajunen, M.; Nevantaus, A.; Männistö, E.; Suovuori, A.; Atula, S.; Nevalainen, J.; Pylkkänen, L. Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer. J. Clin. Oncol.,  2002, 20(15), 3219-3224.
[http://dx.doi.org/10.1200/JCO.2002.11.080] [PMID: 12149294] 
[34] 
Pecher, C. Biological investigations with radioactive calcium and strontium. Proc. Soc. Exp. Biol. Med.,  1941, 46, 86-91.
[http://dx.doi.org/10.3181/00379727-46-11899] 
[35] 
Pecher, C. Biological investigations with radioactive calcium and strontium: preliminary report on the use of radioactive strontium in treatment of metastatic bone cancer. Univ. Calif. Publ. Pharmacol.,  1942, 2, 1117-1149.
[36] 
Potsaid, M.; Irwin, R.; Castronova, F. Phosphorous 32 EHDP clinical study of patients with prostate carcinoma and bone metastases. J. Nucl. Med.,  1976, 17, 548-549.
[37] 
Silberstein, E.B. The treatment of painful osseous metastases with phosphorus-32-labeled phosphates. Semin. Oncol.,  1993, 20(3)(Suppl. 2), 10-21.
[PMID: 7684860] 
[38] 
Berlin, N.I. Treatment of the myeloproliferative disorders with 32P. Eur. J. Haematol.,  2000, 65(1), 1-7.
[http://dx.doi.org/10.1034/j.1600-0609.2000.9r119.x] [PMID: 10914933] 
[39] 
Balink, H.; Sijmons, E.A.; Zonnenberg, B.A.; De Klerk, J.M. Repetitive phosphorus-32 peritoneal instillations in a patient with malignant ascites. Clin. Nucl. Med.,  2003, 28(7), 545-547.
[http://dx.doi.org/10.1097/00003072-200307000-00002] [PMID: 12819405] 
[40] 
Zacho, H.D.; Karthigaseu, N.N.; Fonager, R.F.; Petersen, L.J. Treatment with bone-seeking radionuclides for painful bone metastases in patients with lung cancer: a systematic review. BMJ Support. Palliat. Care,  2017, 7(3), 230-237.
[http://dx.doi.org/10.1136/bmjspcare-2015-000957] [PMID: 26817791] 
[41] 
Guerra Liberal, F.D.C.; Tavares, A.A.S.; Tavares, J.M.R.S. Palliative treatment of metastatic bone pain with radiopharmaceuticals: A perspective beyond Strontium-89 and Samarium-153. Appl. Radiat. Isot.,  2016, 110, 87-99.
[http://dx.doi.org/10.1016/j.apradiso.2016.01.003] [PMID: 26773820] 
[42] 
Tong, D.; Gillick, L.; Hendrickson, F.R. The palliation of symptomatic osseous metastases: final results of the study by the radiation therapy oncology group. Cancer,  1982, 50(5), 893-899.http://dx.doi.org/10.1002/1097-0142(19820901)50:5<893:: AID-CNCR2820500515>3.0.CO;2-Y
[PMID: 6178497] 
[43] 
Damerla, V.; Packianathan, S.; Boerner, P.S.; Jani, A.B.; Vijayakumar, S.; Vijayakumar, V. Recent developments in nuclear medicine in the management of bone metastases: a review and perspective. Am. J. Clin. Oncol.,  2005, 28(5), 513-520.
[http://dx.doi.org/10.1097/01.coc.0000162425.55457.10] [PMID: 16199993] 
[44] 
Johnstone, C.; Lutz, S.T. External beam radiotherapy and bone metastases. Ann. Palliat. Med.,  2014, 3(2), 114-122.
[http://dx.doi.org/10.3978/j.issn.2224-5820.2014.04.06] [PMID: 25841509] 
[45] 
Choi, J.Y. Treatment of bone metastasis with bone-targeting radiopharmaceuticals. Nucl. Med. Mol. Imaging,  2018, 52(3), 200-207.
[http://dx.doi.org/10.1007/s13139-017-0509-2] [PMID: 29942398] 
[46] 
Schmidt, C.G.; Firusian, N. 89-Sr for the treatment of incurable pain in patient with neoplastic osseous infiltrations. Int. J. Clin. Pharmacol.,  1974, 7(3), 199-205.
[PMID: 4855457] 
[47] 
Firusian, N.; Mellin, P.; Schmidt, C.G. Results of 89strontium therapy in patients with carcinoma of the prostate and incurable pain from bone metastases: a preliminary report. J. Urol.,  1976, 116(6), 764-768.
[http://dx.doi.org/10.1016/S0022-5347(17)59002-3] [PMID: 1003647] 
[48] 
Firusian, N. Endoossale isotopen-therapie maligner skeleter krankungen. Z. Krebsforsch.,  1978, 91, 143-156.
[http://dx.doi.org/10.1007/BF00284021] 
[49] 
McEwan, A.J. Unsealed source therapy of painful bone metastases: an update. Semin. Nucl. Med.,  1997, 27(2), 165-182.
[http://dx.doi.org/10.1016/S0001-2998(97)80046-3] [PMID: 9144858] 
[50] 
Paes, F.M.; Ernani, V.; Hosein, P.; Serafini, A.N. Radiopharmaceuticals: when and how to use them to treat metastatic bone pain. J. Support. Oncol.,  2011, 9(6), 197-205.
[http://dx.doi.org/10.1016/j.suponc.2011.06.004] [PMID: 22055888] 
[51] 
Poste, G.; Fidler, I.J. The pathogenesis of cancer metastasis. Nature,  1980, 283(5743), 139-146.
[http://dx.doi.org/10.1038/283139a0] [PMID: 6985715] 
[52] 
Fidler, I.J. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat. Rev. Cancer,  2003, 3(6), 453-458.
[http://dx.doi.org/10.1038/nrc1098] [PMID: 12778135] 
[53] 
Smith, H.S. Painful boney metastases. Ann. Palliat. Med.,  2012, 1(1), 14-31.
[http://dx.doi.org/10.3978/j.issn.2224-5820.2012.02.03] [PMID: 25841427] 
[54] 
Christo, P.J.; Mazloomdoost, D. Cancer pain and analgesia. Ann. N. Y. Acad. Sci.,  2008, 1138, 278-298.
[http://dx.doi.org/10.1196/annals.1414.033] [PMID: 18837907] 
[55] 
Jadad, A.R.; Browman, G.P. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA,  1995, 274(23), 1870-1873.
[http://dx.doi.org/10.1001/jama.1995.03530230056031] [PMID: 7500538] 
[56] 
Thomas, J.R.; Cooney, G.A.; Slatkin, N.E. Palliative care and pain: new strategies for managing opioid bowel dysfunction. J. Palliat. Med.,  2008, 11(Suppl. 1), S1-S19.
[http://dx.doi.org/10.1089/jpm.2008.9839.supp] [PMID: 18800914] 
[57] 
Eisenberg, E.; McNicol, E.; Carr, D.B. Opioids for neuropathic pain. Cochrane Database Syst. Rev.,  2006, 19(3) CD006146
[http://dx.doi.org/10.1002/14651858.CD006146] [PMID: 16856116] 
[58] 
Loblaw, D.A.; Virgo, K.S.; Nam, R.; Somerfield, M.R.; Ben-Josef, E.; Mendelson, D.S.; Middleton, R.; Sharp, S.A.; Smith, T.J.; Talcott, J.; Taplin, M.; Vogelzang, N.J.; Wade, J.L., III; Bennett, C.L.; Scher, H.I. American Society of Clinical Oncology. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J. Clin. Oncol.,  2007, 25(12), 1596-1605.
[http://dx.doi.org/10.1200/JCO.2006.10.1949] [PMID: 17404365] 
[59] 
Selman, L.; Harding, R.; Gysels, M.; Speck, P.; Higginson, I.J. The measurement of spirituality in palliative care and the content of tools validated cross-culturally: a systematic review. J. Pain Symptom Manage.,  2011, 41(4), 728-753.
[http://dx.doi.org/10.1016/j.jpainsymman.2010.06.023] [PMID: 21306866] 
[60] 
Marsoni, S.; Hurson, S.; Eisenberger, M. Chemotherapy of bone metastases. Bone resorption, metastasis and diphosphonates.,  1985, 181-195.
[61] 
Tannock, I.F. Is there evidence that chemotherapy is of benefit to patients with carcinoma of the prostate? J. Clin. Oncol.,  1985, 3(7), 1013-1021.
[http://dx.doi.org/10.1200/JCO.1985.3.7.1013] [PMID: 3894584] 
[62] 
Lipton, A. Bisphosphonates and breast carcinoma. Cancer,  1997, 80(8)(Suppl.), 1668-1673.
[http://dx.doi.org/10.1002/(SICI)1097-0142(19971015)80:8+<1668:AID-CNCR17>3.0.CO;2-Y] [PMID: 9362434] 
[63] 
Gennari, G.; Francini, G.; Chierichetti, S.M.; Nami, R.; Gonelli, S.; Poilini, M. Salmon calcitonin treatment in bone metastases. Curr. Ther. Res. Clin. Exp.,  1989, 45, 804-812.
[64] 
Adami, S.; Salvagno, G.; Guarrera, G.; Bianchi, G.; Dorizzi, R.; Rosini, S.; Mobilio, G.; Lo Cascio, V. Dichloromethylene-diphosphonate in patients with prostatic carcinoma metastatic to the skeleton. J. Urol.,  1985, 134(6), 1152-1154.
[http://dx.doi.org/10.1016/S0022-5347(17)47663-4] [PMID: 2932559] 
[65] 
Hortobagyi, G.N.; Theriault, R.L.; Porter, L.; Blayney, D.; Lipton, A.; Sinoff, C.; Wheeler, H.; Simeone, J.F.; Seaman, J.; Knight, R.D. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N. Engl. J. Med.,  1996, 335(24), 1785-1791.
[http://dx.doi.org/10.1056/NEJM199612123352401] [PMID: 8965890] 
[66] 
Rogers, M.J.; Watts, D.J.; Russell, R.G. Overview of bisphosphonates. Cancer,  1997, 80(8)(Suppl.), 1652-1660.
[http://dx.doi.org/10.1002/(SICI)1097-0142(19971015)80:8+<1652:AID-CNCR15>3.0.CO;2-Z] [PMID: 9362432] 
[67] 
Eaton, C.L.; Coleman, R.E. Pathophysiology of bone metastases from prostate cancer and the role of bisphosphonates in treatment. Cancer Treat. Rev.,  2003, 29(3), 189-198.
[http://dx.doi.org/10.1016/S0305-7372(03)00071-9] [PMID: 12787713] 
[68] 
Saad, F.; Gleason, D.M.; Murray, R.; Tchekmedyian, S.; Venner, P.; Lacombe, L.; Chin, J.L.; Vinholes, J.J.; Goas, J.A.; Chen, B. Zoledronic Acid Prostate Cancer Study Group. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J. Natl. Cancer Inst.,  2002, 94(19), 1458-1468.
[http://dx.doi.org/10.1093/jnci/94.19.1458] [PMID: 12359855] 
[69] 
Coleman, R.E.; Seaman, J.J. The role of zoledronic acid in cancer: clinical studies in the treatment and prevention of bone metastases. Semin. Oncol.,  2001, 28(2)(Suppl. 6), 11-16.
[http://dx.doi.org/10.1016/S0093-7754(01)90260-X] [PMID: 11346860] 
[70] 
Lipton, A.; Small, E.; Saad, F.; Gleason, D.; Gordon, D.; Smith, M.; Rosen, L.; Kowalski, M.O.; Reitsma, D.; Seaman, J. The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Invest.,  2002, 20(Suppl. 2), 45-54.
[http://dx.doi.org/10.1081/CNV-120014886] [PMID: 12442349] 
[71] 
Rosen, L.S.; Gordon, D.; Kaminski, M.; Howell, A.; Belch, A.; Mackey, J.; Apffelstaedt, J.; Hussein, M.; Coleman, R.E.; Reitsma, D.J.; Seaman, J.J.; Chen, B.L.; Ambros, Y. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J.,  2001, 7(5), 377-387.
[PMID: 11693896] 
[72] 
Kirby, R.S. Zoledronic acid: a new advance in managing skeletal events in prostate cancer. BJU Int.,  2003, 91(6), 464-465.
[http://dx.doi.org/10.1046/j.1464-410X.2003.04142.x] [PMID: 12656892] 
[73] 
Adami, S. Bisphosphonates in prostate carcinoma. Cancer,  1997, 80(8)(Suppl.), 1674-1679.http://dx.doi.org/10.1002/(SICI)1097-0142(19971015)80: 8+<1674::AID-CNCR18>3.0.CO;2-X
[PMID: 9362435] 
[74] 
Rosen, L.S.; Gordon, D.; Kaminski, M.; Howell, A.; Belch, A.; Mackey, J.; Apffelstaedt, J.; Hussein, M.A.; Coleman, R.E.; Reitsma, D.J.; Chen, B.L.; Seaman, J.J. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer,  2003, 98(8), 1735-1744.
[http://dx.doi.org/10.1002/cncr.11701] [PMID: 14534891] 
[75] 
Rosen, L.S.; Gordon, D.; Tchekmedyian, S.; Yanagihara, R.; Hirsh, V.; Krzakowski, M.; Pawlicki, M.; de Souza, P.; Zheng, M.; Urbanowitz, G.; Reitsma, D.; Seaman, J.J. Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial--the Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group. J. Clin. Oncol.,  2003, 21(16), 3150-3157.
[http://dx.doi.org/10.1200/JCO.2003.04.105] [PMID: 12915606] 
[76] 
Mason, M.D.; Sydes, M.R.; Glaholm, J.; Langley, R.E.; Huddart, R.A.; Sokal, M.; Stott, M.; Robinson, A.C.; James, N.D.; Parmar, M.K.; Dearnaley, D.P. Medical Research Council PR04 Collaborators. Oral sodium clodronate for nonmetastatic prostate cancer--results of a randomized double-blind placebo-controlled trial: Medical Research Council PR04 (ISRCTN61384873). J. Natl. Cancer Inst.,  2007, 99(10), 765-776.
[http://dx.doi.org/10.1093/jnci/djk178] [PMID: 17505072] 
[77] 
Heidenreich, A.; Elert, A.; Hofmann, R. Ibandronate in the treatment of prostate cancer associated painful osseous metastases. Prostate Cancer Prostatic Dis.,  2002, 5(3), 231-235.
[http://dx.doi.org/10.1038/sj.pcan.4500574] [PMID: 12496987] 
[78] 
Weinfurt, K.P.; Anstrom, K.J.; Castel, L.D.; Schulman, K.A.; Saad, F. Effect of zoledronic acid on pain associated with bone metastasis in patients with prostate cancer. Ann. Oncol.,  2006, 17(6), 986-989.
[http://dx.doi.org/10.1093/annonc/mdl041] [PMID: 16533874] 
[79] 
Senaratne, S.G.; Colston, K.W. Direct effects of bisphosphonates on breast cancer cells. Breast Cancer Res.,  2002, 4(1), 18-23.
[http://dx.doi.org/10.1186/bcr412] [PMID: 11879555] 
[80] 
Hoskin, P.J. Bisphosphonates and radiation therapy for palliation of metastatic bone disease. Cancer Treat. Rev.,  2003, 29(4), 321-327.
[http://dx.doi.org/10.1016/S0305-7372(03)00013-6] [PMID: 12927572] 
[81] 
Lin, A.; Ray, M.E. Targeted and systemic radiotherapy in the treatment of bone metastasis. Cancer Metastasis Rev.,  2006, 25(4), 669-675.
[http://dx.doi.org/10.1007/s10555-006-9025-z] [PMID: 17160556] 
[82] 
Hartsell, W.F.; Scott, C.B.; Bruner, D.W.; Scarantino, C.W.; Ivker, R.A.; Roach, M., III; Suh, J.H.; Demas, W.F.; Movsas, B.; Petersen, I.A.; Konski, A.A.; Cleeland, C.S.; Janjan, N.A.; DeSilvio, M. Randomized trial of short- versus long-course radiotherapy for palliation of painful bone metastases. J. Natl. Cancer Inst.,  2005, 97(11), 798-804.
[http://dx.doi.org/10.1093/jnci/dji139] [PMID: 15928300] 
[83] 
Steenland, E.; Leer, J.W.; van Houwelingen, H.; Post, W.J.; van den Hout, W.B.; Kievit, J.; de Haes, H.; Martijn, H.; Oei, B.; Vonk, E.; van der Steen-Banasik, E.; Wiggenraad, R.G.; Hoogenhout, J.; Wárlám-Rodenhuis, C.; van Tienhoven, G.; Wanders, R.; Pomp, J.; van Reijn, M.; van Mierlo, I.; Rutten, E. The effect of a single fraction compared to multiple fractions on painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiother. Oncol.,  1999, 52(2), 101-109.
[http://dx.doi.org/10.1016/S0167-8140(99)00110-3] [PMID: 10577695] 
[84] 
Foro Arnalot, P.; Fontanals, A.V.; Galcerán, J.C.; Lynd, F.; Latiesas, X.S.; de Dios, N.R.; Castillejo, A.R.; Bassols, M.L.; Galán, J.L.; Conejo, I.M.; López, M.A. Randomized clinical trial with two palliative radiotherapy regimens in painful bone metastases: 30 Gy in 10 fractions compared with 8 Gy in single fraction. Radiother. Oncol.,  2008, 89(2), 150-155.
[http://dx.doi.org/10.1016/j.radonc.2008.05.018] [PMID: 18556080] 
[85] 
Agarawal, J.P.; Swangsilpa, T.; van der Linden, Y.; Rades, D.; Jeremic, B.; Hoskin, P.J. The role of external beam radiotherapy in the management of bone metastases. Clin. Oncol. (R. Coll. Radiol.),  2006, 18(10), 747-760.
[http://dx.doi.org/10.1016/j.clon.2006.09.007] [PMID: 17168210] 
[86] 
Van der Linden, Y.M.; Dijkstra, P.D.; Kroon, H.M.; Lok, J.J.; Noordijk, E.M.; Leer, J.W.; Marijnen, C.A. Comparative analysis of risk factors for pathological fracture with femoral metastases. J. Bone Joint Surg. Br.,  2004, 86(4), 566-573.
[http://dx.doi.org/10.1302/0301-620X.86B4.14703] [PMID: 15174555] 
[87] 
Saarto, T.; Janes, R.; Tenhunen, M.; Kouri, M. Palliative radiotherapy in the treatment of skeletal metastases. Eur. J. Pain,  2002, 6(5), 323-330.
[http://dx.doi.org/10.1016/S1090-3801(02)00028-9] [PMID: 12160506] 
[88] 
McQuay, H.J.; Collins, S.L.; Carroll, D.; Moore, R.A. Radiotherapy for the palliation of painful bone metastases. Cochrane Database Syst. Rev., 2000, (2) CD001793
[http://dx.doi.org/10.1002/14651858.CD001793] [PMID: 10796822] 
[89] 
De Felice, F.; Piccioli, A.; Musio, D.; Tombolini, V. The role of radiation therapy in bone metastases management. Oncotarget,  2017, 8(15), 25691-25699.
[http://dx.doi.org/10.18632/oncotarget.14823] [PMID: 28148890] 
[90] 
Kuban, D.A.; Delbridge, T.; el-Mahdi, A.M.; Schellhammer, P.F. Half-body irradiation for treatment of widely metastatic adenocarcinoma of the prostate. J. Urol.,  1989, 141(3), 572-574.
[http://dx.doi.org/10.1016/S0022-5347(17)40897-4] [PMID: 2465419] 
[91] 
Salazar, O.M.; Rubin, P.; Hendrickson, F.R.; Komaki, R.; Poulter, C.; Newall, J.; Asbell, S.O.; Mohiuddin, M.; Van Ess, J. Single-dose half-body irradiation for palliation of multiple bone metastases from solid tumors. Final Radiation Therapy Oncology Group report. Cancer,  1986, 58(1), 29-36.
[http://dx.doi.org/10.1002/1097-0142(19860701)58:1<29:AID-CNCR2820580107>3.0.CO;2-2] [PMID: 2423225] 
[92] 
Serafini, A.N. Therapy of metastatic bone pain. J. Nucl. Med.,  2001, 42(6), 895-906.
[PMID: 11390554] 
[93] 
Finlay, I.G.; Mason, M.D.; Shelley, M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet Oncol.,  2005, 6(6), 392-400.
[http://dx.doi.org/10.1016/S1470-2045(05)70206-0] [PMID: 15925817] 
[94] 
Pandit-Taskar, N.; Batraki, M.; Divgi, C.R. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J. Nucl. Med.,  2004, 45(8), 1358-1365.
[PMID: 15299062] 
[95] 
Russell, R.G.G.; Xia, Z.; Dunford, J.E.; Oppermann, U.; Kwaasi, A.; Hulley, P.A.; Kavanagh, K.L.; Triffitt, J.T.; Lundy, M.W.; Phipps, R.J.; Barnett, B.L.; Coxon, F.P.; Rogers, M.J.; Watts, N.B.; Ebetino, F.H. Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy. Ann. N. Y. Acad. Sci.,  2007, 1117, 209-257.
[http://dx.doi.org/10.1196/annals.1402.089] [PMID: 18056045] 
[96] 
Rogers, M.J. From molds and macrophages to mevalonate: a decade of progress in understanding the molecular mode of action of bisphosphonates. Calcif. Tissue Int.,  2004, 75(6), 451-461.
[http://dx.doi.org/10.1007/s00223-004-0024-1] [PMID: 15332174] 
[97] 
Ebetino, F.H.; Dansereau, S.M. Bisphosphonate antiresorptive structure-activity relationships. Bisphosphonate on bones,  1995, 139-153.
[98] 
Luckman, S.P.; Coxon, F.P.; Ebetino, F.H.; Russell, R.G.; Rogers, M.J. Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation: evidence from structure-activity relationships in J774 macrophages. J. Bone Miner. Res.,  1998, 13(11), 1668-1678.
[http://dx.doi.org/10.1359/jbmr.1998.13.11.1668] [PMID: 9797474] 
[99] 
van Beek, E.; Hoekstra, M.; van de Ruit, M.; Löwik, C.; Papapoulos, S. Structural requirements for bisphosphonate actions in vitro. J. Bone Miner. Res.,  1994, 9(12), 1875-1882.
[http://dx.doi.org/10.1002/jbmr.5650091206] [PMID: 7872052] 
[100] 
Russell, R.G.; Rogers, M.J.; Frith, J.C.; Luckman, S.P.; Coxon, F.P.; Benford, H.L.; Croucher, P.I.; Shipman, C.; Fleisch, H.A. The pharmacology of bisphosphonates and new insights into their mechanisms of action. J. Bone Miner. Res.,  1999, 14(Suppl. 2), 53-65.
[http://dx.doi.org/10.1002/jbmr.5650140212] [PMID: 10510215] 
[101] 
Nancollas, G.H.; Tang, R.; Phipps, R.J.; Henneman, Z.; Gulde, S.; Wu, W.; Mangood, A.; Russell, R.G.; Ebetino, F.H. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone,  2006, 38(5), 617-627.
[http://dx.doi.org/10.1016/j.bone.2005.05.003] [PMID: 16046206] 
[102] 
Dominguez, L.J.; Di Bella, G.; Belvedere, M.; Barbagallo, M. Physiology of the aging bone and mechanisms of action of bisphosphonates. Biogerontology,  2011, 12(5), 397-408.
[http://dx.doi.org/10.1007/s10522-011-9344-5] [PMID: 21695491] 
[103] 
Ikebe, T. Pathophysiology of BRONJ: Drug-related osteoclastic disease of the jaw. Oral Sci. Int.,  2013, 10(1), 1-8.
[http://dx.doi.org/10.1016/S1348-8643(12)00045-6] 
[104] 
Marx, R.E. Oral and intravenous bisphosphonate-induced osteonecrosis of the jaws: history, eitiology, prevention and treatment, 2nd ed; , 2007. 
[105] 
Ebetino, F.H.; Hogan, A.M.; Sun, S.; Tsoumpra, M.K.; Duan, X.; Triffitt, J.T.; Kwaasi, A.A.; Dunford, J.E.; Barnett, B.L.; Oppermann, U.; Lundy, M.W.; Boyde, A.; Kashemirov, B.A.; McKenna, C.E.; Russell, R.G. The relationship between the chemistry and biological activity of the bisphosphonates. Bone,  2011, 49(1), 20-33.
[http://dx.doi.org/10.1016/j.bone.2011.03.774] [PMID: 21497677] 
[106] 
Cremers, S.; Papapoulos, S. Pharmacology of bisphosphonates. Bone,  2011, 49(1), 42-49.
[http://dx.doi.org/10.1016/j.bone.2011.01.014] [PMID: 21281748] 
[107] 
Drake, M.T.; Cremers, S.C. Bisphosphonate therapeutics in bone disease: the hard and soft data on osteoclast inhibition. Mol. Interv.,  2010, 10(3), 141-152.
[http://dx.doi.org/10.1124/mi.10.3.5] [PMID: 20539033] 
[108] 
Cheng, A.; Mavrokokki, A.; Carter, G.; Stein, B.; Fazzalari, N.L.; Wilson, D.F.; Goss, A.N. The dental implications of bisphosphonates and bone disease. Aust. Dent. J.,  2005, 50(4)(Suppl. 2), S4-S13.
[http://dx.doi.org/10.1111/j.1834-7819.2005.tb00384.x] [PMID: 16416712] 
[109] 
Thompson, K.; Rogers, M.J.; Coxon, F.P.; Crockett, J.C. Cytosolic entry of bisphosphonate drugs requires acidification of vesicles after fluid-phase endocytosis. Mol. Pharmacol.,  2006, 69(5), 1624-1632.
[http://dx.doi.org/10.1124/mol.105.020776] [PMID: 16501031] 
[110] 
Lewington, V.J. Bone-seeking radionuclides for therapy. J. Nucl. Med.,  2005, 46(Suppl. 1), 38S-47S.
[PMID: 15653650] 
[111] 
Silberstein, E.B. Teletherapy and radiopharmaceutical therapy of painful bone metastases. Semin. Nucl. Med.,  2005, 35(2), 152-158.
[http://dx.doi.org/10.1053/j.semnuclmed.2004.11.006] [PMID: 15765378] 
[112] 
Silberstein, E.B.; Elgazzar, A.H.; Kapilivsky, A. Phosphorus-32 radiopharmaceuticals for the treatment of painful osseous metastases. Semin. Nucl. Med.,  1992, 22(1), 17-27.
[http://dx.doi.org/10.1016/S0001-2998(05)80153-9] [PMID: 1589802] 
[113] 
Siberstein, E.B. Advances in our understanding of the treatment of painful bone metastasis. J. Nucl. Med.,  2000, 41(4), 655-657.
[PMID: 10809605] 
[114] 
Silberstein, E.B. Systemic radiopharmaceutical therapy of painful osteoblastic metastases. Semin. Radiat. Oncol.,  2000, 10(3), 240-249.
[http://dx.doi.org/10.1053/srao.2000.6592] [PMID: 11034634] 
[115] 
Nair, N. Relative efficacy of 32P and 89Sr in palliation in skeletal metastases. J. Nucl. Med.,  1999, 40(2), 256-261.
[PMID: 10025832] 
[116] 
Shah Syed, G.M.; Maken, R.N.; Muzzaffar, N.; Shah, M.A.; Rana, F. Effective and economical option for pain palliation in prostate cancer with skeletal metastases: 32P therapy revisited. Nucl. Med. Commun.,  1999, 20(8), 697-702.
[http://dx.doi.org/10.1097/00006231-199908000-00003] [PMID: 10451877] 
[117] 
Krishnamurthy, G.T.; Krishnamurthy, S. Radionuclides for metastatic bone pain palliation: a need for rational re-evaluation in the new millennium. J. Nucl. Med.,  2000, 41(4), 688-691.
[PMID: 10768570] 
[118] 
Taylor, A.J., Jr Strontium-89 for the palliation of bone pain due to metastatic disease. J. Nucl. Med.,  1994, 35(12), 2054.
[PMID: 7527458] 
[119] 
Li, W.B.; Höllriegl, V.; Roth, P.; Oeh, U. Influence of human biokinetics of strontium on internal ingestion dose of 90Sr and absorbed dose of 89Sr to organs and metastases. Radiat. Environ. Biophys.,  2008, 47(2), 225-239.
[http://dx.doi.org/10.1007/s00411-007-0154-8] [PMID: 18204850] 
[120] 
Blake, G.M.; Zivanovic, M.A.; Blaquiere, R.M.; Fine, D.R.; McEwan, A.J.; Ackery, D.M. Strontium-89 therapy: measurement of absorbed dose to skeletal metastases. J. Nucl. Med.,  1988, 29(4), 549-557.
[PMID: 3351609] 
[121] 
Blake, G.M.; Zivanovic, M.A.; McEwan, A.J.; Ackery, D.M. Sr-89 therapy: strontium kinetics in disseminated carcinoma of the prostate. Eur. J. Nucl. Med.,  1986, 12(9), 447-454.
[http://dx.doi.org/10.1007/BF00254749] [PMID: 3102236] 
[122] 
Lam, M.G.; de Klerk, J.M.; van Rijk, P.P.; Zonnenberg, B.A. Bone seeking radiopharmaceuticals for palliation of pain in cancer patients with osseous metastases. Anticancer. Agents Med. Chem.,  2007, 7(4), 381-397.
[http://dx.doi.org/10.2174/187152007781058596] [PMID: 17630915] 
[123] 
Ben-Josef, E.; Maughan, R.L.; Vasan, S.; Porter, A.T. A direct measurement of strontium-89 activity in bone metastases. Nucl. Med. Commun.,  1995, 16(6), 452-456.
[http://dx.doi.org/10.1097/00006231-199506000-00006] [PMID: 7675358] 
[124] 
Breen, S.L.; Powe, J.E.; Porter, A.T. Dose estimation in strontium-89 radiotherapy of metastatic prostatic carcinoma. J. Nucl. Med.,  1992, 33(7), 1316-1323.
[PMID: 1613572] 
[125] 
Laing, A.H.; Ackery, D.M. Bayly. R.J.; Buchanan, R.B.; Lewington, V.J.; McEwan, A.J.B.; Macleod, P.M.; Zivanovic M.A. Strontium-89 therapy for pain palliation in prostatic skeletal malignancy. Br. J. Radiol.,  1991, 64, 816-822.
[http://dx.doi.org/10.1259/0007-1285-64-765-816] [PMID: 1717094] 
[126] 
Anderson, P. Samarium for osteoblastic bone metastases and osteosarcoma. Expert Opin. Pharmacother.,  2006, 7(11), 1475-1486.
[http://dx.doi.org/10.1517/14656566.7.11.1475] [PMID: 16859431] 
[127] 
Anderson, P.; Nuñez, R. Samarium lexidronam (153Sm-EDTMP): skeletal radiation for osteoblastic bone metastases and osteosarcoma. Expert Rev. Anticancer Ther.,  2007, 7(11), 1517-1527.
[http://dx.doi.org/10.1586/14737140.7.11.1517] [PMID: 18020921] 
[128] 
Farhanghi, M.; Holmes, R.A.; Volkert, W.A.; Logan, K.W.; Singh, A. Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer. J. Nucl. Med.,  1992, 33(8), 1451-1458.
[PMID: 1378887] 
[129] 
Goeckeler, W.F.; Edwards, B.; Volkert, W.A.; Holmes, R.A.; Simon, J.; Wilson, D. Skeletal localization of samarium-153 chelates: potential therapeutic bone agents. J. Nucl. Med.,  1987, 28(4), 495-504.
[PMID: 3572535] 
[130] 
Singh, A.; Holmes, R.A.; Farhangi, M.; Volkert, W.A.; Williams, A.; Stringham, L.M.; Ketring, A.R. Human pharmacokinetics of samarium-153 EDTMP in metastatic cancer. J. Nucl. Med.,  1989, 30(11), 1814-1818.
[PMID: 2478681] 
[131] 
Wilky, B.A.; Loeb, D.M. Beyond Palliation: Therapeutic Applications of 153Samarium-EDTMP. Clin. Exp. Pharmacol.,  2013, 3(3) 1000131
[http://dx.doi.org/10.4172/2161-1459.1000131] [PMID: 25664221] 
[132] 
Paes, F.M.; Serafini, A.N. Systemic metabolic radiopharmaceutical therapy in the treatment of metastatic bone pain. Semin. Nucl. Med.,  2010, 40(2), 89-104.
[http://dx.doi.org/10.1053/j.semnuclmed.2009.10.003] [PMID: 20113678] 
[133] 
Atkins, H.L.; Mausner, L.F.; Srivastava, S.C.; Meinken, G.E.; Straub, R.F.; Cabahug, C.J.; Weber, D.A.; Wong, C.T.; Sacker, D.F.; Madajewicz, S. Biodistribution of Sn-117m(4+)DTPA for palliative therapy of painful osseous metastases. Radiology,  1993, 186(1), 279-283.
[http://dx.doi.org/10.1148/radiology.186.1.7677974] [PMID: 7677974] 
[134] 
Turner, J.H.; Claringbold, P.G. A phase II study of treatment of painful multifocal skeletal metastases with single and repeated dose samarium-153 ethylenediaminetetramethylene phosphonate. Eur. J. Cancer,  1991, 27(9), 1084-1086.
[http://dx.doi.org/10.1016/0277-5379(91)90297-Q] [PMID: 1720321] 
[135] 
Eary, J.F.; Collins, C.; Stabin, M.; Vernon, C.; Petersdorf, S.; Baker, M.; Hartnett, S.; Ferency, S.; Addison, S.J.; Appelbaum, F. Samarium-153-EDTMP biodistribution and dosimetry estimation. J. Nucl. Med.,  1993, 34(7), 1031-1036.
[PMID: 7686217] 
[136] 
Turner, J.H.; Claringbold, P.G.; Hetherington, E.L.; Sorby, P.; Martindale, A.A. A phase I study of samarium-153 ethylenediaminetetramethylene phosphonate therapy for disseminated skeletal metastases. J. Clin. Oncol.,  1989, 7(12), 1926-1931.
[http://dx.doi.org/10.1200/JCO.1989.7.12.1926] [PMID: 2585026] 
[137] 
Collins, C.; Eary, J.F.; Donaldson, G.; Vernon, C.; Bush, N.E.; Petersdorf, S.; Livingston, R.B.; Gordon, E.E.; Chapman, C.R.; Appelbaum, F.R. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial. J. Nucl. Med.,  1993, 34(11), 1839-1844.
[PMID: 8229221] 
[138] 
Anderson, P.M.; Wiseman, G.A.; Dispenzieri, A.; Arndt, C.A.; Hartmann, L.C.; Smithson, W.A.; Mullan, B.P.; Bruland, O.S. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J. Clin. Oncol.,  2002, 20(1), 189-196.
[http://dx.doi.org/10.1200/JCO.2002.20.1.189] [PMID: 11773169] 
[139] 
Enrique, O.; Zhongyun, P.; Parma, E.P.; Pusuwan, P.; Riccabona, G.; Tian, J.H.; Obaldo, J.; Padhy, A.K. Efficacy and toxicity of Sm-153 EDTMP in the palliative treatment of painful bone metastases. World J. Nucl. Med.,  2002, 1(1), 21-27.
[140] 
Alberts, A.S.; Smit, B.J.; Louw, W.K.; van Rensburg, A.J.; van Beek, A.; Kritzinger, V.; Nel, J.S. Dose response relationship and multiple dose efficacy and toxicity of samarium-153-EDTMP in metastatic cancer to bone. Radiother. Oncol.,  1997, 43(2), 175-179.
[http://dx.doi.org/10.1016/S0167-8140(97)01912-9] [PMID: 9192964] 
[141] 
Resche, I.; Chatal, J.F.; Pecking, A.; Ell, P.; Duchesne, G.; Rubens, R.; Fogelman, I.; Houston, S.; Fauser, A.; Fischer, M.; Wilkins, D. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur. J. Cancer,  1997, 33(10), 1583-1591.
[http://dx.doi.org/10.1016/S0959-8049(97)00155-X] [PMID: 9389919] 
[142] 
Henriksen, G.; Fisher, D.R.; Roeske, J.C.; Bruland, O.S.; Larsen, R.H. Targeting of osseous sites with alpha-emitting 223Ra: comparison with the beta-emitter 89Sr in mice. J. Nucl. Med.,  2003, 44(2), 252-259.
[PMID: 12571218] 
[143] 
Nilsson, S.; Larsen, R.H.; Fosså, S.D.; Balteskard, L.; Borch, K.W.; Westlin, J.E.; Salberg, G.; Bruland, O.S. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin. Cancer Res.,  2005, 11(12), 4451-4459.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-2244] [PMID: 15958630] 
[144] 
Pandit-Taskar, N.; Larson, S.M.; Carrasquillo, J.A. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride. J. Nucl. Med.,  2014, 55(2), 268-274.
[http://dx.doi.org/10.2967/jnumed.112.112482] [PMID: 24343987] 
[145] 
Henriksen, G.; Breistøl, K.; Bruland, O.S.; Fodstad, Ø.; Larsen, R.H. Significant antitumor effect from bone-seeking, alpha-particle-emitting (223)Ra demonstrated in an experimental skeletal metastases model. Cancer Res.,  2002, 62(11), 3120-3125.
[PMID: 12036923] 
[146] 
Liepe, K. Alpharadin, a 223Ra-based alpha-particle-emitting pharmaceutical for the treatment of bone metastases in patients with cancer. Curr. Opin. Investig. Drugs,  2009, 10(12), 1346-1358.
[PMID: 19943206] 
[147] 
McDevitt, M.R.; Sgouros, G.; Finn, R.D.; Humm, J.L.; Jurcic, J.G.; Larson, S.M.; Scheinberg, D.A. Radioimmunotherapy with alpha-emitting nuclides. Eur. J. Nucl. Med.,  1998, 25(9), 1341-1351.
[http://dx.doi.org/10.1007/s002590050306] [PMID: 9724387] 
[148] 
Baidoo, K.E.; Yong, K.; Brechbiel, M.W. Molecular pathways: targeted α-particle radiation therapy. Clin. Cancer Res.,  2013, 19(3), 530-537.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0298] [PMID: 23230321] 
[149] 
Bruland, Ø.S.; Nilsson, S.; Fisher, D.R.; Larsen, R.H. High-linear energy transfer irradiation targeted to skeletal metastases by the alpha-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin. Cancer Res.,  2006, 12(20 Pt 2), 6250s-6257s.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-0841] [PMID: 17062709] 
[150] 
Borsò, E.; Boni, G.; Galli, L.; Ricci, S.; Farnesi, A.; Mazzarri, S.; Cianci, C.; Mariani, G.; Falcone, A. Radium 223 dichloride: a multidisciplinary approach to metastatic castration-resistant prostate cancer. Future Oncol.,  2015, 11(2), 323-331.
[http://dx.doi.org/10.2217/fon.14.157] [PMID: 25075962] 
[151] 
Brady, D.; Parker, C.C.; O’Sullivan, J.M. Bone-targeting radiopharmaceuticals including radium-223. Cancer J.,  2013, 19(1), 71-78.
[http://dx.doi.org/10.1097/PPO.0b013e318282479b] [PMID: 23337760] 
[152] 
Elgqvist, J.; Frost, S.; Pouget, J-P.; Albertsson, P. The potential and hurdles of targeted alpha therapy - clinical trials and beyond. Front. Oncol.,  2014, 3, 324.
[http://dx.doi.org/10.3389/fonc.2013.00324] [PMID: 24459634] 
[153] 
Nilsson, S.; Franzén, L.; Parker, C.; Tyrrell, C.; Blom, R.; Tennvall, J.; Lennernäs, B.; Petersson, U.; Johannessen, D.C.; Sokal, M.; Pigott, K.; O’Bryan-Tear, C.G.; Thuresson, M.; Bolstad, B.; Bruland, Ø.S. Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases. Clin. Genitourin. Cancer,  2013, 11(1), 20-26.
[http://dx.doi.org/10.1016/j.clgc.2012.07.002] [PMID: 23021204] 
[154] 
Sartor, O.; Coleman, R.; Nilsson, S.; Heinrich, D.; Helle, S.I.; O’Sullivan, J.M.; Fosså, S.D.; Chodacki, A.; Wiechno, P.; Logue, J.; Widmark, A.; Johannessen, D.C.; Hoskin, P.; James, N.D.; Solberg, A.; Syndikus, I.; Vogelzang, N.J.; O’Bryan-Tear, C.G.; Shan, M.; Bruland, Ø.S.; Parker, C. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol.,  2014, 15(7), 738-746.
[http://dx.doi.org/10.1016/S1470-2045(14)70183-4] [PMID: 24836273] 
[155] 
Parker, C.; Nilsson, S.; Heinrich, D.; Helle, S.I.; O’Sullivan, J.M.; Fosså, S.D.; Chodacki, A.; Wiechno, P.; Logue, J.; Seke, M.; Widmark, A.; Johannessen, D.C.; Hoskin, P.; Bottomley, D.; James, N.D.; Solberg, A.; Syndikus, I.; Kliment, J.; Wedel, S.; Boehmer, S.; Dall’Oglio, M.; Franzén, L.; Coleman, R.; Vogelzang, N.J.; O’Bryan-Tear, C.G.; Staudacher, K.; Garcia-Vargas, J.; Shan, M.; Bruland, Ø.S.; Sartor, O. ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N. Engl. J. Med.,  2013, 369(3), 213-223.
[http://dx.doi.org/10.1056/NEJMoa1213755] [PMID: 23863050] 
[156] 
Franken, N.A.; Hovingh, S.; Ten Cate, R.; Krawczyk, P.; Stap, J.; Hoebe, R.; Aten, J.; Barendsen, G.W. Relative biological effectiveness of high linear energy transfer α-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells. Oncol. Rep.,  2012, 27(3), 769-774.
[http://dx.doi.org/10.3892/or.2011.1604] [PMID: 22200791] 
[157] 
Ma, N.Y.; Tinganelli, W.; Maier, A.; Durante, M.; Kraft-Weyrather, W. Influence of chronic hypoxia and radiation quality on cell survival. J. Radiat. Res. (Tokyo),  2013, 54(Suppl. 1), i13-i22.
[http://dx.doi.org/10.1093/jrr/rrs135] [PMID: 23824117] 
[158] 
Sgouros, G.; Roeske, J.C.; McDevitt, M.R.; Palm, S.; Allen, B.J. Fisher; D.R.; Brill, A.B.; Song, H.; Howell, R.W.; Akabani, G.; SNM MIRD Committee; Bolch, W.E.; Brill, A.B.; Fisher, D.R.; Howell, R.W.; Meredith, R.F.; Sgouros, G.; Wessels, B.W.; Zanzonico, P.B. MIRD Pamphlet No. 22 (abridged): radiobiology and dosimetry of alphaparticle emitters for targeted radionuclide therapy. J. Nucl. Med.,  2010, 51, 311-328.
[http://dx.doi.org/10.2967/jnumed.108.058651] [PMID: 20080889] 
[159] 
Gadbois, D.M.; Crissman, H.A.; Nastasi, A.; Habbersett, R.; Wang, S.K.; Chen, D.; Lehnert, B.E. Alterations in the progression of cells through the cell cycle after exposure to alpha particles or gamma rays. Radiat. Res.,  1996, 146(4), 414-424.
[http://dx.doi.org/10.2307/3579303] [PMID: 8927713] 
[160] 
Hall, E.J. Radiobiology for the Radiologist, 4th ed; , 1994. 
[161] 
Carrasquillo, J.A.; O’Donoghue, J.A.; Pandit-Taskar, N.; Humm, J.L.; Rathkopf, D.E.; Slovin, S.F.; Williamson, M.J.; Lacuna, K.; Aksnes, A.K.; Larson, S.M.; Scher, H.I.; Morris, M.J. Phase I pharmacokinetic and biodistribution study with escalating doses of 223Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur. J. Nucl. Med. Mol. Imaging,  2013, 40(9), 1384-1393.
[http://dx.doi.org/10.1007/s00259-013-2427-6] [PMID: 23653243] 
[162] 
Lassmann, M.; Nosske, D. Dosimetry of 223Ra-chloride: dose to normal organs and tissues. Eur. J. Nucl. Med. Mol. Imaging,  2013, 40(2), 207-212.
[http://dx.doi.org/10.1007/s00259-012-2265-y] [PMID: 23053328] 
[163] 
Kluetz, P.G.; Pierce, W.; Maher, V.E.; Zhang, H.; Tang, S.; Song, P.; Liu, Q.; Haber, M.T.; Leutzinger, E.E.; Al-Hakim, A.; Chen, W.; Palmby, T.; Alebachew, E.; Sridhara, R.; Ibrahim, A.; Justice, R.; Pazdur, R. Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary. Clin. Cancer Res.,  2014, 20(1), 9-14.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2665] [PMID: 24190979] 
[164] 
Mohler, J.L.; Kantoff, P.W.; Armstrong, A.J.; Bahnson, R.R.; Cohen, M.; D’Amico, A.V.; Eastham, J.A.; Enke, C.A.; Farrington, T.A.; Higano, C.S.; Horwitz, E.M.; Kawachi, M.H.; Kuettel, M.; Lee, R.J.; Macvicar, G.R.; Malcolm, A.W.; Miller, D.; Plimack, E.R.; Pow-Sang, J.M.; Richey, S.; Roach, M., III; Rohren, E.; Rosenfeld, S.; Small, E.J.; Srinivas, S.; Stein, C.; Strope, S.A.; Tward, J.; Walsh, P.C.; Shead, D.A.; Ho, M. National comprehensive cancer network. Prostate cancer, version 1.2014. J. Natl. Compr. Canc. Netw.,  2013, 11(12), 1471-1479.
[http://dx.doi.org/10.6004/jnccn.2013.0174] [PMID: 24335682] 
[165] 
Nilsson, S.; Franzén, L.; Parker, C.; Tyrrell, C.; Blom, R.; Tennvall, J.; Lennernäs, B.; Petersson, U.; Johannessen, D.C.; Sokal, M.; Pigott, K.; Yachnin, J.; Garkavij, M.; Strang, P.; Harmenberg, J.; Bolstad, B.; Bruland, O.S. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol.,  2007, 8(7), 587-594.
[http://dx.doi.org/10.1016/S1470-2045(07)70147-X] [PMID: 17544845] 
[166] 
Nilsson, S.; Strang, P.; Aksnes, A.K.; Franzèn, L.; Olivier, P.; Pecking, A.; Staffurth, J.; Vasanthan, S.; Andersson, C.; Bruland, Ø.S. A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur. J. Cancer,  2012, 48(5), 678-686.
[http://dx.doi.org/10.1016/j.ejca.2011.12.023] [PMID: 22341993] 
[167] 
De Klerk, J.M.; Zonnenberg, B.A.; Blijham, G.H.; Van Het Schip, A.D.; Hoekstra, A.; Han, S.H.; Quirijnen, J.M.; Van Dijk, A.; Van Rijk, P.P. Treatment of metastatic bone pain using the bone seeking radiopharmaceutical Re-186-HEDP. Anticancer Res.,  1997, 17(3B), 1773-1777.
[PMID: 9179233] 
[168] 
Maxon, H.R.; Deutsch, E.A.; Thomas, S.R.; Libson, K.; Lukes, S.J.; Williams, C.C.; Ali, S. Re-186(Sn) HEDP for treatment of multiple metastatic foci in bone: human biodistribution and dosimetric studies. Radiology,  1988, 166(2), 501-507.
[http://dx.doi.org/10.1148/radiology.166.2.3122267] [PMID: 3122267] 
[169] 
Maxon, H.R., III; Schroder, L.E.; Thomas, S.R.; Hertzberg, V.S.; Deutsch, E.A.; Scher, H.I.; Samaratunga, R.C.; Libson, K.F.; Williams, C.C.; Moulton, J.S. Re-186(Sn) HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer. Radiology,  1990, 176(1), 155-159.
[http://dx.doi.org/10.1148/radiology.176.1.1693784] [PMID: 1693784] 
[170] 
Quirijnen, J.M.S.P.; Han, S.H.; Zonnenberg, B.A.; de Klerk, J.M.H.; van het Schip, A.D.; van Dijk, A.; ten Kroode, H.F.J.; Blijham, G.H.; van Rijk, P.P. Efficacy of rhenium-186-etidronate in prostate cancer patients with metastatic bone pain. J. Nucl. Med.,  1996, 37(9), 1511-1515.
[PMID: 8790203] 
[171] 
Schoeneich, G.; Palmedo, H.; Dierke-Dzierzon, C.; Müller, S.C.; Biersack, H.J. Rhenium-186 HEDP: palliative radionuclide therapy of painful bone metastases. Preliminary results. Scand. J. Urol. Nephrol.,  1997, 31(5), 445-448.
[http://dx.doi.org/10.3109/00365599709030639] [PMID: 9406304] 
[172] 
Palmedo, H.; Guhlke, S.; Bender, H.; Sartor, J.; Schoeneich, G.; Risse, J.; Grünwald, F.; Knapp, F.F., Jr; Biersack, H.J. Dose escalation study with rhenium-188 hydroxyethylidene diphosphonate in prostate cancer patients with osseous metastases. Eur. J. Nucl. Med.,  2000, 27(2), 123-130.
[http://dx.doi.org/10.1007/s002590050017] [PMID: 10755716] 
[173] 
Mathieu, L.; Chevalier, P.; Galy, G.; Berger, M. Preparation of rhenium-186 labelled EHDP and its possible use in the treatment of osseous neoplasms. Int. J. Appl. Radiat. Isot.,  1979, 30(12), 725-727.
[http://dx.doi.org/10.1016/0020-708X(79)90150-9] [PMID: 118937] 
[174] 
Deutsch, E.; Libson, K.; Vanderheyden, J.L.; Ketring, A.R.; Maxon, H.R. The chemistry of rhenium and technetium as related to the use of isotopes of these elements in therapeutic and diagnostic nuclear medicine. Int. J. Rad. Appl. Instrum. B,  1986, 13(4), 465-477.
[http://dx.doi.org/10.1016/0883-2897(86)90027-9] [PMID: 3793504] 
[175] 
Graham, M.C.; Scher, H.I.; Liu, G.B.; Yeh, S.D.; Curley, T.; Daghighian, F.; Goldsmith, S.J.; Larson, S.M. Rhenium-186-labeled hydroxyethylidene diphosphonate dosimetry and dosing guidelines for the palliation of skeletal metastases from androgen-independent prostate cancer. Clin. Cancer Res.,  1999, 5(6), 1307-1318.
[PMID: 10389913] 
[176] 
Sciuto, R.; Tofani, A.; Festa, A.; Giannarelli, D.; Pasqualoni, R.; Maini, C.L. Short- and long-term effects of 186Re-1,1-hydroxyethylidene diphosphonate in the treatment of painful bone metastases. J. Nucl. Med.,  2000, 41(4), 647-654.
[PMID: 10768566] 
[177] 
Lin, W.; Lin, C.; Yeh, S.; Hsieh, B.T.; Tsai, Z.T.; Ting, G.; Yen, T.C.; Wang, S.J.; Knapp, F.F., Jr; Stabin, M.G. Rhenium-188 HEDP: a new generator-produced radiotherapeutic drug of potential value for treatment of bone metastases. Eur. J. Nucl. Med.,  1997, 24, 590-595.
[http://dx.doi.org/10.1007/BF00841394] [PMID: 9169563] 
[178] 
Sciuto, R.; Festa, A.; Pasqualoni, R.; Semprebene, A.; Rea, S.; Bergomi, S.; Maini, C.L. Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients. Breast Cancer Res. Treat.,  2001, 66(2), 101-109.
[http://dx.doi.org/10.1023/A:1010658522847] [PMID: 11437096] 
[179] 
Dafermou, A.; Colamussi, P.; Giganti, M.; Cittanti, C.; Bestagno, M.; Piffanelli, A. A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur. J. Nucl. Med.,  2001, 28(7), 788-798.
[http://dx.doi.org/10.1007/s002590100533] [PMID: 11504074] 
[180] 
de Klerk, J.M.; van het Schip, A.D.; Zonnenberg, B.A.; van Dijk, A.; Quirijnen, J.M.; Blijham, G.H.; van Rijk, P.P. Phase 1 study of rhenium-186-HEDP in patients with bone metastases originating from breast cancer. J. Nucl. Med.,  1996, 37(2), 244-249.
[PMID: 8667053] 
[181] 
Han, S.H.; de Klerk, J.M.; Tan, S.; van het Schip, A.D.; Derksen, B.H.; van Dijk, A.; Kruitwagen, C.L.; Blijham, G.H.; van Rijk, P.P.; Zonnenberg, B.A. The PLACORHEN study: a double-blind, placebo-controlled, randomized radionuclide study with 186Re-etidronate in hormone-resistant prostate cancer patients with painful bone metastases. Placebo Controlled Rhenium Study. J. Nucl. Med.,  2002, 43(9), 1150-1156.
[PMID: 12215552] 
[182] 
Englaro, E.E.; Schroder, L.E.; Thomas, S.R.; Williams, C.C.; Maxon, H.R., III Safety and efficacy of repeated sequential administrations of Re-186(Sn)HEDP as palliative therapy for painful skeletal metastases. Initial case reports of two patients. Clin. Nucl. Med.,  1992, 17(1), 41-44.
[http://dx.doi.org/10.1097/00003072-199201000-00012] [PMID: 1371956] 
[183] 
Lyra, M.; Phinou, P. Internal dosimetry in nuclear medicine: a summary of its development, applications and current limitations. RSO Magazine,  2000, 5(2), 17-30.
[184] 
Maxon, H.R., III; Schroder, L.E.; Hertzberg, V.S.; Thomas, S.R.; Englaro, E.E.; Samaratunga, R.; Smith, H.; Moulton, J.S.; Williams, C.C.; Ehrhardt, G.J. Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo. J. Nucl. Med.,  1991, 32(10), 1877-1881.
[PMID: 1717669] 
[185] 
Biersack, H.J.; Palmedo, H.; Andris, A.; Rogenhofer, S.; Knapp, F.F.; Guhlke, S.; Ezziddin, S.; Bucerius, J.; von Mallek, D. Palliation and survival after repeated (188)Re-HEDP therapy of hormone-refractory bone metastases of prostate cancer: a retrospective analysis. J. Nucl. Med.,  2011, 52(11), 1721-1726.
[http://dx.doi.org/10.2967/jnumed.111.093674] [PMID: 21976530] 
[186] 
Yasushi, A.; Masahiro, O.; Koji, W.; Takashi, U.; Hiroyuki, A.; Yuji, M.; Akira, Y.; Yasuhiro, M.; Junji, K. Synthesis and biodistribution studies of 186Re complex of 1-hydroxyethylidene-1,1-diphosphonate for treatment of painful osseous metastases. Radioisotopes,  1995, 44, 514-522.
[http://dx.doi.org/10.3769/radioisotopes.44.8_514] 
[187] 
De Winter, F.; Brans, B.; Van De Wiele, C.; Dierckx, R.A. Visualization of the stomach on rhenium-186 HEDP imaging after therapy for metastasized prostate carcinoma. Clin. Nucl. Med.,  1999, 24(11), 898-899.
[http://dx.doi.org/10.1097/00003072-199911000-00022] [PMID: 10551482] 
[188] 
Limouris, G.S.; Skukla, S.K. Gastric uptake during Re-186 HEDP bone scintigraphy. Anticancer Res.,  1997, 17(3B), 1779-1781.
[PMID: 9179234] 
[189] 
de Klerk, J.M.; van Dijk, A.; van het Schip, A.D.; Zonnenberg, B.A.; van Rijk, P.P. Pharmacokinetics of rhenium-186 after administration of rhenium-186-HEDP to patients with bone metastases. J. Nucl. Med.,  1992, 33(5), 646-651.
[PMID: 1373767] 
[190] 
Ogawa, K.; Mukai, T.; Arano, Y.; Otaka, A.; Ueda, M.; Uehara, T.; Magata, Y.; Hashimoto, K.; Saji, H. Rhemium-186-monoaminemonoamidedithiol-conjugated bisphosphonate derivatives for bone pain palliation. Nucl. Med. Biol.,  2006, 33(4), 513-520.
[http://dx.doi.org/10.1016/j.nucmedbio.2006.03.006] [PMID: 16720243] 
[191] 
Ogawa, K.; Mukai, T.; Arano, Y.; Hanaoka, H.; Hashimoto, K.; Nishimura, H.; Saji, H. Design of a radiopharmaceutical for the palliation of painful bone metastases: rhenium-186- labeled bisphosphonate derivative. J. Labelled Comp. Radiopharm.,  2004, 47(11), 753-761.
[http://dx.doi.org/10.1002/jlcr.864] 
[192] 
Ogawa, K.; Mukai, T.; Arano, Y.; Ono, M.; Hanaoka, H.; Ishino, S.; Hashimoto, K.; Nishimura, H.; Saji, H. Development of a rhenium-186-labeled MAG3-conjugated bisphosphonate for the palliation of metastatic bone pain based on the concept of bifunctional radiopharmaceuticals. Bioconjug. Chem.,  2005, 16(4), 751-757.
[http://dx.doi.org/10.1021/bc040249w] [PMID: 16029015] 
[193] 
Uehara, T.; Jin, Z.L.; Ogawa, K.; Akizawa, H.; Hashimoto, K.; Nakayama, M.; Arano, Y. Assessment of 186Re chelate-conjugated bisphosphonate for the development of new radiopharmaceuticals for bones. Nucl. Med. Biol.,  2007, 34(1), 79-87.
[http://dx.doi.org/10.1016/j.nucmedbio.2006.10.001] [PMID: 17210464] 
[194] 
Torres Martin de Rosales, R.; Finucane, C.; Foster, J.; Mather, S.J.; Blower, P.J. 188Re(CO)3-dipicolylamine-alendronate: a new bisphosphonate conjugate for the radiotherapy of bone metastases. Bioconjug. Chem.,  2010, 21(5), 811-815.
[http://dx.doi.org/10.1021/bc100071k] [PMID: 20387897] 
[195] 
Bisunandan, M.; Blower, P.J.; Clarke, S.E.M.; Singh, J.; Went, M.J. Synthesis and characterization of [186Re]Re(V)dimercaptosuccinic acid: a possible tumour imaging radiotherapy agent. Appl. Radiat. Isot.,  1991, 42(2), 167-171.
[http://dx.doi.org/10.1016/0883-2889(91)90068-C] [PMID: 1648035] 
[196] 
Blower, P.J.; Lam, A.S.; O’Doherty, M.J.; Kettle, A.G.; Coakley, A.J.; Knapp, F.F., Jr Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy: synthesis and preliminary animal and human studies. Eur. J. Nucl. Med.,  1998, 25(6), 613-621.
[http://dx.doi.org/10.1007/s002590050263] [PMID: 9618576] 
[197] 
Blower, P.J.; Kettle, A.G.; O’Doherty, M.J.; Coakley, A.J.; Knapp, F.F., Jr 99mTc(V)DMSA quantitatively predicts 188Re(V)DMSA distribution in patients with prostate cancer metastatic to bone. Eur. J. Nucl. Med.,  2000, 27(9), 1405-1409.
[http://dx.doi.org/10.1007/s002590000307] [PMID: 11007525] 
[198] 
Lam, A.S.; Kettle, A.G.; O’Doherty, M.J.; Coakley, A.J.; Barrington, S.F.; Blower, P.J. Pentavalent 99Tcm-DMSA imaging in patients with bone metastases. Nucl. Med. Commun.,  1997, 18(10), 907-914.
[http://dx.doi.org/10.1097/00006231-199710000-00003] [PMID: 9392790] 
[199] 
Singh, J.; Reghebi, K.; Lazarus, C.R.; Clarke, S.E.; Callahan, A.P.; Knapp, F.F., Jr; Blower, P.J. Studies on the preparation and isomeric composition of 186Re- and 188Re-pentavalent rhenium dimercaptosuccinic acid complex. Nucl. Med. Commun.,  1993, 14(3), 197-203.
[http://dx.doi.org/10.1097/00006231-199303000-00009] [PMID: 8384352] 
[200] 
Pirmettis, I.; Limouris, G.S.; Bouziotis, P.; Papadopolous, M.; Knapp, F.F., Jr; Chiotellis, E. Pentavalent Rhenium-188 dimercaptosuccinic acid: a new kit formulation and its initial evaluation in mice. Radiochim. Acta,  2001, 89, 115-118.
[http://dx.doi.org/10.1524/ract.2001.89.2.115] 
[201] 
Guhlke, S.; Scheithauer, S.; Oetjen, K.; Sartor, J.; Bender, H.; Biersack, H.J. 188Re(V)-DMSA: in-vitro and in-vivo studies on the individual stereo isomers. Radiochim. Acta,  2004, 92, 277-283.
[http://dx.doi.org/10.1524/ract.92.4.277.35610] 
[202] 
Li, S.; Liu, J.; Zhang, H.; Tian, M.; Wang, J.; Zheng, X. Rhenium-188 HEDP to treat painful bone metastases. Clin. Nucl. Med.,  2001, 26(11), 919-922.
[http://dx.doi.org/10.1097/00003072-200111000-00006] [PMID: 11595844] 
[203] 
Oh, S.J.; Won, K.S.; Moon, D.H.; Cheon, J.H.; Ha, H.J.; Jeong, J.M.; Lee, H.K. Preparation and biological evaluation of 188Re-ethylenediamine-N,N,N′,N′-tetrakis(methylene phosphonic acid) as a potential agent for bone pain palliation. Nucl. Med. Commun.,  2002, 23(1), 75-81.
[http://dx.doi.org/10.1097/00006231-200201000-00012] [PMID: 11748441] 
[204] 
Lisic, E.C.; Phillips, M.; Ensor, D.; Nash, K.L.; Beets, A.; Knapp, F.F. Synthesis of a new bisphosphonic acid ligand (SEDP) and preparation of a 188Re-(Sn)SEDP bone seeking radiotracer. Nucl. Med. Biol.,  2001, 28(4), 419-424.
[http://dx.doi.org/10.1016/S0969-8051(00)00205-5] [PMID: 11395315] 
[205] 
Hsieh, B.T.; Hsieh, J.F.; Tsai, S.C.; Lin, W.Y.; Wang, S.J.; Ting, G. Comparison of various rhenium-188-labeled diphosphonates for the treatment of bone metastases. Nucl. Med. Biol.,  1999, 26(8), 973-976.
[http://dx.doi.org/10.1016/S0969-8051(99)00075-X] [PMID: 10708313] 
[206] 
Lin, W.Y.; Lin, C.P.; Yeh, S.J.; Hsieh, B.T.; Tsai, Z.T.; Ting, G.; Yen, T.C.; Wang, S.J.; Knapp, F.F., Jr; Stabin, M.G. Rhenium-188 hydroxyethylidene diphosphonate: a new generator-produced radiotherapeutic drug of potential value for the treatment of bone metastases. Eur. J. Nucl. Med.,  1997, 24(6), 590-595.
[http://dx.doi.org/10.1007/BF00841394] [PMID: 9169563] 
[207] 
Orsini, F.; Guidoccio, F.; Mazzarri, S.; Mariani, G. Palliation and survival after repeated 188Re-HEDP therapy of hormone-refractory bone metastases of prostate cancer: a retrospective analysis. J. Nucl. Med.,  2012, 53(8), 1330-1331.
[http://dx.doi.org/10.2967/jnumed.112.104943] [PMID: 22717979] 
[208] 
Palmedo, H.; Manka-Waluch, A.; Albers, P.; Schmidt-Wolf, I.G.; Reinhardt, M.; Ezziddin, S.; Joe, A.; Roedel, R.; Fimmers, R.; Knapp, F.F., Jr; Guhlke, S.; Biersack, H.J. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J. Clin. Oncol.,  2003, 21(15), 2869-2875.
[http://dx.doi.org/10.1200/JCO.2003.12.060] [PMID: 12885803] 
[209] 
Lange, R.; Ter Heine, R.; van der Gronde, T.; Selles, S.; de Klerk, J.; Bloemendal, H.; Hendrikse, H. Applying quality by design principles to the small-scale preparation of the bone-targeting therapeutic radiopharmaceutical rhenium-188-HEDP. Eur. J. Pharm. Sci.,  2016, 90, 96-101.
[http://dx.doi.org/10.1016/j.ejps.2016.01.008] [PMID: 26772897] 
[210] 
Khalaf, F.; Dogan, A.S.; Haslerud, T.; Sabet, A.; Biersack, H.J.; Ezziddin, S. Liver and lymph node metastases of prostate cancer visualized on post-therapy imaging after treatment with 188Re-HEDP. Rev. Esp. Med. Nucl. Imagen Mol.,  2014, 33(1), 58-59.
[http://dx.doi.org/10.1016/j.remn.2013.04.003] [PMID: 23727275] 
[211] 
Lambert, B.; de Klerk, J.M. Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy. Nucl. Med. Commun.,  2006, 27(3), 223-229.
[http://dx.doi.org/10.1097/00006231-200603000-00004] [PMID: 16479241] 
[212] 
Zhang, H.; Tian, M.; Li, S.; Liu, J.; Tanada, S.; Endo, K. Rhenium-188-HEDP therapy for the palliation of pain due to osseous metastases in lung cancer patients. Cancer Biother. Radiopharm.,  2003, 18(5), 719-726.
[http://dx.doi.org/10.1089/108497803770418265] [PMID: 14629820] 
[213] 
Savio, E.; Gaudiano, J.; Robles, A.M.; Balter, H.; Paolino, A.; López, A.; Hermida, J.C.; De Marco, E.; Martinez, G.; Osinaga, E.; Knapp, F.F., Jr Re-HEDP : pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose. BMC Nucl. Med.,  2001, 1(1), 2.
[http://dx.doi.org/10.1186/1471-2385-1-2] [PMID: 11734069] 
[214] 
Liepe, K.; Hliscs, R.; Kropp, J.; Grüning, T.; Runge, R.; Koch, R.; Knapp, F.F., Jr; Franke, W.G. Rhenium-188-HEDP in the palliative treatment of bone metastases. Cancer Biother. Radiopharm.,  2000, 15(3), 261-265.
[http://dx.doi.org/10.1089/108497800414356] [PMID: 10941533] 
[215] 
Jong, J.M.; Oprea-Lager, D.E.; Hooft, L.; de Klerk, J.M.; Bloemendal, H.J.; Verheul, H.M.; Hoekstra, O.S.; van den Eertwegh, A.J. Radiopharmaceuticals for palliation of bone pain in patients with castration-resistant prostate cancer metastatic to bone: a systematic review. Eur. Urol.,  2016, 70(3), 416-426.
[http://dx.doi.org/10.1016/j.eururo.2015.09.005] [PMID: 26391636] 
[216] 
Liepe, K.; Hliscs, R.; Kropp, J.; Runge, R.; Knapp, F.F., Jr; Franke, W.G. Dosimetry of 188Re-hydroxyethylidene diphosphonate in human prostate cancer skeletal metastases. J. Nucl. Med.,  2003, 44(6), 953-960.
[PMID: 12791825] 
[217] 
Chen, S.L. Treatment of metastatic bone pain with 188Re- HEDP. J. Nucl. Med.,  2000, 5(Suppl.), 265.
[218] 
Liepe, K.; Kropp, J.; Runge, R.; Kotzerke, J. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br. J. Cancer,  2003, 89(4), 625-629.
[http://dx.doi.org/10.1038/sj.bjc.6601158] [PMID: 12915868] 
[219] 
Lam, M.G.E.H.; Bosma, T.B.; van Rijk, P.P.; Zonnenberg, B.A. 188Re-HEDP combined with capecitabine in hormone-refractory prostate cancer patients with bone metastases: a phase I safety and toxicity study. Eur. J. Nucl. Med. Mol. Imaging,  2009, 36(9), 1425-1433.
[http://dx.doi.org/10.1007/s00259-009-1119-8] [PMID: 19319526] 
[220] 
Das, T.; Pillai, M.R.A. Options to meet the future global demand of radionuclides for radionuclide therapy. Nucl. Med. Biol.,  2013, 40(1), 23-32.
[http://dx.doi.org/10.1016/j.nucmedbio.2012.09.007] [PMID: 23116551] 
[221] 
Krishnamurthy, G.T.; Swailem, F.M.; Srivastava, S.C.; Atkins, H.L.; Simpson, L.J.; Walsh, T.K.; Ahmann, F.R.; Meinken, G.E.; Shah, J.H. Tin-117m(4+)DTPA: pharmacokinetics and imaging characteristics in patients with metastatic bone pain. J. Nucl. Med.,  1997, 38(2), 230-237.
[PMID: 9025743] 
[222] 
Bishayee, A.; Rao, D.V.; Srivastava, S.C.; Bouchet, L.G.; Bolch, W.E.; Howell, R.W. Marrow-sparing effects of 117mSn(4+)diethylenetriaminepentaacetic acid for radionuclide therapy of bone cancer. J. Nucl. Med.,  2000, 41(12), 2043-2050.
[PMID: 11138691] 
[223] 
Srivastava, S.C.; Atkins, H.L.; Krishnamurthy, G.T.; Zanzi, I.; Silberstein, E.B.; Meinken, G.; Mausner, L.F.; Swailem, F.; D’Alessandro, T.; Cabahug, C.J.; Lau, Y.; Park, T.; Madajewicz, S. Treatment of metastatic bone pain with tin-117m Stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study. Clin. Cancer Res.,  1998, 4(1), 61-68.
[PMID: 9516953] 
[224] 
Zeevaart, J.R.; Jansen, D.R.; Botelho, M.F.; Abrunhosa, A.; Gomes, C.; Metello, L.; Kolar, Z.I.; Krijger, G.C.; Louw, W.K.A.; Dormehl, I.C. Comparison of the predicted in vivo behaviour of the Sn(II)-APDDMP complex and the results as studied in a rodent model. J. Inorg. Biochem.,  2004, 98(9), 1521-1530.
[http://dx.doi.org/10.1016/j.jinorgbio.2004.06.004] [PMID: 15337604] 
[225] 
Firestone, R. Table of Isotopes; New York, 1996. 
[226] 
Máthé, D.; Balogh, L.; Polyák, A.; Király, R.; Márián, T.; Pawlak, D.; Zaknun, J.J.; Pillai, M.R.A.; Jánoki, G.A. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent. Nucl. Med. Biol.,  2010, 37(2), 215-226.
[http://dx.doi.org/10.1016/j.nucmedbio.2009.09.004] [PMID: 20152721] 
[227] 
Pillai, M.R.A.; Chakraborty, S.; Das, T.; Venkatesh, M.; Ramamoorthy, N. Production logistics of 177Lu for radionuclide therapy. Appl. Radiat. Isot.,  2003, 59(2-3), 109-118.
[http://dx.doi.org/10.1016/S0969-8043(03)00158-1] [PMID: 12941498] 
[228] 
Ando, A.; Ando, I.; Tonami, N.; Kinuya, S.; Kazuma, K.; Kataiwa, A.; Nakagawa, M.; Fujita, N. 177Lu-EDTMP: a potential therapeutic bone agent. Nucl. Med. Commun.,  1998, 19(6), 587-591.
[http://dx.doi.org/10.1097/00006231-199806000-00012] [PMID: 10234664] 
[229] 
Solla, G.A.R.; Arguelles, M.G.; Bottazzini, D.L. Lutetium- 177-EDTMP for bone pain palliation. Preparation, biodistribution and pre-clinical studies. Radiochim. Acta,  2000, 88(3-4), 157-162.
[http://dx.doi.org/10.1524/ract.2000.88.3-4.157] 
[230] 
Garnuszek, P.; Pawlak, D.; Licińska, I.; Kamińska, A. Evaluation of a freeze-dried kit for EDTMP-based bone-seeking radiopharmaceuticals. Appl. Radiat. Isot.,  2003, 58(4), 481-488.
[http://dx.doi.org/10.1016/S0969-8043(03)00057-5] [PMID: 12672628] 
[231] 
Chakraborty, S.; Das, T.; Sarma, H.D.; Venkatesh, M.; Banerjee, S. Comparative studies of 177Lu-EDTMP and 177Lu-DOTMP as potential agents for palliative radiotherapy of bone metastasis. Appl. Radiat. Isot.,  2008, 66(9), 1196-1205.
[http://dx.doi.org/10.1016/j.apradiso.2008.02.061] [PMID: 18372188] 
[232] 
Chakraborty, S.; Das, T.; Banerjee, S.; Balogh, L.; Chaudhari, P.R.; Sarma, H.D.; Polyák, A.; Máthé, D.; Venkatesh, M.; Janoki, G.; Pillai, M.R.A. 177Lu-EDTMP: a viable bone pain palliative in skeletal metastasis. Cancer Biother. Radiopharm.,  2008, 23(2), 202-213.
[http://dx.doi.org/10.1089/cbr.2007.374] [PMID: 18454689] 
[233] 
Yousefnia, H.; Zolghadri, S.; Jalilian, A.R. Absorbed dose assessment of (177)Lu-zoledronate and (177)Lu-EDTMP for human based on biodistribution data in rats. J. Med. Phys.,  2015, 40(2), 102-108.
[http://dx.doi.org/10.4103/0971-6203.158694] [PMID: 26170557] 
[234] 
Balter, H.; Victoria, T.; Mariella, T.; Javier, G.; Rodolfo, F.; Andrea, P.; Graciela, R.; Juan, H.; Eugenia, M.; Patricia, O. 177Lu-labeled agents for neuroendocrine tumor therapy and bone pain palliation in Uruguay. Curr. Radiopharm.,  2016, 9(1), 85-93.
[http://dx.doi.org/10.2174/1874471008666150313112620] [PMID: 25771367] 
[235] 
Chakraborty, S.; Balogh, L.; Das, T.; Polyák, A.; Andócs, G.; Máthé, D.; Király, R.; Thuróczy, J.; Chaudhari, P.R.; Jánoki, G.A.; Jánoki, G.; Banerjee, S.; Pillai, M.R. evaluation of 177Lu-EDTMP in dogs with spontaneous tumor involving bone: pharmacokinetics, dosimetry and therapeutic efficacy. Curr. Radiopharm.,  2016, 9(1), 64-70.
[http://dx.doi.org/10.2174/1874471008666150312164255] [PMID: 25771374] 
[236] 
Pommé, S.; Paepen, J.; Altzitzoglou, T.; Van Ammel, R.; Yeltepe, E. Measurement of the 177Lu half-life. Appl. Radiat. Isot.,  2011, 69(9), 1267-1273.
[http://dx.doi.org/10.1016/j.apradiso.2011.04.021] [PMID: 21550813] 
[237] 
Garske, U.; Sandström, M.; Johansson, S.; Sundin, A.; Granberg, D.; Eriksson, B.; Lundqvist, H. Minor changes in effective half-life during fractionated 177Lu-octreotate therapy. Acta Oncol.,  2012, 51(1), 86-96.
[http://dx.doi.org/10.3109/0284186X.2011.618511] [PMID: 21961497] 
[238] 
Bahrami-Samani, A.; Anvari, A.; Jalilian, A.R.; Shirvani-Arani, S.; Yousefnia, H.; Aghamiri, M.R.; Ghannadi-Maragheh, M. Production, quality control and pharmacokinetic studies of 177Lu-EDTMP for human bone pain palliation therapy trials. Iran. J. Pharm. Res.,  2012, 11(1), 137-144.
[PMID: 25317195] 
[239] 
Sohaib, M.; Ahmad, M.; Jehangir, M.; Perveen, A. Ethylene diamine tetramethylene phosphonic acid labeled with various β(-)-emitting radiometals: labeling optimization and animal biodistribution. Cancer Biother. Radiopharm.,  2011, 26(2), 159-164.
[http://dx.doi.org/10.1089/cbr.2010.0846] [PMID: 21510750] 
[240] 
Yuan, J.; Liu, C.; Liu, X.; Wang, Y.; Kuai, D.; Zhang, G.; Zaknun, J.J. Efficacy and safety of 177Lu-EDTMP in bone metastatic pain palliation in breast cancer and hormone refractory prostate cancer: a phase II study. Clin. Nucl. Med.,  2013, 38(2), 88-92.
[http://dx.doi.org/10.1097/RLU.0b013e318279bf4d] [PMID: 23334120] 
[241] 
Shinto, A.S.; Shibu, D.; Kamaleshwaran, K.K.; Das, T.; Chakraborty, S.; Banerjee, S.; Thirumalaisamy, P.; Das, P.; Veersekar, G. 177Lu-EDTMP for treatment of bone pain in patients with disseminated skeletal metastases. J. Nucl. Med. Technol.,  2014, 42(1), 55-61.
[http://dx.doi.org/10.2967/jnmt.113.132266] [PMID: 24503346] 
[242] 
Bal, C.; Arora, G.; Kumar, P.; Damle, N.; Das, T.; Chakraborty, S.; Banerjee, S.; Venkatesh, M.; Zaknun, J.J.; Pillai, M.R. Pharmacokinetic, dosimetry and toxicity study of 177Lu-EDTMP in patients: phase 0/I study. Curr. Radiopharm.,  2016, 9(1), 71-84.
[http://dx.doi.org/10.2174/1874471008666150313105000] [PMID: 25771371] 
[243] 
Agarwal, K.K.; Singla, S.; Arora, G.; Bal, C. (177)Lu-EDTMP for palliation of pain from bone metastases in patients with prostate and breast cancer: a phase II study. Eur. J. Nucl. Med. Mol. Imaging,  2015, 42(1), 79-88.
[http://dx.doi.org/10.1007/s00259-014-2862-z] [PMID: 25070686] 
[244] 
Thapa, P.; Nikam, D.; Das, T.; Sonawane, G.; Agarwal, J.P.; Basu, S. Clinical efficacy and safety comparison of 177Lu-EDTMP with 153Sm-EDTMP on an equidose basis in patients with painful skeletal metastases. J. Nucl. Med.,  2015, 56(10), 1513-1519.
[http://dx.doi.org/10.2967/jnumed.115.155762] [PMID: 26315829] 
[245] 
Smentek, L. Lanthanides caged by the organic chelates; structural properties. J. Phys. Condens. Matter,  2011, 23(14) 143202
[http://dx.doi.org/10.1088/0953-8984/23/14/143202] [PMID: 21422507] 
[246] 
Chandia, M.; Ketring, A.R.; Cutler, C.S. 177Lu-DOTMP: a new alternative to metastatic bone pain palliation/ formulation studies. J. Labelled Comp. Radiopharm.,  2007, 50(Suppl.), s276.
[247] 
Cutler, C.S.; Bryan, J.N.; Chandia, M.; Irwin, D.J.; Engelbrecht, H.P.; Rold, T.; Lattimer, J.; Hoffman, T.; Henry, C.J.; Ketring, A.R. Evaluation of 177Lu-labeled DOTMP and EDTMP. J. Label Compd. Radiopharm.,  2007, 50(Suppl.), s446.
[248] 
Das, T.; Chakraborty, S.; Unni, P.R.; Banerjee, S.; Samuel, G.; Sarma, H.D.; Venkatesh, M.; Pillai, M.R.A. 177Lu-labeled cyclic polyaminophosphonates as potential agents for bone pain palliation. Appl. Radiat. Isot.,  2002, 57(2), 177-184.
[http://dx.doi.org/10.1016/S0969-8043(02)00104-5] [PMID: 12150276] 
[249] 
Bryan, J.N.; Bommarito, D.; Kim, D.Y.; Berent, L.M.; Bryan, M.E.; Lattimer, J.C.; Henry, C.J.; Engelbrecht, H.; Ketring, A.; Cutler, C. Comparison of systemic toxicities of 177Lu-DOTMP and 153Sm-EDTMP administered intravenously at equivalent skeletal doses to normal dogs. J. Nucl. Med. Technol.,  2009, 37(1), 45-52.
[http://dx.doi.org/10.2967/jnmt.108.054700] [PMID: 19223431] 
[250] 
Hansen, K.; Khanna, C. Spontaneous and genetically engineered animal models; use in preclinical cancer drug development. Eur. J. Cancer,  2004, 40(6), 858-880.
[http://dx.doi.org/10.1016/j.ejca.2003.11.031] [PMID: 15120042] 
[251] 
Das, T.; Shinto, A.; Karuppuswamy Kamaleshwaran, K.; Banerjee, S. Theranostic treatment of metastatic bone pain with 177Lu-DOTMP. Clin. Nucl. Med.,  2016, 41(12), 966-967.
[http://dx.doi.org/10.1097/RLU.0000000000001409] [PMID: 27749428] 
[252] 
Chakraborty, S.; Vimalnath, K.V.; Rajeswari, A.; Chakravarty, R.; Sarma, H.D.; Radhakrishnan, E.; Kamaleshwaran, K.; Shinto, A.S.; Dash, A. A “mix-and-use” approach for formulation of human clinical doses of 177 Lu-DOTMP at hospital radiopharmacy for management of pain arising from skeletal metastases. J. Labelled Comp. Radiopharm.,  2017, 60(9), 410-419.
[http://dx.doi.org/10.1002/jlcr.3517] [PMID: 28477391] 
[253] 
Majkowska, A.; Neves, M.; Antunes, I.; Bilewicz, A. Complexes of low energy beta emitters 47Sc and 177Lu with zoledronic acid for bone pain therapy. Appl. Radiat. Isot.,  2009, 67(1), 11-13.
[http://dx.doi.org/10.1016/j.apradiso.2008.08.014] [PMID: 18929490] 
[254] 
Nikzad, M.; Jalilian, A.R.; Shirvani-Arani, S. Bahrami- Samani, A.; Golchoubian, H. Production, quality control and pharmacokinetic studies of 177Lu-zoledronate for bone pain palliation therapy. J. Radioanal. Nucl. Chem.,  2013, 298, 1273-1281.
[http://dx.doi.org/10.1007/s10967-013-2490-2] 
[255] 
Rasheed, R.; Lodhi, N.D.; Khalid, M.; Mushtaq, M.; Mansoor, M. Radio-synthesis, and in-vivo skeletal localization of 177Lu-zoledronic acid as novel bone seeking therapeutic radiopharmaceutical. J. Anesth. Clin. Res.,  2015, 6(3), 2155-6148.
[http://dx.doi.org/10.4172/2155-6148.1000516] 
[256] 
Zolghadri, S.; Yousefnia, H.; Jalilian, A.R.; Ghannadi-Maragheh, M. Production, biodistribution assessment and dosimetric evaluation of 177Lu-TTHMP as an agent for bone pain palliation. Asia Ocean. J. Nucl. Med. Biol.,  2015, 3(1), 35-42.
[PMID: 27408879] 
[257] 
Bergmann, R.; Meckel, M.; Kubíček, V.; Pietzsch, J.; Steinbach, J.; Hermann, P.; Rösch, F. 177Lu-labelled macrocyclic bisphosphonates for targeting bone metastasis in cancer treatment. EJNMMI Res.,  2016, 6(1), 5.
[http://dx.doi.org/10.1186/s13550-016-0161-3] [PMID: 26780082] 
[258] 
Eisenhut, M. Iodine-131-labeled diphosphonates for the palliative treatment of bone metastases: I. Organ distribution and kinetics of I-131 BDP3 in rats. J. Nucl. Med.,  1984, 25(12), 1356-1361.
[PMID: 6209369] 
[259] 
Eisenhut, M.; Berberich, R.; Kimmig, B.; Oberhausen, E. Iodine-131-labeled diphosphonates for palliative treatment of bone metastases: II. Preliminary clinical results with iodine-131 BDP3. J. Nucl. Med.,  1986, 27(8), 1255-1261.
[PMID: 2426428] 
[260] 
Eisenhut, M.; Fritz, P.; Kimmig, B.; Wingen, F.; Krempien, B. Iodine-131-labeled diphosphonates for the palliative treatment of bone metastases--III. Considerations of interaction, binding and absorbed dose. Int. J. Rad. Appl. Instrum. [A],  1986, 37(8), 741-747.
[http://dx.doi.org/10.1016/0883-2889(86)90269-8] [PMID: 3021676] 
[261] 
Eisenhut, M.; Barber, J.; Taylor, D.M. 131I labeled diphosphonates for the palliative treatment of bone metastases--IV. Syntheses of benzylidenediphosphonates and their organ distribution in rats. Int. J. Rad. Appl. Instrum. A.,  1987, 38(7), 535-540.
[http://dx.doi.org/10.1016/0883-2889(87)90201-2] [PMID: 3040637] 
[262] 
Årstad, E.; Hoff, P.; Skattebøl, L.; Skretting, A.; Breistøl, K. Studies on the synthesis and biological properties of non-carrier-added [125I and 131I]-labeled arylalkylidenebisphosphonates: potent bone-seekers for diagnosis and therapy of malignant osseous lesions. J. Med. Chem.,  2003, 46(14), 3021-3032.
[http://dx.doi.org/10.1021/jm021107v] [PMID: 12825941] 
[263] 
Chakravarty, R.; Dash, A.; Pillai, M.R. Availability of yttrium-90 from strontium-90: a nuclear medicine perspective. Cancer Biother. Radiopharm.,  2012, 27(10), 621-641.
[http://dx.doi.org/10.1089/cbr.2012.1285] [PMID: 23009585] 
[264] 
Keeling, A.A.; Vaughan, A.T.; Beaney, R.P. Yttrium-90-EDTMP: a radiotherapeutic agent in the treatment of leukaemias. Br. J. Cancer,  1989, 60(1), 74-78.
[http://dx.doi.org/10.1038/bjc.1989.223] [PMID: 2803919] 
[265] 
Rajendram, J.G. Therapeutic radioisotope. Nuclear medicine therapy,  2007, 9
[266] 
Kutzner, J.; Dähnert, W.; Schreyer, T.; Grimm, W.; Brod, K.H.; Becker, M. [Treatment of pains from bone metastases with 90Y (author’s transl)]. Nucl. Med. (Stuttg.),  1981, 20(5), 229-235.
[PMID: 6171780] 
[267] 
Ogawa, K.; Kawashima, H.; Shiba, K.; Washiyama, K.; Yoshimoto, M.; Kiyono, Y.; Ueda, M.; Mori, H.; Saji, H. Development of [90Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases. Nucl. Med. Biol.,  2009, 36(2), 129-135.
[http://dx.doi.org/10.1016/j.nucmedbio.2008.11.007] [PMID: 19217524] 
[268] 
Khalid, M.; Bokhari, T.H.; Ahmad, M.; Bhatti, H.N.; Iqbal, M.; Ghaffar, A.; Qadir, M.I. Evaluation of carrier added and no carrier added 90Y-EDTMP as bone seeking therapeutic radiopharmaceutical. Pak. J. Pharm. Sci.,  2014, 27(4), 813-818.
[PMID: 25015445] 
[269] 
Rösch, F.; Herzog, H.; Plag, C.; Neumaier, B.; Braun, U.; Müller-Gärtner, H.W.; Stöcklin, G. Radiation doses of yttrium-90 citrate and yttrium-90 EDTMP as determined via analogous yttrium-86 complexes and positron emission tomography. Eur. J. Nucl. Med.,  1996, 23(8), 958-966.
[http://dx.doi.org/10.1007/BF01084371] [PMID: 8753686] 
[270] 
Mitterhauser, M.; Tögel, S.; Wadsak, W.; Mien, L.K.; Eidherr, H.; Wiesner, K.; Viernstein, H.; Kletter, K.; Dudczak, R. Binding studies of [18F]-fluoride and polyphosphonates radiolabelled with [111In], [99mTc], [153Sm], and [188Re] on bone compartments: a new model for the pre vivo evaluation of bone seekers? Bone,  2004, 34(5), 835-844.
[http://dx.doi.org/10.1016/j.bone.2004.01.011] [PMID: 15121015] 
[271] 
Izotóp. Izotóp Intézet Kft. Available at:. http://www.izotop.hu/pdf/spc/yik26_a.pdf  (Accessed: 27 June, 2018).
[272] 
Byegård, J.; Skarnemark, G.; Skalberg, M. The stability of some metal EDTA, DTPA and DOTA complexes: application as tracers in groundwater studies. J. Radioanal. Nucl. Chem.,  1999, 241, 281-290.
[http://dx.doi.org/10.1007/BF02347463] 
[273] 
Guleria, M.; Das, T.; Kumar, C.; Sharma, R.; Amirdhanayagam, J.; Sarma, H.D.; Dash, A. Effect of number of bifunctional chelating agents on the pharmacokinetics and immunoreactivity of 177Lu-labeled rituximab: a systemic study. Anticancer. Agents Med. Chem.,  2018, 18(1), 146-153.
[http://dx.doi.org/10.2174/1871520617666170725164530] [PMID: 28745238] 
[274] 
Vitha, T.; Kubícek, V.; Hermann, P.; Elst, L.V.; Muller, R.N.; Kolar, Z.I.; Wolterbeek, H.T.; Breeman, W.A.; Lukes, I.; Peters, J.A. Lanthanide(III) complexes of bis(phosphonate) monoamide analogues of DOTA: bone-seeking agents for imaging and therapy. J. Med. Chem.,  2008, 51(3), 677-683.
[http://dx.doi.org/10.1021/jm7012776] [PMID: 18181563] 
[275] 
Breitz, H.B.; Wendt, R.E., III; Stabin, M.S.; Shen, S.; Erwin, W.D.; Rajendran, J.G.; Eary, J.F.; Durack, L.; Delpassand, E.; Martin, W.; Meredith, R.F.; Eary, J.F. 166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy. J. Nucl. Med.,  2006, 47(3), 534-542.
[PMID: 16513624] 
[276] 
Parks, N.J.; Kawakami, T.G.; Avila, M.J.; White, R.; Cain, G.R.; Raaka, S.D.; Hornoff, W.; Fisher, P.; Moore, P.; Seibert, J.A. Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP). Blood,  1993, 82(1), 318-325.
[http://dx.doi.org/10.1182/blood.V82.1.318.bloodjournal821318] [PMID: 8324232] 
[277] 
Bahrami-Samani, A.; Bagheri, R.; Jalilian, A.R.; Shirvani-Arani, S.; Ghannadi-Maragheh, M.; Shamsaee, M. Production, quality control and pharmacokinetic studies of Ho-EDTMP for therapeutic applications. Sci. Pharm.,  2010, 78(3), 423-433.
[http://dx.doi.org/10.3797/scipharm.1004-21] [PMID: 21179355] 
[278] 
Louw, W.K.; Dormehl, I.C.; van Rensburg, A.J.; Hugo, N.; Alberts, A.S.; Forsyth, O.E.; Beverley, G.; Sweetlove, M.A.; Marais, J.; Lötter, M.G.; van Aswegen, A. Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model. Nucl. Med. Biol.,  1996, 23(8), 935-940.
[http://dx.doi.org/10.1016/S0969-8051(96)00117-5] [PMID: 9004281] 
[279] 
Appelbaum, F.R.; Brown, P.A.; Sandmaier, B.M.; Storb, R.; Fisher, D.R.; Shulman, H.M.; Graham, T.C.; Schuening, F.G.; Deeg, H.J.; Bianco, J.A.; Ketring, A.R.; Kaplan, D. Specific marrow ablation before marrow transplantation using an aminophosphonic acid conjugate 166Ho-EDTMP. Blood,  1992, 80(6), 1608-1613.
[http://dx.doi.org/10.1182/blood.V80.6.1608.1608] [PMID: 1520886] 
[280] 
Pedraza-López, M.; Ferro-Flores, G.; Arteaga de Murphy, C.; Morales-Ramírez, P.; Piedras-Ross, J.; Murphy-Stack, E.; Hernández-Oviedo, O. Cytotoxic and genotoxic effect of the [166Dy]Dy/166Ho-EDTMP in vivo generator system in mice. Nucl. Med. Biol.,  2004, 31(8), 1079-1085.
[http://dx.doi.org/10.1016/j.nucmedbio.2004.08.010] [PMID: 15607490] 
[281] 
Pedraza-López, M.; Ferro-Flores, G.; de Murphy, C.A.; Tendilla, J.I.; Villanueva-Sánchez, O. Preparation of 166Dy/166Ho-EDTMP: a potential in vivo generator system for bone marrow ablation. Nucl. Med. Commun.,  2004, 25(6), 615-621.
[http://dx.doi.org/10.1097/01.mnm.0000126516.57329.07] [PMID: 15167523] 
[282] 
Volkert, W.A.; Hoffman, T.J. Therapeutic radiopharmaceuticals. Chem. Rev.,  1999, 99(9), 2269-2292.
[http://dx.doi.org/10.1021/cr9804386] [PMID: 11749482] 
[283] 
Rajendran, J.G.; Eary, J.F.; Bensinger, W.; Durack, L.D.; Vernon, C.; Fritzberg, A. High-dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation. J. Nucl. Med.,  2002, 43(10), 1383-1390.
[PMID: 12368378] 
[284] 
Bayouth, J.E.; Macey, D.J.; Boyer, A.L.; Champlin, R.E. Radiation dose distribution within the bone marrow of patients receiving holmium-166-labeled-phosphonate for marrow ablation. Med. Phys.,  1995, 22(6), 743-753.
[http://dx.doi.org/10.1118/1.597491] [PMID: 7565363] 
[285] 
Bayouth, J.E.; Macey, D.J.; Kasi, L.P.; Garlich, J.R.; McMillan, K.; Dimopoulos, M.A.; Champlin, R.E. Pharmacokinetics, dosimetry and toxicity of holmium-166-DOTMP for bone marrow ablation in multiple myeloma. J. Nucl. Med.,  1995, 36(5), 730-737.
[PMID: 7738641] 
[286] 
Bayouth, J.E.; Macey, D.J. Quantitative imaging of holmium-166 with an Anger camera. Phys. Med. Biol.,  1994, 39(2), 265-279.
[http://dx.doi.org/10.1088/0031-9155/39/2/004] [PMID: 15552124] 
[287] 
Zolghadri, S.; Jalilian, A.R.; Naseri, Z.; Yousefnia, H.; Bahrami-Samani, A.; Ghannadi-Maragheh, M.; Afarideh, H. Production, quality control and biological evaluation of 166Ho-PDTMP as a possible bone palliation agent. Iran. J. Basic Med. Sci.,  2013, 16(5), 719-725.
[PMID: 23826495] 
[288] 
Zolghadri, S.; Jalilian, A.R.; Yousefnia, H. Bahrami- Samani, A.; Ghannadi-Maragheh, M. Development of (166) Holmium-1,2 propylene di-amino tetra (methylenephosphonicacid) as a possible bone palliation agent. World J. Nucl. Med.,  2014, 13(1), 28-33.
[http://dx.doi.org/10.4103/1450-1147.138571] [PMID: 25191109] 
[289] 
Zolghadri, S.; Yousefnia, H.; Jalilian, A.R.; Shiri-Yekta, Z.; Maragheh, M.G. Preliminary dosimetry of 166Ho-propylene di-amino tetra (methy1enephosphonicacid) for human based on biodistribution data in rats. J. Cancer Res. Ther.,  2015, 11(4), 862-867.
[http://dx.doi.org/10.4103/0973-1482.140827] [PMID: 26881532] 
[290] 
Mathew, B.; Chakraborty, S.; Das, T.; Sarma, H.D.; Banerjee, S.; Samuel, G.; Venkatesh, M.; Pillai, M.R.A. 175Yb labeled polyaminophosphonates as potential agents for bone pain palliation. Appl. Radiat. Isot.,  2004, 60(5), 635-642.
[http://dx.doi.org/10.1016/j.apradiso.2003.09.016] [PMID: 15082040] 
[291] 
Mathew, B. Pushparaja; Sarma, H.D.; Chakraborty, S.; Unni, P.R.; Das, T.; Banerjee, S.; Samuel, G.; Venkatesh, M.; Pillai, M.R.A. Dosimetric evaluation of 175Yb-labeled radiopharmaceuticals for the treatment of osseous metastases. Radiat. Prot. Environ.,  2002, 25, 72-76.
[292] 
Fakhari, A.; Jalilian, A.R.; Yousefnia, H.; Shanehsazzadeh, S.; Samani, A.B.; Daha, F.J.; Ardestani, M.S.; Khalaj, A. Preparation, biological evaluation and dosimetry studies of 175Yb-bis-phosphonates for palliative treatment of bone pain. Mol. Imaging Radionucl. Ther.,  2015, 24(3), 110-119.
[http://dx.doi.org/10.4274/mirt.36036] [PMID: 27529886] 
[293] 
Safarzadeh, L. 175Yb-TTHMP as a good candidate for bone pain palliation and substitute of other radiopharmaceuticals. Indian J. Nucl. Med.,  2014, 29(3), 135-139.
[http://dx.doi.org/10.4103/0972-3919.136555] [PMID: 25210277] 
[294] 
Das, T.; Chakraborty, S.; Sarma, H.D.; Tandon, P.; Banerjee, S.; Venkatesh, M.; Pillai, M.R.A. 170Tm-EDTMP: a potential cost-effective alternative to 89SrCl2 for bone pain palliation. Nucl. Med. Biol.,  2009, 36(5), 561-568.
[http://dx.doi.org/10.1016/j.nucmedbio.2009.02.002] [PMID: 19520297] 
[295] 
Shirvani-Arani, S.; Bahrami-Samani, A.; Meftahi, M.; Jalilian, A.R.; Ghannadi-Maragheh, M. Production, quality control and biodistribution studies of thulium-170-labeled ethylenediamine (tetramethylene phosphonic acid). Radiochim. Acta,  2013, 101, 37-44.
[http://dx.doi.org/10.1524/ract.2013.1999] 
[296] 
Vats, K.; Das, T.; Sarma, H.D.; Banerjee, S.; Pillai, M.R.A. Radiolabeling, stability studies, and pharmacokinetic evaluation of thulium-170-labeled acyclic and cyclic polyaminopolyphosphonic acids. Cancer Biother. Radiopharm.,  2013, 28(10), 737-745.
[http://dx.doi.org/10.1089/cbr.2013.1475] [PMID: 23931111] 
[297] 
Das, T.; Shinto, A.; Kamaleshwaran, K.K.; Banerjee, S. Prospective alternative of 89SrCl2 for theranostic treatment of metastatic bone pain. Clin. Nucl. Med.,  2017, 42(3), 235-236.
[http://dx.doi.org/10.1097/RLU.0000000000001530] [PMID: 28072622] 
[298] 
Sahiralamkhan, M.; Chakravarty, R.; Chakraborty, S.; Kamaleshwaran, K.K.; Shinto, A.; Dash, A. Irradiation parameters play a crucial role in the (n,γ) production of 170Tm suitable for clinical use in bone pain palliation. J. Radioanal. Nucl. Chem.,  2016, 307, 1105-1113.
[http://dx.doi.org/10.1007/s10967-015-4323-y] 
[299] 
Das, T.; Banerjee, S. Radiopharmaceuticals for metastatic bone pain palliation: available options in the clinical domain and their comparisons. Clin. Exp. Metastasis,  2017, 34(1), 1-10.
[http://dx.doi.org/10.1007/s10585-016-9831-9] [PMID: 27988895] 
[300] 
Moralles, M.; Pascholati, P.R.; Vanin, V.R.; Helene, O. Decay of 159Gd. Appl. Radiat. Isot.,  1995, 46, 133-138.
[http://dx.doi.org/10.1016/0969-8043(94)00101-5] 
[301] 
Arani, S.S.; Ghasemi, S.; Samani, A.B.; Zafarghandi, M.S. Production, quality control, and bio-distribution studies of 159Gd-EDTMP as a palliative agent for bone pain. Electron. Physician,  2015, 7(1), 977-984.https://dx.doi.org/10.14661%2F2015.977-984
[PMID: 26052408] 
[302] 
Kubícek, V.; Rudovský, J.; Kotek, J.; Hermann, P.; Vander Elst, L.; Muller, R.N.; Kolar, Z.I.; Wolterbeek, H.T.; Peters, J.A.; Lukeš, I. A bisphosphonate monoamide analogue of DOTA: a potential agent for bone targeting. J. Am. Chem. Soc.,  2005, 127(47), 16477-16485.
[http://dx.doi.org/10.1021/ja054905u] [PMID: 16305234] 
[303] 
Chakravarty, R.; Chakraborty, S.; Ram, R.; Nair, K.V.V.; Shinde, S.N.; Sarma, H.D.; Dash, A. Metastatic bone pain palliation: exploring newer avenues using neutron activated 45Ca. Nucl. Med. Biol.,  2016, 43, 140-149.
[http://dx.doi.org/10.1016/j.nucmedbio.2015.10.005] [PMID: 26872438] 
[304] 
Samaratunga, R.C.; Thomas, S.R.; Hinnefeld, J.D.; Von Kuster, L.C.; Hyams, D.M.; Moulton, J.S.; Sperling, M.I.; Maxon, H.R., III A Monte Carlo simulation model for radiation dose to metastatic skeletal tumor from rhenium-186(Sn)-HEDP. J. Nucl. Med.,  1995, 36(2), 336-350.
[PMID: 7830140] 
[305] 
Baczyk, M.; Czepczyński, R.; Milecki, P.; Pisarek, M.; Oleksa, R.; Sowiński, J. 89Sr versus 153Sm-EDTMP: comparison of treatment efficacy of painful bone metastases in prostate and breast carcinoma. Nucl. Med. Commun.,  2007, 28(4), 245-250.
[http://dx.doi.org/10.1097/MNM.0b013e32805b72a0] [PMID: 17325585] 
[306] 
Liepe, K.; Runge, R.; Kotzerke, J. The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain. J. Cancer Res. Clin. Oncol.,  2005, 131(1), 60-66.
[http://dx.doi.org/10.1007/s00432-004-0625-0] [PMID: 15449184] 
[307] 
Liepe, K.; Kotzerke, J. A comparative study of 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr in the treatment of painful skeletal metastases. Nucl. Med. Commun.,  2007, 28(8), 623-630.
[http://dx.doi.org/10.1097/MNM.0b013e32825a6adc] [PMID: 17625384] 
[308] 
Srivastava, S.C. Bone-seeking therapeutic radiopharmaceuticals. Braz. Arch. Biol. Technol.,  2002, 45, 45-55.
[http://dx.doi.org/10.1590/S1516-89132002000500007] 
[309] 
Neves, M.; Kling, A.; Oliveira, A. Radionuclides used for therapy and suggestion for new candidates. J. Radioanal. Nucl. Chem.,  2005, 266, 377-384.
[http://dx.doi.org/10.1007/s10967-005-0920-5] 
[310] 
Unak, P. Targeted tumor radiotherapy. Braz. Arch. Biol. Technol.,  2002, 45, 97-110.
[http://dx.doi.org/10.1590/S1516-89132002000500014] 
[311] 
Sartor, O. Overview of samarium sm 153 lexidronam in the treatment of painful metastatic bone disease. Rev. Urol.,  2004, 6(Suppl. 10), S3-S12.
[PMID: 16985930] 
[312] 
Zalutsky, M.R.; Vaidyanathan, G. Astatine-211-labeled radiotherapeutics: an emerging approach to targeted alpha-particle radiotherapy. Curr. Pharm. Des.,  2000, 6(14), 1433-1455.
[http://dx.doi.org/10.2174/1381612003399275] [PMID: 10903402] 
[313] 
Tavares, A.A.S.; Tavares, J.M.R.S. 99mTc Auger electrons for targeted tumour therapy: a review. Int. J. Radiat. Biol.,  2010, 86(4), 261-270.
[http://dx.doi.org/10.3109/09553000903564083] [PMID: 20353336] 
[314] 
Mertens, W.C.; Stitt, L.; Porter, A.T. Strontium 89 therapy and relief of pain in patients with prostatic carcinoma metastatic to bone: a dose response relationship? Am. J. Clin. Oncol.,  1993, 16(3), 238-242.
[http://dx.doi.org/10.1097/00000421-199306000-00009] [PMID: 7687818] 
[315] 
Buchali, K.; Correns, H.J.; Schuerer, M.; Schnorr, D.; Lips, H.; Sydow, K. Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma. Eur. J. Nucl. Med.,  1988, 14(7-8), 349-351.
[http://dx.doi.org/10.1007/BF00254382] [PMID: 2460352] 
[316] 
Lewington, V.J.; McEwan, A.J.; Ackery, D.M.; Bayly, R.J.; Keeling, D.H.; Macleod, P.M.; Porter, A.T.; Zivanovic, M.A. A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone. Eur. J. Cancer,  1991, 27(8), 954-958.
[http://dx.doi.org/10.1016/0277-5379(91)90257-E] [PMID: 1716935] 
[317] 
Sandeman, T.F.; Budd, R.S.; Martin, J.J. Samarium-153-labelled EDTMP for bone metastases from cancer of the prostate. Clin. Oncol. (R. Coll. Radiol.),  1992, 4(3), 160-164.
[http://dx.doi.org/10.1016/S0936-6555(05)81078-7] [PMID: 1375094] 
[318] 
de Klerk, J.M.H.; Zonnenberg, B.A.; van het Schip, A.D.; van Dijk, A.; Han, S.H.; Quirijnen, J.M.S.R.; Blijham, G.H.; van Rijk, P.P. Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer. Eur. J. Nucl. Med.,  1994, 21(10), 1114-1120.
[http://dx.doi.org/10.1007/BF00181067] [PMID: 7530199] 
[319] 
Pirayesh, E.; Amoui, M.; Mirzaee, H.R.; Tabei, F.; Rakhsha, A.; Kalantari, B.A.; Shafiei, B.; Assadi, M.; Asli, I.N. Phase 2 study of a high dose of 186Re-HEDP for bone pain palliation in patients with widespread skeletal metastases. J. Nucl. Med. Technol.,  2013, 41(3), 192-196.
[http://dx.doi.org/10.2967/jnmt.113.124297] [PMID: 23918612] 
[320] 
Sartor, O.; Reid, R.H.; Bushnell, D.L.; Quick, D.P.; Ell, P.J. Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Cancer,  2007, 109(3), 637-643.
[http://dx.doi.org/10.1002/cncr.22431] [PMID: 17167764] 
[321] 
Porter, A.T.; McEwan, A.J.B.; Powe, J.E.; Reid, R.; McGowan, D.G.; Lukka, H.; Sathyanarayana, J.R.; Yakemchuk, V.N.; Thomas, G.M.; Erlich, L.E.; Crook, J.; Gulenchyn, K.Y.; Hong, K.E.; Wesolowski, C.; Yardley, J. Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer. Int. J. Radiat. Oncol. Biol. Phys.,  1993, 25(5), 805-813.
[http://dx.doi.org/10.1016/0360-3016(93)90309-J] [PMID: 8478230] 
[322] 
Quilty, P.M.; Kirk, D.; Bolger, J.J.; Dearnaley, D.P.; Lewington, V.J.; Mason, M.D.; Reed, N.S.; Russell, J.M.; Yardley, J. A comparison of the palliative effects of strontium-89 and external beam radiotherapy in metastatic prostate cancer. Radiother. Oncol.,  1994, 31(1), 33-40.
[http://dx.doi.org/10.1016/0167-8140(94)90411-1] [PMID: 7518932] 
[323] 
Mertens, W.C.; Porter, A.T.; Reid, R.H.; Powe, J.E. Strontium-89 and low-dose infusion cisplatin for patients with hormone refractory prostate carcinoma metastatic to bone: a preliminary report. J. Nucl. Med.,  1992, 33(8), 1437-1443.
[PMID: 1634933] 
[324] 
Sciuto, R.; Festa, A.; Rea, S.; Pasqualoni, R.; Bergomi, S.; Petrilli, G.; Maini, C.L. Effects of low-dose cisplatin on 89Sr therapy for painful bone metastases from prostate cancer: a randomized clinical trial. J. Nucl. Med.,  2002, 43(1), 79-86.
[PMID: 11801708] 
[325] 
Tu, S.M.; Millikan, R.E.; Mengistu, B.; Delpassand, E.S.; Amato, R.J.; Pagliaro, L.C.; Daliani, D.; Papandreou, C.N.; Smith, T.L.; Kim, J.; Podoloff, D.A.; Logothetis, C.J. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet,  2001, 357(9253), 336-341.
[http://dx.doi.org/10.1016/S0140-6736(00)03639-4] [PMID: 11210994] 
[326] 
Amato, R.J.; Hernandez-McClain, J.; Henary, H. Bone-targeted therapy: phase II study of strontium-89 in combination with alternating weekly chemohormonal therapies for patients with advanced androgen-independent prostate cancer. Am. J. Clin. Oncol.,  2008, 31(6), 532-538.
[http://dx.doi.org/10.1097/COC.0b013e318172aa92] [PMID: 19060583] 
[327] 
Ricci, S.; Boni, G.; Pastina, I.; Genovesi, D.; Cianci, C.; Chiacchio, S.; Orlandini, C.; Grosso, M.; Alsharif, A.; Chioni, A.; Di Donato, S.; Francesca, F.; Selli, C.; Rubello, D.; Mariani, G. Clinical benefit of bone-targeted radiometabolic therapy with 153Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer. Eur. J. Nucl. Med. Mol. Imaging,  2007, 34(7), 1023-1030.
[http://dx.doi.org/10.1007/s00259-006-0343-8] [PMID: 17242920] 
[328] 
Morris, M.J.; Pandit-Taskar, N.; Carrasquillo, J.; Divgi, C.R.; Slovin, S.; Kelly, W.K.; Rathkopf, D.; Gignac, G.A.; Solit, D.; Schwartz, L.; Stephenson, R.D.; Hong, C.; Delacruz, A.; Curley, T.; Heller, G.; Jia, X.; O’Donoghue, J.; Larson, S.; Scher, H.I. Phase I study of samarium-153 lexidronam with docetaxel in castration-resistant metastatic prostate cancer. J. Clin. Oncol.,  2009, 27(15), 2436-2442.
[http://dx.doi.org/10.1200/JCO.2008.20.4164] [PMID: 19364960] 
[329] 
Fizazi, K.; Beuzeboc, P.; Lumbroso, J.; Haddad, V.; Massard, C.; Gross-Goupil, M.; Di Palma, M.; Escudier, B.; Theodore, C.; Loriot, Y.; Tournay, E.; Bouzy, J.; Laplanche, A. Phase II trial of consolidation docetaxel and samarium-153 in patients with bone metastases from castration-resistant prostate cancer. J. Clin. Oncol.,  2009, 27(15), 2429-2435.
[http://dx.doi.org/10.1200/JCO.2008.18.9811] [PMID: 19364971] 
[330] 
van Dodewaard-de Jong, J.M.; de Klerk, J.M.; Bloemendal, H.J.; van Bezooijen, B.P.; de Haas, M.J.; Wilson, R.H.; O’Sullivan, J.M. A phase I study of combined docetaxel and repeated high activity 186Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial). Eur. J. Nucl. Med. Mol. Imaging,  2011, 38(11), 1990-1998.
[http://dx.doi.org/10.1007/s00259-011-1883-0] [PMID: 21792569] 
[331] 
Hoskin, P.; Sartor, O.; O’Sullivan, J.M.; Johannessen, D.C.; Helle, S.I.; Logue, J.; Bottomley, D.; Nilsson, S.; Vogelzang, N.J.; Fang, F.; Wahba, M.; Aksnes, A.K.; Parker, C. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol.,  2014, 15(12), 1397-1406.
[http://dx.doi.org/10.1016/S1470-2045(14)70474-7] [PMID: 25439694] 
[332] 
Morris, M.J.; Hammers, H.J.; Sweeney, C.; Bloma, M.; Aksnes, A.K.; O’Bryan-Tear, C.G.; Carrasquillo, J.A. A phase I/IIa study of the safety and efficacy of radium-223 chloride (Ra-223) with docetaxel (D) for castration-resistant prostate cancer (CRPC) patients with bone metastases. J. Clin. Oncol.,  2013, 30 TPS4694
[http://dx.doi.org/10.1200/jco.2012.30.15_suppl.tps4694] 
[333] 
Pecherstorfer, M.; Schilling, T.; Janisch, S.; Woloszczuk, W.; Baumgartner, G.; Ziegler, R.; Ogris, E. Effect of clodronate treatment on bone scintigraphy in metastatic breast cancer. J. Nucl. Med.,  1993, 34(7), 1039-1044.
[PMID: 8315476] 
[334] 
Carrasquillo, J.A.; Whatley, M.; Dyer, V.; Figg, W.D.; Dahut, W. Alendronate does not interfere with 99mTc-methylene diphosphonate bone scanning. J. Nucl. Med.,  2001, 42(9), 1359-1363.
[PMID: 11535725] 
[335] 
Marcus, C.S.; Saeed, S.; Mlikotic, A.; Mishkin, F.; Pham, H.L.; Javellana, T.; Diestelhorst, S.; Minami, C. Lack of effect of a bisphosphonate (pamidronate disodium) infusion on subsequent skeletal uptake of Sm-153 EDTMP. Clin. Nucl. Med.,  2002, 27(6), 427-430.
[http://dx.doi.org/10.1097/00003072-200206000-00008] [PMID: 12045435] 
[336] 
Leondi, A.; Valotassiou, V.; Leontopoulou, S. Effect of combined biphosphonates and 186Re-HEDP in women with breast cancer and disseminated bone metastases. Turk. J.Nucl. Med.,  2004, 13(1), 69.
[337] 
Liang, J.G.; Jiang, N.Y.; Du, J.Q.; Lu, X.P.; Liu, X.G.; Chen, S.X. [Clinical value of combined therapy with 188Re-HEDP and pamidronate in breast cancer with bone metastasis]. Zhonghua Zhong Liu Za Zhi,  2005, 27(3), 180-182.
[PMID: 15946573] 
[338] 
Storto, G.; Klain, M.; Paone, G.; Liuzzi, R.; Molino, L.; Marinelli, A.; Soricelli, A.; Pace, L.; Salvatore, M. Combined therapy of Sr-89 and zoledronic acid in patients with painful bone metastases. Bone,  2006, 39(1), 35-41.
[http://dx.doi.org/10.1016/j.bone.2005.12.004] [PMID: 16434248] 
[339] 
Wang, R.F.; Zhang, C.L.; Zhu, S.L.; Zhu, M. A comparative study of samarium-153-ethylenediaminetetramethylene phosphonic acid with pamidronate disodium in the treatment of patients with painful metastatic bone cancer. Med. Princ. Pract.,  2003, 12(2), 97-101.
[http://dx.doi.org/10.1159/000069120] [PMID: 12634464] 
[340] 
Lam, M.G.; Dahmane, A.; Stevens, W.H.; van Rijk, P.P.; de Klerk, J.M.; Zonnenberg, B.A. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases. Eur. J. Nucl. Med. Mol. Imaging,  2008, 35(4), 756-765.
[http://dx.doi.org/10.1007/s00259-007-0659-z] [PMID: 18157530] 
[341] 
Soerdjbalie-Maikoe, V.; Pelger, R.C.; Lycklama à Nijeholt, G.A.; Arndt, J.W.; Zwinderman, A.H.; Papapoulos, S.E.; Hamdy, N.A. Strontium-89 (Metastron) and the bisphosphonate olpadronate reduce the incidence of spinal cord compression in patients with hormone-refractory prostate cancer metastatic to the skeleton. Eur. J. Nucl. Med. Mol. Imaging,  2002, 29(4), 494-498.
[http://dx.doi.org/10.1007/s00259-001-0728-7] [PMID: 11914887] 
[342] 
Lam, M.G.; de Klerk, J.M.; Zonnenberg, B.A. Treatment of painful bone metastases in hormone-refractory prostate cancer with zoledronic acid and samarium-153-ethylenediaminetetramethylphosphonic acid combined. J. Palliat. Med.,  2009, 12(7), 649-651.
[http://dx.doi.org/10.1089/jpm.2009.9591] [PMID: 19594354] 
[343] 
O’Sullivan, J.M.; McCready, V.R.; Flux, G.; Norman, A.R.; Buffa, F.M.; Chittenden, S.; Guy, M.; Pomeroy, K.; Cook, G.; Gadd, J.; Treleaven, J.; Al-Deen, A.; Horwich, A.; Huddart, R.A.; Dearnaley, D.P. High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone. Br. J. Cancer,  2002, 86(11), 1715-1720.
[http://dx.doi.org/10.1038/sj.bjc.6600348] [PMID: 12087455] 
[344] 
O’Sullivan, J.M.; Norman, A.R.; McCready, V.R.; Flux, G.; Buffa, F.M.; Johnson, B.; Coffey, J.; Cook, G.; Treleaven, J.; Horwich, A.; Huddart, R.A.; Parker, C.C.; Dearnaley, D.P. A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone. Eur. J. Nucl. Med. Mol. Imaging,  2006, 33(9), 1055-1061.
[http://dx.doi.org/10.1007/s00259-005-0010-5] [PMID: 16572306] 
[345] 
Hernandez, R.; Patel, R.; Grudzinski, J.; Carlson, P.; Sriramaneni, R.; Brown, R.; Bednarz, B.; Sondel, P.; Morris, Z.; Weichert, J. Combination of targeted radionuclide therapy and checkpoint blockade augments therapeutic response in a syngeneic murine model of melanoma. J. Nucl. Med.,  2018, 59(Suppl. 1), 119.
[346] 
Code of Federal Regulations Title 21, Subpart B: Investigational
New Drug Application (IND). 312.20 – Requirement
for an IND. 21 CFR 312.20. Available at:, https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/C FRSearch.cfm?fr=312.20 2014.  (Accessed: 27 June, 2018).
[347] 
Code of Federal Regulations Title 21, Subpart B: Investigational
New Drug Application (IND)., 312.23 - IND content
and format. 21 CFR Sect. 312.23. Available at:. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/C FRSearch.cfm?fr=312.23 2014.  (Accessed: 27 June, 2018).
[348] 
Code of Federal Regulations Title 21, Subpart B: Investigational
New Drug Application (IND)., 312.22 - General principles
of the IND submission, 21 CFR Sect. 312.22. Available
at:. https://www.accessdata.fda.gov/scripts/cdrh/ cfdocs/cfcfr/C FRSearch.cfm?fr=312.22 2014.  (Accessed:
27 June, 2018).
[349] 
Code of Federal Regulations Title 21, Subchapter D: Drugs
for Human Use, (Part 314) - Applications for FDA approval
to market a new drug, 21 CFR Sect. Available at:. https://www.law.cornell.edu/cfr/text/21/part-314 2014.  (Accessed:
27 June, 2018).
[350] 
Guidelines on Current Good Radiopharmacy Practice
(CGRPP) in the preparation of radiopharmaceuticals. cGRPP-guidelines, EANM Radiopharmacy Committee,
Version 2, March. http://www.eanm.org/scientific_info/ guidelines/gl_radioph_ cgrpp.pdf 2007.  (Accessed: 27th
June, 2018).
[351] 
Elsinga, P.; Todde, S.; Penuelas, I.; Meyer, G.; Farstad, B.; Faivre-Chauvet, A.; Mikolajczak, R.; Westera, G.; Gmeiner-Stopar, T.; Decristoforo, C. Radiopharmacy Committee of the EANM. Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur. J. Nucl. Med. Mol. Imaging,  2010, 37(5), 1049-1062.
[http://dx.doi.org/10.1007/s00259-010-1407-3] [PMID: 20306035] 
[352] 
Callahan, R.J. The role of commercial nuclear pharmacy in the future practice of nuclear medicine. Semin. Nucl. Med.,  1996, 26(2), 85-90.
[http://dx.doi.org/10.1016/S0001-2998(96)80029-8] [PMID: 8723502] 
[353] 
Saha, G.B. Fundamentals of Nuclear Pharmacy, 6th ed; , 2010. 
[http://dx.doi.org/10.1007/978-1-4419-5860-0] 
[354] 
Ramírez de Arellano, I.; Piera, C.; Pavia, J.; Setoain, J. Experiences in setting up the first centralized radiopharmacy in Spain. Nucl. Med. Commun.,  1999, 20(3), 279-285.
[http://dx.doi.org/10.1097/00006231-199903000-00012] [PMID: 10093079] 
[355] 
Elliott, A.T.; Hilditch, T.E.; Murray, T.; McNulty, H. The design and construction of a central radiopharmacy. Nucl. Med. Commun.,  1993, 14(4), 328-334.
[http://dx.doi.org/10.1097/00006231-199304000-00174] [PMID: 8479674] 
[356] 
Das, T.; Sarma, H.D.; Shinto, A.; Kamaleshwaran, K.K.; Banerjee, S. Formulation, preclinical evaluation, and preliminary clinical investigation of an in-house freeze-dried EDTMP kit suitable for the preparation of 177Lu-EDTMP. Cancer Biother. Radiopharm.,  2014, 29(10), 412-421.
[http://dx.doi.org/10.1089/cbr.2014.1664] [PMID: 25409337] 
[357] 
Macklis, R.; Lasher, J. Palliative radiotherapy for skeletal metastases: cost-substitution analyses and economic impact. J. Oncol. Manag.,  1999, 8(2), 17-22.
[PMID: 10387551] 
[358] 
Papatheofonis, F.J. Short term reduction in pain medication costs following systemic radionuclide therapy in prostate cancer patients. Veterans Health Syst. J.,  1998, 3, 63-66.
[359] 
Kutzner, J.; Grimm, W.; Hahn, K. Palliative strahlentherapie mit strontium-89 bei ausgedehnter skelettmetastasierung. Strahientherapie,  1978, 154(5), 317-322.
[360] 
Correns, H.J.; Mitterlechner, E.; Buchali, K.; Schnorr, K.D.; Seidel, C.; Mebel, M. [2 years of experience with 89Sr therapy of multiple bone metastases (author’s transl)]. Radiobiol. Radiother. (Berl.),  1979, 20(3), 360-362.
[PMID: 515396] 
[361] 
Hayek, D.; Ritschard, J.; Zwahlen, A.; Courvoisier, B.; Donath, A. [Use of strontium-89 in the analgesic treatment of bone metastases]. Schweiz. Med. Wochenschr.,  1980, 110(31-32), 1154-1159.
[PMID: 7444409] 
[362] 
Kimmig, B.; Hermann, H.J.; Kober, B. [Nuclear medicine therapy of bone metastases]. Rontgenblatter,  1983, 36(7), 216-219.
[PMID: 6622951] 
[363] 
Buchali, K.; Correns, H.J.; Schnorr, D.; Schuerer, M.; Sydow, K.; Lips, H. 89-strontium-therapy of skeletal metastases of prostatic carcinoma. In: Radioactive isotopes in clinic and research; , 1984; pp. 151-156.
[364] 
Fuster, D.; Herranz, R.; Alcover, J.; Mateos, J.J.; Martín, F.; Vidal-Sicart, S.; Pons, F. [Treatment of metastatic bone pain with repeated doses of strontium-89 in patients with prostate neoplasm]. Rev. Esp. Med. Nucl.,  2000, 19(4), 270-274.
[http://dx.doi.org/10.1016/s0212-6982(00)71874-x] [PMID: 11062097] 
[365] 
Kraeber-Bodéré, F.; Campion, L.; Rousseau, C.; Bourdin, S.; Chatal, J.F.; Resche, I. Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement. Eur. J. Nucl. Med.,  2000, 27(10), 1487-1493.
[http://dx.doi.org/10.1007/s002590000315] [PMID: 11083537] 
[366] 
Turner, S.L.; Gruenewald, S.; Spry, N.; Gebski, V. Less pain does equal better quality of life following strontium-89 therapy for metastatic prostate cancer. Br. J. Cancer,  2001, 84(3), 297-302.
[http://dx.doi.org/10.1054/bjoc.2000.1610] [PMID: 11161391] 
[367] 
Ashayeri, E.; Omogbehin, A.; Sridhar, R.; Shankar, R.A. Strontium 89 in the treatment of pain due to diffuse osseous metastases: a university hospital experience. J. Natl. Med. Assoc.,  2002, 94(8), 706-711.
[PMID: 12152927] 
[368] 
Zorga, P.; Birkenfeld, B. Strontium-89 in palliative treatment of painfull bone metastases. Ortop. Traumatol. Rehabil.,  2003, 5(3), 369-373.
[PMID: 18034034] 
[369] 
Baczyk, M.; Milecki, P.; Baczyk, E.; Sowiński, J. The effectiveness of strontium 89 in palliative therapy of painful prostate cancer bone metastases. Ortop. Traumatol. Rehabil.,  2003, 5(3), 364-368.
[PMID: 18034033] 
[370] 
Gunawardana, D.H.; Lichtenstein, M.; Better, N.; Rosenthal, M. Results of strontium-89 therapy in patients with prostate cancer resistant to chemotherapy. Clin. Nucl. Med.,  2004, 29(2), 81-85.
[http://dx.doi.org/10.1097/01.rlu.0000109721.58471.44] [PMID: 14734902] 
[371] 
Ma, Y.B.; Yan, W.L.; Dai, J.C.; Xu, F.; Yuan, Q.; Shi, H.H. Strontium-89: a desirable therapeutic for bone metastases of prostate cancer. Zhonghua. Nan. Ke. Xue.,  2008, 14(9), 819-822.
[PMID: 18998467] 
[372] 
Serafini, A.N. Current status of systemic intravenous radiopharmaceuticals for the treatment of painful metastatic bone disease. Int. J. Radiat. Oncol. Biol. Phys.,  1994, 30(5), 1187-1194.
[http://dx.doi.org/10.1016/0360-3016(94)90327-1] [PMID: 7525518] 
[373] 
Tian, J.H.; Zhang, J.M.; Hou, Q.T.; Oyang, Q.H.; Wang, J.M.; Luan, Z.S.; Chuan, L.; He, Y.J. Multicentre trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China. Eur. J. Nucl. Med.,  1999, 26(1), 2-7.
[http://dx.doi.org/10.1007/s002590050351] [PMID: 9933654] 
[374] 
Dolezal, J. Systemic radionuclide therapy with Samarium-153-EDTMP for painful bone metastases. Nucl. Med. Rev. Cent. East. Eur.,  2000, 3(2), 161-163.
[PMID: 14600912] 
[375] 
Sapienza, M.T.; Ono, C.R.; Guimarães, M.I.C.; Watanabe, T.; Costa, P.A.; Buchpiguel, C.A. Retrospective evaluation of bone pain palliation after samarium-153-EDTMP therapy. Rev. Hosp. Clin. Fac. Med. S. Paulo,  2004, 59(6), 321-328.
[http://dx.doi.org/10.1590/S0041-87812004000600003] [PMID: 15654484] 
[376] 
Etchebehere, E.C.S.D.C.; Neto, C.A.C.P.; de Lima, M.C.L.; Santos, A.D.O.; Ramos, C.D.; Silva, M.C.; Camargo, E.E. Treatment of bone pain secondary to metastases using samarium-153-EDTMP. Sao Paulo Med. J.,  2004, 122(5), 208-212.
[http://dx.doi.org/10.1590/s1516-31802004000500006] [PMID: 15558143] 
[377] 
Tripathi, M.; Singhal, T.; Chandrasekhar, N.; Kumar, P.; Bal, C.; Jhulka, P.K.; Bandopadhyaya, G.; Malhotra, A. Samarium-153 ethylenediamine tetramethylene phosphonate therapy for bone pain palliation in skeletal metastases. Indian J. Cancer,  2006, 43(2), 86-92.
[http://dx.doi.org/10.4103/0019-509x.25890] [PMID: 16790946] 
[378] 
Ripamonti, C.; Fagnoni, E.; Campa, T.; Seregni, E.; Maccauro, M.; Bombardieri, E. Incident pain and analgesic consumption decrease after samarium infusion: a pilot study. Support. Care Cancer,  2007, 15(3), 339-342.
[http://dx.doi.org/10.1007/s00520-006-0131-9] [PMID: 16967302] 
[379] 
Dolezal, J.; Vizda, J.; Odrazka, K. Prospective evaluation of samarium-153-EDTMP radionuclide treatment for bone metastases in patients with hormone-refractory prostate cancer. Urol. Int.,  2007, 78(1), 50-57.
[http://dx.doi.org/10.1159/000096935] [PMID: 17192733] 
Rights & Permissions Print Cite
Article Metrics
86
3
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0929867326666190201142814	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
当代药物化学

放射性核素靶向治疗疼痛性骨转移:过去的发展，现状，最近的进展和未来的方向

摘要

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

当代药物化学

放射性核素靶向治疗疼痛性骨转移:过去的发展，现状，最近的进展和未来的方向

摘要

Call for Papers in Thematic Issues

Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.

Approaches to the Treatment of Chronic Inflammation

Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications

Chalcogen-modified nucleic acid analogues

Related Journals

Related Books

Related Articles
