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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Insight into Tumor Hypoxia: Radionuclide-based Biomarker as Diagnostic Tools

Author(s): Priya Saxena, Sanjay Gambhir and Manish Dixit*

Volume 23, Issue 12, 2023

Published on: 22 May, 2023

Page: [1136 - 1154] Pages: 19

DOI: 10.2174/1568026623666230515154442

Price: $65

Abstract

The radiolabeled tracers have been extensively utilized to access various physiological and pathological conditions non-invasively, such as cancers, inflammation, and organ-specific imaging. These tracers demonstrate and study tumor hypoxia in several malignancies. Hypoxia is commonly seen in solid tumors. Tumor Hypoxia is a non-physiological condition of reduced oxygen concentration in the tumor. Hypoxia is associated with adverse outcomes such as treatment resistance and metastases in solid tumors. Tumor hypoxia may result in resistance to radiation therapy and chemotherapy, leading to a poor prognosis. It is one of the clinically paramount factors in treatment planning. Various chemical scaffolds are labeled with compatible radioisotopes for imaging hypoxia by Single-photon emission computed tomography (SPECT) and Positron emission tomography (PET). Radionuclides, such as [18F]Flourine, [99mTc]Technetium, [131I]Iodine, [124I] Iodine, and [64Cu]Copper are used for incorporation into different chemical scaffolds.Among them, [18F]Flourine and [64Cu]Copper tagged radiopharmaceuticals are most explored, such as [18F]FMISO, [18F]FAZA, [18F]FETNIM, and N4-methyl thiosemicarbazone [64Cu][Cu (ATSM)]. Some of the promising scaffolds for imaging hypoxia are [18F]EF1, [18F]EF5, [18F]EF3, and [18F]HX4.

This review is focused on developing radiochemistry routes to synthesize different radiopharmaceuticals for imaging hypoxia in clinical and preclinical studies, as described in the literature. The chemist and radiochemist exerted enormous efforts to overcome these obstacles. They have successfully formulated multiple radiopharmaceuticals for hypoxia imaging. Radionuclide incorporation in high selectivity and efficiency (radiochemical yield, specific activity, purity, and radio-scalability) is a need for application perspective. Versatile chemistry, including nucleophilic and electrophilic substitutions, allows the direct or indirect introduction of radioisotopes into molecules of interest. This review will discuss the chemical routes for synthesizing and utilizing different precursors for radiolabeling with radionuclides.We will briefly summaries these radio-labeled tracers' application and biological significance.

Keywords: Radionuclide, Nitroimidazole, Radiotracer, Hypoxia, Diagnostics, Imaging.

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[1]
Alimoradi, H.; Matikonda, S.S.; Gamble, A.B.; Giles, G.I.; Greish, K. Hypoxia responsive drug delivery systems in tumor therapy. Curr. Pharm. Des., 2016, 22(19), 2808-2820.
[http://dx.doi.org/10.2174/1381612822666160217130049] [PMID: 26898739]
[2]
Yeh, J.J.; Kim, W.Y. Targeting tumor hypoxia with hypoxia-activated prodrugs. J. Clin. Oncol., 2015, 33(13), 1505-1508.
[http://dx.doi.org/10.1200/JCO.2014.60.0759] [PMID: 25800764]
[3]
Vaupel, P. Hypoxia and aggressive tumor phenotype: Implications for therapy and prognosis. Oncologist, 2008, 13(S3), 21-26.
[http://dx.doi.org/10.1634/theoncologist.13-S3-21] [PMID: 18458121]
[4]
Vaupel, P.; Höckel, M.; Mayer, A. Detection and characterization of tumor hypoxia using pO2 histography. Antioxid. Redox Signal., 2007, 9(8), 1221-1236.
[http://dx.doi.org/10.1089/ars.2007.1628] [PMID: 17536958]
[5]
Challapalli, A.; Carroll, L.; Aboagye, E.O. Molecular mechanisms of hypoxia in cancer. Clin. Transl. Imaging, 2017, 5(3), 225-253.
[http://dx.doi.org/10.1007/s40336-017-0231-1] [PMID: 28596947]
[6]
Moulder, J.E.; Rockwell, S. Tumor hypoxia: Its impact on cancer therapy. Cancer Metastasis Rev., 1987, 5(4), 313-341.
[http://dx.doi.org/10.1007/BF00055376] [PMID: 3552280]
[7]
Vaupel, P.; Harrison, L. Tumor hypoxia: Causative factors, compensatory mechanisms, and cellular response. Oncologist, 2004, 9(S5)(Suppl. 5), 4-9.
[http://dx.doi.org/10.1634/theoncologist.9-90005-4] [PMID: 15591417]
[8]
Vaupel, P.; Mayer, A. Hypoxia in tumors: Pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications. Adv. Exp. Med. Biol., 2014, 812, 19-24.
[http://dx.doi.org/10.1007/978-1-4939-0620-8_3] [PMID: 24729210]
[9]
Walsh, J.C.; Lebedev, A.; Aten, E.; Madsen, K.; Marciano, L.; Kolb, H.C. The clinical importance of assessing tumor hypoxia: Relationship of tumor hypoxia to prognosis and therapeutic opportunities. Antioxid. Redox Signal., 2014, 21(10), 1516-1554.
[http://dx.doi.org/10.1089/ars.2013.5378] [PMID: 24512032]
[10]
Krohn, K.A.; Link, J.M.; Mason, R.P. Molecular imaging of hypoxia. J. Nucl. Med., 2008, 49(Suppl. 2), 129S-148S.
[http://dx.doi.org/10.2967/jnumed.107.045914] [PMID: 18523070]
[11]
Rademakers, S.E.; Span, P.N.; Kaanders, J.H.A.M.; Sweep, F.C.G.J.; van der Kogel, A.J.; Bussink, J. Molecular aspects of tumour hypoxia. Mol. Oncol., 2008, 2(1), 41-53.
[http://dx.doi.org/10.1016/j.molonc.2008.03.006] [PMID: 19383328]
[12]
Li, Z.; Chu, T. Recent advances on radionuclide labeled hypoxia-imaging agents. Curr. Pharm. Des., 2012, 18(8), 1084-1097.
[http://dx.doi.org/10.2174/138161212799315849] [PMID: 22272826]
[13]
Mottram, J.C. A factor of importance in the radio sensitivity of tumors. Br. J. Radiol., 1936, 9(105), 606-614.
[http://dx.doi.org/10.1259/0007-1285-9-105-606]
[14]
Gray, L.H.; Conger, A.D.; Ebert, M.; Hornsey, S.; Scott, O.C.A. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br. J. Radiol., 1953, 26(312), 638-648.
[http://dx.doi.org/10.1259/0007-1285-26-312-638] [PMID: 13106296]
[15]
Vaupel, P.; Thews, O.; Hoeckel, M. Treatment resistance of solid tumors: Role of hypoxia and anemia. Med. Oncol., 2001, 18(4), 243-260.
[http://dx.doi.org/10.1385/MO:18:4:243] [PMID: 11918451]
[16]
Bertout, J.A.; Patel, S.A.; Simon, M.C. The impact of O2 availability on human cancer. Nat. Rev. Cancer, 2008, 8(12), 967-975.
[http://dx.doi.org/10.1038/nrc2540] [PMID: 18987634]
[17]
Brown, J.M. Clinical trials of radiosensitizers: What should we expect? Int. J. Radiat. Oncol. Biol. Phys., 1984, 10(3), 425-429.
[http://dx.doi.org/10.1016/0360-3016(84)90063-4] [PMID: 6231272]
[18]
Brown, J.M.; Wilson, W.R. Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer, 2004, 4(6), 437-447.
[http://dx.doi.org/10.1038/nrc1367] [PMID: 15170446]
[19]
Spiegelberg, L.; Houben, R.; Niemans, R.; de Ruysscher, D.; Yaromina, A.; Theys, J.; Guise, C.P.; Smaill, J.B.; Patterson, A.V.; Lambin, P.; Dubois, L.J. Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials. Clin. Transl. Radiat. Oncol., 2019, 15, 62-69.
[http://dx.doi.org/10.1016/j.ctro.2019.01.005] [PMID: 30734002]
[20]
Huang, Y.; Fan, J.; Li, Y.; Fu, S.; Chen, Y.; Wu, J. Imaging of Tumor Hypoxia With Radionuclide-Labeled Tracers for PET. Front. Oncol., 2021, 11, 731503.
[http://dx.doi.org/10.3389/fonc.2021.731503]
[21]
Sherwood, L.M.; Parris, E.E.; Folkman, J. Tumor angiogenesis: Therapeutic implications. N. Engl. J. Med., 1971, 285(21), 1182-1186.
[http://dx.doi.org/10.1056/NEJM197111182852108] [PMID: 4938153]
[22]
Semenza, G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer, 2003, 3(10), 721-732.
[http://dx.doi.org/10.1038/nrc1187] [PMID: 13130303]
[23]
Sosa, V.; Moliné, T.; Somoza, R.; Paciucci, R.; Kondoh, H. LLeonart, M.E. Oxidative stress and cancer: An overview. Ageing Res. Rev., 2013, 12(1), 376-390.
[http://dx.doi.org/10.1016/j.arr.2012.10.004] [PMID: 23123177]
[24]
Wilson, W.R.; Hay, M.P. Targeting hypoxia in cancer therapy. Nat. Rev. Cancer, 2011, 11(6), 393-410.
[http://dx.doi.org/10.1038/nrc3064] [PMID: 21606941]
[25]
Nelson, A.R.; Fingleton, B.; Rothenberg, M.L.; Matrisian, L.M. Matrix metalloproteinases: Biologic activity and clinical implications. J. Clin. Oncol., 2000, 18(5), 1135-1149.
[http://dx.doi.org/10.1200/JCO.2000.18.5.1135] [PMID: 10694567]
[26]
Leung, D.W.; Cachianes, G.; Kuang, W.J.; Goeddel, D.V.; Ferrara, N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science, 1989, 246(4935), 1306-1309.
[http://dx.doi.org/10.1126/science.2479986] [PMID: 2479986]
[27]
Nishida, N.; Yano, H.; Nishida, T.; Kamura, T.; Kojiro, M. Angiogenesis in cancer. Vasc. Health Risk Manag., 2006, 2(3), 213-219.
[http://dx.doi.org/10.2147/vhrm.2006.2.3.213] [PMID: 17326328]
[28]
Salven, P.; Lymboussaki, A.; Heikkilä, P.; Jääskela-Saari, H.; Enholm, B.; Aase, K.; von Euler, G.; Eriksson, U.; Alitalo, K.; Joensuu, H. Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. Am. J. Pathol., 1998, 153(1), 103-108.
[http://dx.doi.org/10.1016/S0002-9440(10)65550-2] [PMID: 9665470]
[29]
Gacche, R.N. Compensatory angiogenesis and tumor refractoriness. Oncogenesis, 2015, 4(6), e153.
[http://dx.doi.org/10.1038/oncsis.2015.14] [PMID: 26029827]
[30]
Dewhirst, M.W.; Kimura, H.; Rehmus, S.W.; Braun, R.D.; Papahadjopoulos, D.; Hong, K.; Secomb, T.W. Microvascular studies on the origins of perfusion-limited hypoxia. Br. J. Cancer Suppl., 1996, 27(Suppl. 27), S247-S251.
[PMID: 8763890]
[31]
Jordan, B.F.; Sonveaux, P. Targeting tumor perfusion and oxygenation to improve the outcome of anticancer therapy. Front. Pharmacol., 2012, 3(94), 94.
[PMID: 22661950]
[32]
Wigerup, C.; Påhlman, S.; Bexell, D. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacol. Ther., 2016, 164, 152-169.
[http://dx.doi.org/10.1016/j.pharmthera.2016.04.009] [PMID: 27139518]
[33]
Brown, J.M. Tumor hypoxia in cancer therapy. Methods Enzymol., 2007, 435, 295-321.
[http://dx.doi.org/10.1016/S0076-6879(07)35015-5] [PMID: 17998060]
[34]
Shannon, A.M.; Bouchier-Hayes, D.J.; Condron, C.M.; Toomey, D. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat. Rev., 2003, 29(4), 297-307.
[http://dx.doi.org/10.1016/S0305-7372(03)00003-3] [PMID: 12927570]
[35]
Roberts, D.L.; Williams, K.J.; Cowen, R.L.; Barathova, M.; Eustace, A.J.; Brittain-Dissont, S.; Tilby, M.J.; Pearson, D.G.; Ottley, C.J.; Stratford, I.J.; Dive, C. Contribution of HIF-1 and drug penetrance to oxaliplatin resistance in hypoxic colorectal cancer cells. Br. J. Cancer, 2009, 101(8), 1290-1297.
[http://dx.doi.org/10.1038/sj.bjc.6605311] [PMID: 19755992]
[36]
Durand, R.E. The influence of microenvironmental factors during cancer therapy. In Vivo, 1994, 8(5), 691-702.
[PMID: 7727714]
[37]
Batchelder, R.M.; Wilson, W.R.; Hay, M.P.; Denny, W.A. Oxygen dependence of the cytotoxicity of the enediyne anti-tumour antibiotic esperamicin A1. Br. J. Cancer Suppl., 1996, 27(Suppl. 27), S52-S56.
[PMID: 8763846]
[38]
Sun, X.; Niu, G.; Chan, N.; Shen, B.; Chen, X. Tumor hypoxia imaging. Mol. Imaging Biol., 2011, 13(3), 399-410.
[http://dx.doi.org/10.1007/s11307-010-0420-z] [PMID: 20838906]
[39]
Brizel, D.M.; Sibley, G.S.; Prosnitz, L.R.; Scher, R.L.; Dewhirst, M.W. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int. J. Radiat. Oncol. Biol. Phys., 1997, 38(2), 285-289.
[http://dx.doi.org/10.1016/S0360-3016(97)00101-6] [PMID: 9226314]
[40]
Höckel, M.; Vorndran, B.; Schlenger, K.; Baußmann, E.; Knapstein, P.G. Tumor oxygenation: A new predictive parameter in locally advanced cancer of the uterine cervix. Gynecol. Oncol., 1993, 51(2), 141-149.
[http://dx.doi.org/10.1006/gyno.1993.1262] [PMID: 8276286]
[41]
Powell, M.E.B.; Collingridge, D.R.; Saunders, M.I.; Hoskin, P.J.; Hill, S.A.; Chaplin, D.J. Improvement in human tumour oxygenation with carbogen of varying carbon dioxide concentrations. Radiother. Oncol., 1999, 50(2), 167-171.
[http://dx.doi.org/10.1016/S0167-8140(98)00123-6] [PMID: 10368040]
[42]
Gatenby, R.A.; Moldofsky, P.J.; Weiner, L.M. Metastatic colon cancer: Correlation of oxygen levels with I-131 F(ab’)2 uptake. Radiology, 1988, 166(3), 757-759.
[http://dx.doi.org/10.1148/radiology.166.3.3340773] [PMID: 3340773]
[43]
Pauwels, E.K.J.; Mariani, G. Assessment of tumor tissue oxygenation: Agents, methods and clinical significance. Drug News Perspect., 2007, 20(10), 619-626.
[http://dx.doi.org/10.1358/dnp.2007.20.10.1181355] [PMID: 18301796]
[44]
Rumsey, W.L.; Vanderkooi, J.M.; Wilson, D.F. Imaging of phosphorescence: A novel method for measuring oxygen distribution in perfused tissue. Science, 1988, 241(4873), 1649-1651.
[http://dx.doi.org/10.1126/science.3420417] [PMID: 3420417]
[45]
Lebedev, A.Y.; Cheprakov, A.V. Sakadžić S.; Boas, D.A.; Wilson, D.F.; Vinogradov, S.A. Dendritic phosphorescent probes for oxygen imaging in biological systems. ACS Appl. Mater. Interfaces, 2009, 1(6), 1292-1304.
[http://dx.doi.org/10.1021/am9001698] [PMID: 20072726]
[46]
Ljungkvist, A.S.E.; Bussink, J.; Kaanders, J.H.A.M.; van der Kogel, A.J. Dynamics of tumor hypoxia measured with bioreductive hypoxic cell markers. Radiat. Res., 2007, 167(2), 127-145.
[http://dx.doi.org/10.1667/RR0719.1] [PMID: 17390721]
[47]
Chapman, J.D. Hypoxic sensitizers--implications for radiation therapy. N. Engl. J. Med., 1979, 301(26), 1429-1432.
[http://dx.doi.org/10.1056/NEJM197912273012606] [PMID: 229413]
[48]
Raleigh, J.A.; Calkins-Adams, D.P.; Rinker, L.H.; Ballenger, C.A.; Weissler, M.C.; Fowler, W.C., Jr; Novotny, D.B.; Varia, M.A. Hypoxia and vascular endothelial growth factor expression in human squamous cell carcinomas using pimonidazole as a hypoxia marker. Cancer Res., 1998, 58(17), 3765-3768.
[PMID: 9731480]
[49]
Evans, S.M.; Hahn, S.; Pook, D.R.; Jenkins, W.T.; Chalian, A.A.; Zhang, P.; Stevens, C.; Weber, R.; Weinstein, G.; Benjamin, I.; Mirza, N.; Morgan, M.; Rubin, S.; McKenna, W.G.; Lord, E.M.; Koch, C.J. Detection of hypoxia in human squamous cell carcinoma by EF5 binding. Cancer Res., 2000, 60(7), 2018-2024.
[PMID: 10766193]
[50]
Evans, S.M.; Koch, C.J. Prognostic significance of tumor oxygenation in humans. Cancer Lett., 2003, 195(1), 1-16.
[http://dx.doi.org/10.1016/S0304-3835(03)00012-0] [PMID: 12767506]
[51]
Raleigh, J.A.; Chou, S-C.; Arteel, G.E.; Horsman, M.R. Comparisons among pimonidazole binding, oxygen electrode measurements, and radiation response in C3H mouse tumors. Radiat. Res., 1999, 151(5), 580-589.
[http://dx.doi.org/10.2307/3580034] [PMID: 10319731]
[52]
Toma-Daşu, I.; Daşuu, A.; Brahmeu, A. Quantifying tumour hypoxia by PET imaging--a theoretical analysis. Adv. Exp. Med. Biol., 2009, 645, 267-272.
[http://dx.doi.org/10.1007/978-0-387-85998-9_40] [PMID: 19227481]
[53]
Padhani, A. Science to practice: what does MR oxygenation imaging tell us about human breast cancer hypoxia? Radiology, 2010, 254(1), 1-3.
[http://dx.doi.org/10.1148/radiol.091669] [PMID: 20032129]
[54]
Howe, F.A.; Robinson, S.P.; McIntyre, D.J.O.; Stubbs, M.; Griffiths, J.R. Issues in flow and oxygenation dependent contrast (FLOOD) imaging of tumours. NMR Biomed., 2001, 14(7-8), 497-506.
[http://dx.doi.org/10.1002/nbm.716] [PMID: 11746943]
[55]
Stubbs, M. Application of magnetic resonance techniques for imaging tumour physiology. Acta Oncol., 1999, 38(7), 845-853.
[http://dx.doi.org/10.1080/028418699432536] [PMID: 10606414]
[56]
Tumkur, S.M.; Vu, A.T.; Li, L.P.; Pierchala, L.; Prasad, P.V. Evaluation of intra-renal oxygenation during water diuresis: A time-resolved study using BOLD MRI. Kidney Int., 2006, 70(1), 139-143.
[http://dx.doi.org/10.1038/sj.ki.5000347] [PMID: 16572109]
[57]
O’Connor, J.P.B.; Naish, J.H.; Parker, G.J.M.; Waterton, J.C.; Watson, Y.; Jayson, G.C.; Buonaccorsi, G.A.; Cheung, S.; Buckley, D.L.; McGrath, D.M.; West, C.M.L.; Davidson, S.E.; Roberts, C.; Mills, S.J.; Mitchell, C.L.; Hope, L.; Ton, N.C.; Jackson, A. Preliminary study of oxygen-enhanced longitudinal relaxation in MRI: A potential novel biomarker of oxygenation changes in solid tumors. Int. J. Radiat. Oncol. Biol. Phys., 2009, 75(4), 1209-1215.
[http://dx.doi.org/10.1016/j.ijrobp.2008.12.040] [PMID: 19327904]
[58]
Mason, R.P. Non-invasive assessment of kidney oxygenation: A role for BOLD MRI. Kidney Int., 2006, 70(1), 10-11.
[http://dx.doi.org/10.1038/sj.ki.5001560] [PMID: 16810286]
[59]
Zhao, D.; Ran, S.; Constantinescu, A.; Hahn, E.W.; Mason, R.P. Tumor oxygen dynamics: Correlation of in vivo MRI with histological findings. Neoplasia, 2003, 5(4), 308-318.
[http://dx.doi.org/10.1016/S1476-5586(03)80024-6] [PMID: 14511402]
[60]
van der Sanden, B.P.; Heerschap, A.; Simonetti, A.W.; Rijken, P.F.; Peters, H.P.; Stüben, G.; van der Kogel, A.J. Characterization and validation of noninvasive oxygen tension measurements in human glioma xenografts by 19F-MR relaxometry. Int. J. Radiat. Oncol. Biol. Phys., 1999, 44(3), 649-658.
[http://dx.doi.org/10.1016/S0360-3016(98)00555-0] [PMID: 10348296]
[61]
McNab, J.A.; Yung, A.C.; Kozlowski, P. Tissue oxygen tension measurements in the Shionogi model of prostate cancer using 19F MRS and MRI. MAGMA, 2004, 17(3-6), 288-295.
[http://dx.doi.org/10.1007/s10334-004-0083-3] [PMID: 15605277]
[62]
Davda, S.; Bezabeh, T. Advances in methods for assessing tumor hypoxia in vivo: Implications for treatment planning. Cancer Metastasis Rev., 2006, 25(3), 469-480.
[http://dx.doi.org/10.1007/s10555-006-9009-z] [PMID: 17029029]
[63]
Yu, J.; Kodibagkar, V.; Cui, W.; Mason, R. 19F: A versatile reporter for non-invasive physiology and pharmacology using magnetic resonance. Curr. Med. Chem., 2005, 12(7), 819-848.
[http://dx.doi.org/10.2174/0929867053507342] [PMID: 15853714]
[64]
Hunjan, S.; Zhao, D.; Constantinescu, A.; Hahn, E.W.; Antich, P.P.; Mason, R.P. Tumor oximetry: Demonstration of an enhanced dynamic mapping procedure using fluorine-19 echo planar magnetic resonance imaging in the Dunning prostate R3327-AT1 rat tumor. Int. J. Radiat. Oncol. Biol. Phys., 2001, 49(4), 1097-1108.
[http://dx.doi.org/10.1016/S0360-3016(00)01460-7] [PMID: 11240252]
[65]
Kwock, L.; Gill, M.; McMurry, H.L.; Beckman, W.; Raleigh, J.A.; Joseph, A.P. Evaluation of a fluorinated 2-nitroimidazole binding to hypoxic cells in tumor-bearing rats by 19F magnetic resonance spectroscopy and immunohistochemistry. Radiat. Res., 1992, 129(1), 71-78.
[http://dx.doi.org/10.2307/3577905] [PMID: 1728059]
[66]
Salmon, H.W.; Siemann, D.W. Utility of 19F MRS detection of the hypoxic cell marker EF5 to assess cellular hypoxia in solid tumors. Radiother. Oncol., 2004, 73(3), 359-366.
[http://dx.doi.org/10.1016/j.radonc.2004.07.018] [PMID: 15588883]
[67]
Lee, C.P.; Payne, G.S.; Oregioni, A.; Ruddle, R.; Tan, S.; Raynaud, F.I.; Eaton, D.; Campbell, M.J.; Cross, K.; Halbert, G.; Tracy, M.; McNamara, J.; Seddon, B.; Leach, M.O.; Workman, P.; Judson, I. A phase I study of the nitroimidazole hypoxia marker SR4554 using 19F magnetic resonance spectroscopy. Br. J. Cancer, 2009, 101(11), 1860-1868.
[http://dx.doi.org/10.1038/sj.bjc.6605425] [PMID: 19935799]
[68]
Mees, G.; Dierckx, R.; Vangestel, C.; Van de Wiele, C. Molecular imaging of hypoxia with radiolabelled agents. Eur. J. Nucl. Med. Mol. Imaging, 2009, 36(10), 1674-1686.
[http://dx.doi.org/10.1007/s00259-009-1195-9] [PMID: 19565239]
[69]
Sharma, R. Nitroimidazole radiopharmaceuticals in bioimaging: Part I: Synthesis and imaging applications. Curr. Radiopharm., 2011, 4(4), 361-378.
[http://dx.doi.org/10.2174/1874471011104040361] [PMID: 22202159]
[70]
Ruan, Q.; Zhang, X.; Lin, X.; Duan, X.; Zhang, J. Novel 99mTc labelled complexes with 2-nitroimidazole isocyanide: Design, synthesis and evaluation as potential tumor hypoxia imaging agents. Medchemcomm, 2018, 9(6), 988-994.
[71]
Wang, F.; Yang, X.; Zhu, H.; Yang, Z.; Chu, T. Synthesis and bioevaluation of novel radioiodinated PEG-modified 2-nitroimidazole derivatives for tumor hypoxia imaging. J. Radioanal. Nucl. Chem., 2019, 321(3), 943-954.
[http://dx.doi.org/10.1007/s10967-019-06649-9]
[72]
Goel, S.; Shi, S. Promise of hypoxia-targeted tracers in metastatic lymph node imaging. Eur. J. Nucl. Med. Mol. Imaging, 2022, 49(13), 4293-4297.
[http://dx.doi.org/10.1007/s00259-022-05938-y] [PMID: 35994060]
[73]
Nie, X.; Elvington, A.; Laforest, R.; Zheng, J.; Voller, T.F.; Zayed, M.A.; Abendschein, D.R.; Bandara, N.; Xu, J.; Li, R.; Randolph, G.J.; Gropler, R.J.; Lapi, S.E.; Woodard, P.K. 64 Cu-ATSM Positron Emission Tomography/Magnetic Resonance Imaging of Hypoxia in Human Atherosclerosis. Circ. Cardiovasc. Imaging, 2020, 13(1), e009791.
[http://dx.doi.org/10.1161/CIRCIMAGING.119.009791] [PMID: 31910670]
[74]
Floberg, J.M.; Wang, L.; Bandara, N.; Rashmi, R.; Mpoy, C.; Garbow, J.R.; Rogers, B.E.; Patti, G.J.; Schwarz, J.K. Alteration of cellular reduction potential will change 64 Cu-ATSM signal with or without hypoxia. J. Nucl. Med., 2020, 61(3), 427-432.
[http://dx.doi.org/10.2967/jnumed.119.230805] [PMID: 31586008]
[75]
Rasey, J.S.; Koh, W.; Evans, M.L.; Peterson, L.M.; Lewellen, T.K.; Graham, M.M.; Krohn, K.A. Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: A pretherapy study of 37 patients. Int. J. Radiat. Oncol. Biol. Phys., 1996, 36(2), 417-428.
[http://dx.doi.org/10.1016/S0360-3016(96)00325-2] [PMID: 8892467]
[76]
Souvatzoglou, M.; Grosu, A.L.; Röper, B.; Krause, B.J.; Beck, R.; Reischl, G.; Picchio, M.; Machulla, H.J.; Wester, H.J.; Piert, M. Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: A pilot study. Eur. J. Nucl. Med. Mol. Imaging, 2007, 34(10), 1566-1575.
[http://dx.doi.org/10.1007/s00259-007-0424-3] [PMID: 17447061]
[77]
Kizaka-Kondoh, S.; Konse-Nagasawa, H. Significance of nitroimidazole compounds and hypoxia-inducible factor-1 for imaging tumor hypoxia. Cancer Sci., 2009, 100(8), 1366-1373.
[http://dx.doi.org/10.1111/j.1349-7006.2009.01195.x] [PMID: 19459851]
[78]
Jerabek, P.A.; Patrick, T.B.; Kilbourn, M.R.; Dischino, D.D.; Welch, M.J. Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: Potential in vivo markers of hypoxic tissue. Int. J. Rad. Appl. Instrum. [A], 1986, 37(7), 599-605.
[http://dx.doi.org/10.1016/0883-2889(86)90079-1] [PMID: 3021662]
[79]
Grierson, J.R.; Link, J.M.; Mathis, C.A.; Rasey, J.S.; Krohn, K.A. A radiosynthesis of fluorine-18 fluoromisonidazole. J. Nucl. Med., 1989, 30(3), 343-350.
[PMID: 2738663]
[80]
Lim, J.L.; Berridge, M.S. An efficient radiosynthesis of [18F]fluoro-misonidazole. Appl. Radiat. Isot., 1993, 44(8), 1085-1091.
[http://dx.doi.org/10.1016/0969-8043(93)90110-V] [PMID: 8358398]
[81]
Cherif, A.; Yang, D.J.; Tansey, W.; Kim, E.E.; Wallace, S. Rapid synthesis of 3-[18F]fluoro-1-(2-nitro-1-imidazolyl)-2-propanol ([18F]fluoromisonidazole). Pharm. Res., 1994, 11(3), 466-469.
[http://dx.doi.org/10.1023/A:1018937709835] [PMID: 8008718]
[82]
Oh, S.J.; Chi, D.Y.; Mosdzianowski, C.; Kim, J.Y.; Gil, H.S.; Kang, S.H.; Ryu, J.S.; Moon, D.H. Fully automated synthesis of [18F]fluoromisonidazole using a conventional [18F]FDG module. Nucl. Med. Biol., 2005, 32(8), 899-905.
[http://dx.doi.org/10.1016/j.nucmedbio.2005.06.003] [PMID: 16253816]
[83]
Chang, C.W.; Chou, T.K.; Liu, R.S.; Wang, S.J.; Lin, W.J.; Chen, C.H.; Wang, H.E. A robotic synthesis of [18F]fluoromisonidazole ([18F]FMISO). Appl. Radiat. Isot., 2007, 65(6), 682-686.
[http://dx.doi.org/10.1016/j.apradiso.2007.01.005] [PMID: 17379530]
[84]
Blom, E.; Koziorowski, J. Automated synthesis of [18F]FMISO on IBA Synthera®. J. Radioanal. Nucl. Chem., 2014, 299(1), 265-270.
[http://dx.doi.org/10.1007/s10967-013-2753-y]
[85]
Yokell, D.L.; Leece, A.K.; Lebedev, A.; Miraghaie, R.; Ball, C.E.; Zhang, J.; Kolb, H.; Elizarov, A.; Mahmood, U. Microfluidic single vessel production of hypoxia tracer 1H-1-(3-[18F]-fluoro-2-hydroxy-propyl)-2-nitro-imidazole ([18F]-FMISO). Appl. Radiat. Isot., 2012, 70(10), 2313-2316.
[http://dx.doi.org/10.1016/j.apradiso.2012.05.022] [PMID: 22871433]
[86]
Kumar, P.; Wiebe, L.I.; Asikoglu, M.; Tandon, M.; McEwan, A.J.B. Microwave-assisted (radio)halogenation of nitroimidazole-based Hypoxia markers. Appl. Radiat. Isot., 2002, 57(5), 697-703.
[http://dx.doi.org/10.1016/S0969-8043(02)00185-9] [PMID: 12433044]
[87]
Piert, M.; Machulla, H.J.; Picchio, M.; Reischl, G.; Ziegler, S.; Kumar, P.; Wester, H.J.; Beck, R.; McEwan, A.J.; Wiebe, L.I.; Schwaiger, M. Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J. Nucl. Med., 2005, 46(1), 106-113.
[PMID: 15632040]
[88]
Postema, E.J.; McEwan, A.J.B.; Riauka, T.A.; Kumar, P.; Richmond, D.A.; Abrams, D.N.; Wiebe, L.I. Initial results of hypoxia imaging using 1-αα-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA). Eur. J. Nucl. Med. Mol. Imaging, 2009, 36(10), 1565-1573.
[http://dx.doi.org/10.1007/s00259-009-1154-5] [PMID: 19430784]
[89]
Sorger, D.; Patt, M.; Kumar, P.; Wiebe, L.I.; Barthel, H.; Seese, A.; Dannenberg, C.; Tannapfel, A.; Osama Sabri, R.K.; Sabri, O. [18F]Fluoroazomycinarabinofuranoside (18FAZA) and [18F]Fluoromisonidazole (18FMISO): A comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors. Nucl. Med. Biol., 2003, 30(3), 317-326.
[http://dx.doi.org/10.1016/S0969-8051(02)00442-0] [PMID: 12745023]
[90]
Kumar, P.; Stypinski, D.; Xia, H.; McEwan, A.J.B.; Machulla, H-J.; Wiebe, L.I. Fluoroazomycin arabinoside (FAZA): Synthesis,2H and3H-labelling and preliminary biological evaluation of a novel 2-nitroimidazole marker of tissue hypoxia. J. Labelled Comp. Radiopharm., 1999, 42(1), 3-16.
[http://dx.doi.org/10.1002/(SICI)1099-1344(199901)42:1<3:AID-JLCR160>3.0.CO;2-H]
[91]
Kumar, P.; Wiebe, L.I.; Atrazheva, E.; Tandon, M. An improved synthesis of α-AZA, α-AZP and α-AZG, the precursors to clinical markers of tissue hypoxia. Tetrahedron Lett., 2001, 42(11), 2077-2078.
[http://dx.doi.org/10.1016/S0040-4039(01)00099-5]
[92]
Reischl, G.; Ehrlichmann, W.; Bieg, C.; Solbach, C.; Kumar, P.; Wiebe, L.I.; Machulla, H.J. Preparation of the hypoxia imaging PET tracer [18F]FAZA: Reaction parameters and automation. Appl. Radiat. Isot., 2005, 62(6), 897-901.
[http://dx.doi.org/10.1016/j.apradiso.2004.12.004] [PMID: 15799867]
[93]
Nandy, S.K.; Rajan, M.G.R. Simple, column purification technique for the fully automated radiosynthesis of [18F]fluoroazomycinara-binoside ([18F]FAZA). Appl. Radiat. Isot., 2010, 68(10), 1944-1949.
[http://dx.doi.org/10.1016/j.apradiso.2010.04.011] [PMID: 20478712]
[94]
Hayashi, K.; Furutsuka, K.; Takei, M.; Muto, M.; Nakao, R.; Aki, H.; Suzuki, K.; Fukumura, T. High-yield automated synthesis of [18F]fluoroazomycin arabinoside ([18F]FAZA) for hypoxia-specific tumor imaging. Appl. Radiat. Isot., 2011, 69(7), 1007-1013.
[http://dx.doi.org/10.1016/j.apradiso.2011.02.025] [PMID: 21420304]
[95]
Bouvet, V.R.; Wuest, M.; Wiebe, L.I.; Wuest, F. Synthesis of hypoxia imaging agent 1-(5-deoxy-5-fluoro-α-d-arabinofuranosyl)-2-nitroimidazole using microfluidic technology. Nucl. Med. Biol., 2011, 38(2), 235-245.
[http://dx.doi.org/10.1016/j.nucmedbio.2010.09.002] [PMID: 21315279]
[96]
Liu, T.; Karlsen, M.; Karlberg, A.M.; Redalen, K.R. Hypoxia imaging and theranostic potential of [64Cu][Cu(ATSM)] and ionic Cu(II) salts: A review of current evidence and discussion of the retention mechanisms. EJNMMI Res., 2020, 10(1), 33.
[http://dx.doi.org/10.1186/s13550-020-00621-5] [PMID: 32274601]
[97]
Vāvere, A.L.; Lewis, J.S. Cu-ATSM: A radiopharmaceutical for the PET imaging of hypoxia. Dalton Trans., 2007, 59(43), 4893-4902.
[http://dx.doi.org/10.1039/b705989b] [PMID: 17992274]
[98]
Burke, P.; Golovko, O.; Clark, J.C.; Aigbirhio, F.I. An automated method for regular productions of copper-64 for PET radiopharmaceuticals. Inorg. Chim. Acta, 2010, 363(6), 1316-1319.
[http://dx.doi.org/10.1016/j.ica.2010.01.038]
[99]
Yoshii, Y.; Yoneda, M.; Ikawa, M.; Furukawa, T.; Kiyono, Y.; Mori, T.; Yoshii, H.; Oyama, N.; Okazawa, H.; Saga, T.; Fujibayashi, Y. Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: Studies with mitochondrial DNA-less ρ 0 cells and cybrids carrying MELAS mitochondrial DNA mutation. Nucl. Med. Biol., 2012, 39(2), 177-185.
[http://dx.doi.org/10.1016/j.nucmedbio.2011.08.008] [PMID: 22033022]
[100]
Mokoala, K.M.G.; Lawal, I.O.; Jeong, J.M.; Sathekge, M.M.; Vorster, M. Radionuclide imaging of hypoxia: Where are we now? Special attention to cancer of the cervix uteri. Hell. J. Nucl. Med., 2021, 24(3), 247-261.
[PMID: 34954786]
[101]
Szajek, L.P.; Meyer, W.; Plascjak, P.; Eckelman, W.C. Semi-remote production of [ 64 Cu]CuCl 2 and preparation of high specific activity [ 64 Cu]Cu-ATSM for PET studies. Radiochim. Acta, 2005, 93(4), 239-244.
[http://dx.doi.org/10.1524/ract.93.4.239.64070]
[102]
Liu, T.; Redalen, K.R.; Karlsen, M. Development of an automated production process of [ 64 Cu][Cu (ATSM)] for positron emission tomography imaging and theranostic applications. J. Labelled Comp. Radiopharm., 2022, 65(7), 191-202.
[http://dx.doi.org/10.1002/jlcr.3973] [PMID: 35466453]
[103]
Kachur, A.V.; Dolbier, W.R., Jr; Evans, S.M.; Shiue, C.Y.; Shiue, G.G.; Skov, K.A.; Baird, I.R.; James, B.R.; Li, A.R.; Roche, A.; Koch, C.J. Synthesis of new hypoxia markers EF1 and [18F]-EF1. Appl. Radiat. Isot., 1999, 51(6), 643-650.
[http://dx.doi.org/10.1016/S0969-8043(99)00096-2] [PMID: 10581679]
[104]
Dolbier, W.R., Jr; Li, A.R.; Koch, C.J.; Shiue, C.Y.; Kachur, A.V. [18F]-EF5, a marker for PET detection of hypoxia: Synthesis of precursor and a new fluorination procedure. Appl. Radiat. Isot., 2001, 54(1), 73-80.
[http://dx.doi.org/10.1016/S0969-8043(00)00102-0] [PMID: 11144255]
[105]
Mahy, P.; Bast, D.M.; Leveque, H.P.; Gillart, J.; Labar, D.; Marchand, J.; Gregoire, V. Preclinical validation of the hypoxia tracer 2-(2-nitroimidazol-1-yl)-N-(3,3,3 [18F](trifluoropropyl)aceta-mide, [18F]EF3. Eur. J. Nucl. Med. Mol. Imaging, 2004, 31(9), 1263-1272.
[http://dx.doi.org/10.1007/s00259-004-1573-2] [PMID: 15197503]
[106]
van Loon, J.; Janssen, M.H.M.; Öllers, M.; Aerts, H.J.W.L.; Dubois, L.; Hochstenbag, M.; Dingemans, A.M.C.; Lalisang, R.; Brans, B.; Windhorst, B.; van Dongen, G.A.; Kolb, H.; Zhang, J.; De Ruysscher, D.; Lambin, P. PET imaging of hypoxia using [18F]HX4: A phase I trial. Eur. J. Nucl. Med. Mol. Imaging, 2010, 37(9), 1663-1668.
[http://dx.doi.org/10.1007/s00259-010-1437-x] [PMID: 20369236]
[107]
Sanduleanu, S.; Wiel, A.M.A.V.; Lieverse, R.I.Y.; Marcus, D.; Ibrahim, A.; Primakov, S.; Wu, G.; Theys, J.; Yaromina, A.; Dubois, L.J.; Lambin, P. Hypoxia PET imaging with [18F]-HX4-A promising next-generation tracer. Cancers , 2020, 12(5), 132.
[108]
Dubois, L.J.; Lieuwes, N.G.; Janssen, M.H.M.; Peeters, W.J.M.; Windhorst, A.D.; Walsh, J.C.; Kolb, H.C.; Öllers, M.C.; Bussink, J.; van Dongen, G.A.M.S.; van der Kogel, A.; Lambin, P. Preclinical evaluation and validation of [ 18 F]HX4, a promising hypoxia marker for PET imaging. Proc. Natl. Acad. Sci., 2011, 108(35), 14620-14625.
[http://dx.doi.org/10.1073/pnas.1102526108] [PMID: 21873245]
[109]
Zegers, C.M.L.; van Elmpt, W.; Wierts, R.; Reymen, B.; Sharifi, H.; Öllers, M.C.; Hoebers, F.; Troost, E.G.C.; Wanders, R.; van Baardwijk, A.; Brans, B.; Eriksson, J.; Windhorst, B.; Mottaghy, F.M.; De Ruysscher, D.; Lambin, P. Hypoxia imaging with [18F]HX4 PET in NSCLC patients: Defining optimal imaging parameters. Radiother. Oncol., 2013, 109(1), 58-64.
[http://dx.doi.org/10.1016/j.radonc.2013.08.031] [PMID: 24044790]
[110]
Peeters, S.G.J.A.; Zegers, C.M.L.; Lieuwes, N.G.; van Elmpt, W.; Eriksson, J.; van Dongen, G.A.M.S.; Dubois, L.; Lambin, P. A comparative study of the hypoxia PET tracers[¹⁸F]HX4, [18F]FAZA, and [18F]FMISO in a preclinical tumor model. Int. J. Radiat. Oncol. Biol. Phys., 2015, 91(2), 351-359.
[http://dx.doi.org/10.1016/j.ijrobp.2014.09.045] [PMID: 25491505]
[111]
Anderson, R. F; Smaill, J. B.; Patterson, A. V.; Ashoorzadeh, A.; Ackerley, D. F.; Copp, J. N. Compounds and methods for selective imaging and/or ablation. PCT Int. Appl. 2014.WO 2014007650 A1 20140109, INCOMPLETE.,
[112]
Verwer, E.E.; Zegers, C.M.L.; Elmpt, V.W.; Wierts, R.A.D.; Windhorst, A.D.; Mottaghy, F.M.; Lambin, P.; Boellaard, R. Pharmacokinetic modeling of a novel hypoxia PET tracer [18F]HX4 in patients with non-small cell lung cancer. Eur. J. Nucl. Med. Mol. Imag, 2016, 3(1), 30.
[113]
Turton, D.R.; Betts, H.M.; Dutton, D.; Perkins, A.C. Automated radiosynthesis of GMP quality [ 18 F]HX4 for PET imaging of hypoxia. Nucl. Med. Biol., 2015, 42(5), 494-498.
[http://dx.doi.org/10.1016/j.nucmedbio.2014.12.015] [PMID: 25725983]
[114]
Yang, D.J.; Wallace, S.; Cherif, A.; Li, C.; Gretzer, M.B.; Kim, E.E.; Podoloff, D.A. Development of F-18-labeled fluoroerythronitroimidazole as a PET agent for imaging tumor hypoxia. Radiology, 1995, 194(3), 795-800.
[http://dx.doi.org/10.1148/radiology.194.3.7862981] [PMID: 7862981]
[115]
Grönroos, T.; Eskola, O.; Lehtiö, K.; Minn, H.; Marjamäki, P.; Bergman, J.; Haaparanta, M.; Forsback, S.; Solin, O. Pharmacokinetics of [18F]FETNIM: A potential marker for PET. J. Nucl. Med., 2001, 42(9), 1397-1404.
[PMID: 11535732]
[116]
Hoigebazar, L.; Jeong, J.M.; Hong, M.K.; Kim, Y.J.; Lee, J.Y.; Shetty, D.; Lee, Y.S.; Lee, D.S.; Chung, J.K.; Lee, M.C. Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers. Bioorg. Med. Chem., 2011, 19(7), 2176-2181.
[http://dx.doi.org/10.1016/j.bmc.2011.02.041] [PMID: 21419635]
[117]
Bresser, P.L.; Vorster, M.; Sathekge, M.M. An overview of the developments and potential applications of 68Ga-labelled PET/CT hypoxia imaging. Ann. Nucl. Med., 2021, 35(2), 148-158.
[http://dx.doi.org/10.1007/s12149-020-01563-7] [PMID: 33400147]
[118]
Bresser, P.L.; Reed, J.; Sathekge, M.M.; Vorster, M. 68Ga-nitroimidazole PET/CT imaging of hypoxia in tuberculosis. J. Med. Radiat. Sci., 2022, 69(4), 518-524.
[http://dx.doi.org/10.1002/jmrs.603] [PMID: 35760568]

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