Title:Editorial Review of 2014
Volume: 7
Issue: 1
Author(s): Sean L. Kitson and Luigi Mansi
Affiliation:
Abstract: Since the conception of the journal Current Radiopharmaceuticals in January 2008, we have been inundated with a variety
of research articles ranging from discussions on the use of radiopharmaceuticals in imaging to drug discovery and targeted
therapies. All these articles have been peer reviewed by members of editorial board including guest editors. Here, I would
personally like to take this opportunity to thank everyone on the editorial board who has volunteered his/her time to review the
various articles that we have received and also the editorial staff at Bentham Science.
Current Radiopharmaceuticals has caught the interest of many scientists working in Nuclear Medicine. The journal owes its
success to all the authors who have submitted high quality manuscripts sharing in-depth knowledge in the area of
radiopharmaceuticals to produce thematic issues. The idea behind thematic ‘Hot Topic’ issues is to generate maximum impact
factor for the published material in that particular subject area of radiopharmaceuticals and nuclear medicine.
A new feature for 2014 submission of manuscripts to the journal will include a graphical abstract to summarize the contents
of the article in a concise pictorial form, which will enable rapid viewing of the journals' contents and help capture the readers’
attention.
The sixth volume of Current Radiopharmaceuticals contains articles on a wide range of hot topics. The efforts and
determination of the editorial board and guest editors have helped promote the journal at various scientific meetings owing to
its MEDLINE status since 2011. Our next goal is to earn soon an impact factor for the journal. In this ‘mission’, the help in
diffusing our articles submitted by associate and guest editors, members of the editorial board, authors and interested readers
will be of core importance.
In this editorial review, I have summarized all the abstracts from 2013 issues 1 to 4.
The first article of the year by Latli et al. is entitled as ‘Sodium-Proton Exchanger Isoform-1: Synthesis of a Potent Inhibitor
Labeled with Deuterium and Carbon-14’, which gives an account of the synthesis of carbon-14 and deuterium labeled N-[4-(1-
acetyl-piperidin-4-yl)-3-trifluoromethyl-benzoyl]-guanidine, a potent sodium-proton exchanger NHE-1 inhibitor. These NHEs
are plasma membrane proteins that are essential in the regulation of intracellular pH of the myocardium and the labeled NHE-1
inhibitors have been used to evaluate ADME studies.
The next article ‘Synthesis and Evaluation of 99mTc Chelate-conjugated Bevacizumab’ by Camacho et al. discusses the role
of the monoclonal antibody bevacizumab as a possible imaging agent against vascular endothelial growth factor (VEGF) in
various animal models. The modified imaging agent 99mTc-HYNIC-bevacizumab was evaluated using the adenocarcinoma
animal model. The authors concluded that this SPECT imaging agent has potential in tumor imaging at the preclinical level.
In the following article on ‘Biodistribution and Dosimetry of 177Lu-tetulomab, a New Radioimmunoconjugate for Treatment
of Non-Hodgkin Lymphoma’ by Repetto-Llamazares et al., the authors have evaluated the biodistribution of the following anti-
CD37 radioimmunoconjugates177Lu-tetraxetan-tetulomab and 177Lu-tetraxetan-rituximab against free 177Lu. They used nude
mice implanted with Daudi lymphoma xenografts and suggested that a higher tumor radiation dose can be reached using177Lutetraxetan-
tetulomab in the clinic arena.
In the article subjected as ‘Novel 99mTc-labeled Diphosphonic Acid as Potential Bone Seeking Agent: Synthesis and
Biological Evaluation’ by Qiu et al., the authors have managed to prepare a novel zoledronate derivative, BIBDP labeled with
99mTc in high radiochemical purity with a good stability in vitro profile. This imaging agent showed a high specificity and
efficacy in bone uptake compared to99mTc-MDP and 99mTc-ZL. The clear images were obtained after 1 h from using SPECT
and this indicated that 99mTc- BIBDP has great potential for bone imaging.
Subsequently, in the next article with the title ‘Peptide Imaging with Somatostatin Analogs: More than Cancer Probes’ by
Cascini et al., the authors have studied the imaging of neuroendocrine tumors (NETs) using the diagnostic tool Somastostatin
(SS) scintigraphy (SRS). NETs and a number of non-neoplastic cells have been shown to possess a high affinity for binding
between SS and its receptors (sstr). Numerous SS analogs have been studied and the pentetreotide labeled with In-111 has been
described the one most widely used for imaging due to its high affinity towards sstr 2 and 5. The development of these SPECT
imaging agents will enable the detection of NET and other disease processes.
Furthermore, the article ‘Bone Metastases Radiopharmaceuticals: An Overview’ by Cuccurullo et al. reviews a number of
radiolabeled compounds that are successfully used to detect and/or characterize bone metastases. This approach uses two
radionuclide functional techniques scintigraphy and positron emission tomography (PET) imaging. Therefore, the diagnosis and
evaluation of skeletal metastases require a combined approach of different diagnostic methods using the appropriate
radiopharmaceutical.
The last article in issue 1 is by Peter Mitrasinovic entitled as, ‘Some Implications of Receptor Kinase Signaling Pathway for
Development of Multi-targeted Kinase Inhibitors.’ In this article, the author evaluates the various radiolabeled agents for PET
and SPECT imaging against the epidermal growth factor receptors (EGFRs), especially towards the next generation of multitargeted
kinase inhibitors. Issue 2 begins with the article on ‘Radionuclide Antibody-Conjugates, a Targeted Therapy towards Cancer’ by Kitson et al.
In this article, they have evaluated the use of monoclonal antibodies (mAbs), peptide conjugates and various chemical
compounds to develop targeted therapies towards the treatment of oncological diseases. These TAT bio-vectors are able to
transport a dose of alpha particles to destroy cancer cells. Radionuclide antibody-conjugates (RACs), labeled with beta emitters,
have already been used in humans. The article concludes on the theory of tumor-antivascular- alpha-therapy (TAVAT) which
may give rise to an alternative mechanism for TAT.
This led to the article ‘Generator Breakthrough and Radionuclidic Purification in Automated Synthesis of 68Ga-DOTANOC’
by Belosi et al.; in this research, the authors have studied the efficacy of cationic pre-purification using commercial STRATAX-
C, as well as distribution of the 68Ge contaminant during the synthesis of labeled peptides. The generator waste, STRATA-XC
purification cartridge, synthesis waste and the final product were quantitatively analyzed by high resolution gamma ray
spectrometry. They concluded that the synthesis using modular automated system produces 68Ga-DOTANOC, with limited user
intervention. The 68Ge content in the final formulation was below 2x10-7% thus satisfying quality prerequisites for the
radiopharmaceutical preparations.
The next article is entitled as ‘Comparing High LET 227Th- and Low LET 177Lu-trastuzumab in Mice with HER-2 Positive
SKBR-3 Xenografts’ by Abbas et al.; in this study, the authors set out to compare the biodistribution, normal tissue toxicity and
therapeutic effect of the alpha-particle emitting 227Th-trastuzumab and the beta-particle emitting 177Lu-trastuzumab. These
studies were carried out in mice with HER2- expressing SKBR-3 breast cancer xenografts. They concluded that thexenograft
model gave a higher RBE for 227Th-trastuzumab compared to177Lu-trastuzumab, while the therapeutic index of 177Lutrastuzumab
was superior to that of 227Th-trastuzumab.
Then comes the article ‘[131I]IAZA as a Molecular Radiotherapeutic (MRT) Drug: Wash-Out with Cold IAZA Accelerates
Clearance in a Murine Tumor Model’ by Mercer et al.; here the authors have demonstrated in animal models that a wash out
procedure using [131I]IAZA as a Molecular Radiotherapeutic (MRT) drug could be utilized in the treatment of tumor hypoxia.
The drawback to this approach was the high radioactivity level in the blood. Therefore to modulate the clearance of bound and
free radioactive IAZA, non-radioactive (cold) IAZA was administered to the Balb/C EMT-6 murine tumor model. After 1 hour,
an injection of high specific activity [125I][IAZA was administered in the Balb/C EMT-6 murine tumor model. This ‘wash out’
procedure reduced the concentrations of radioactivity by at least 40% in all tissues especially in the kidney and liver, and least
at the tumor site.
Next is the article entitled as ‘The Dilemma of Localizing Disease Relapse After Radical Treatment for Prostate Cancer:
What is the Value of the Actual Imaging Techniques?’ by Schiavina et al.; this paper seeks to evaluate the management of
patients with BCR after radical treatment of prostate cancer from the urologist point of view. They concluded that Multiparametric
Magnetic Resonance Imaging may have a role in the early phase of PSA relapse. Conventional imaging, such as
bone scan and CT, is not suggested in the initial phase of BCR. Recently, it has been reported that PET/CT allows changes to
the therapeutic strategy (from palliative to curative treatment and vice-other biomolecules with theversa) in about 20% of cases. In recent years, the new
radiotracer 18F-FACBC has been proposed as a possible alternative radiopharmaceutical to detect prostate cancer relapse.
In the article entitled as ‘What is Currently the Best Radiopharmaceutical for the Hybrid PET/CT Detection of Recurrent
Medullary Thyroid Carcinoma?’ by Slavikova et al., the authors have voyaged to review literature evidence about the efficacy
and tolerance of radiopharmaceuticals towards three targets of PET/CT imaging (glucose metabolism, bio-amines metabolism
and somatostatin receptors). They also included bone scintigraphy which was recommended in the Guidelines of European
Society for Medical Oncology (ESMO).
The concluding article of issue 2 comes with the title ‘Targeted Alpha Therapy with 227Th-trastuzumab of Intraperitoneal
Ovarian Cancer in Nude Mice’ by Heyerdahl et al.; the aim of this current study is to investigate the therapeutic effect of 227Thradioimmunotherapy
on intraperitoneally growing human bioluminescent HER2 positive ovarian cancer cells. They concluded
that targeted alpha therapy using 227Th-trastuzumab towards human SKOV3-luc-D3 cells growing intraperitoneally in nude
mice was clearly superior to unlabeled trastuzumab therapy. These results warrant further studies of 227Thradioimmunotherapy
used as adjuvant treatment and for metastatic cancer.
The leading article in issue 3 is entitled as ‘New Issues for Copper-64: from Precursor to Innovative Pet Tracers in Clinical
Oncology’ by Evangelista et al.; in this paper, the authors have analyzed the potential applications for copper-64 as a PET
imaging agent in the clinical oncology setting. Copper-64 has been reported to emit both positrons and β-particles and to be
suitable for the labeling of numerous molecules that could be used for radionuclide imaging with applications in radionuclide
therapy. Unfortunately, due to limited available data on radiotracers labeled with radio-copper and in particular on the use of
64CuCl2 in cancer patients further investigations are required.
The second article on, ‘Gadolinium-Deferasirox-D-Glucosamine: Novel Anti-Tumor and MR Molecular (Theranostic)
Imaging Agent’ by Amanlou et al. outlines the reason for their study to evaluate the imaging agent gadolinium-deferasirox-Dglucosamine.
Thisnon-radioactive labeled glucose analog to image cancer tissue and heart function was carried out using MRI
instead of PET imaging. This approach would circumvent the use of tracers such as 18FDG in making a diagnosis of cancer and
therefore consideration must be given to this new MRI imaging agent. The third article on ‘Mixed Tridentate π-Donor and Monodentate π-Acceptor Ligands as Chelating Systems for Rhenium-
188 and Technetium-99m Nitrido Radiopharmaceuticals’ by Boschi et al. presents a new molecular metallic fragment for
labeling biologically active molecules with 99mTc and 188Re. The system was composed of a combination of tridentate π-donor
and monodentate π-acceptor ligands bound to a [M Ξ N]2+ group (M = 99mTc, 188Re) in a pseudo square-pyramidal geometry.
The investigation was further extended to comprise a series of ligands formed by simple combinations of two basic amino acids
or pseudo-amino acids to yield potential tridentate chelating systems having [S, N, S] and [N, N, S] with π-donor atoms.
Labeling yields and in vitro stability were investigated using different ancillary ligands. The results showed that SNS-type
ligands afforded the highest labeling yields and the most robust 3+1 nitrido complexes with both 99mTc and 188Re. Therefore,
this new chelating system can be conveniently employed for labeling peptides and other biomolecules with the [M ΞN]2+ group.
The following article entitled as ‘Cellular Toxicity and Apoptosis Studies in Osteocarcinoma Cells, a Comparison of 177Lu-
EDTMP and Lu-EDTMP’ by Kumar et al. outlines a study regarding the cell uptake of 177Lu-EDTMP agent in osteocarcinoma
cell lines to investigate the underlying mechanism of cellular toxicity. These studies indicate that the 177Lu-EDTMP binds to
mineralized bone cells and induces apoptotic cell death in MG63 cells.
Finally, the last article of issue 3 on ‘Targeted Radionuclide Therapy - An Overview’ by Dash et al.; discusses the use of
Radionuclide therapy (RNT) based on the concept of delivering cytotoxic levels of radiation to diseased sites. The primary
objective was to provide an overview on the role of radionuclide therapy in the treatment of different diseases such as
polycythemia, thyroid malignancies, metastatic bone pain, radiation synovectomy, hepatocellular carcinoma (HCC),
neuroendocrine tumors (NETs), non-Hodgkin’s lymphoma (NHL) and others. The article discusses many factors in choosing
the appropriate radionuclide based on its availability, the type of emissions, linear energy transfer (LET), and physical half-life.
Issue 4 starts with the article entitled as ‘Radiolabeled Peptides for Alzheimer’s Diagnostic Imaging: Mini Review’ by
Barrios-Lopez et al.; in this paper, the authors have reviewed the use of molecular imaging tools to provide an in vivo
visualization of Aβ plaques in the pathology of Alzheimer’s disease (AD). The specific identification of amyloid plaques would
allow a more accurate prognosis and ensure more effective clinical trials of anti-amyloid agents at an earlier disease stage. The
emphasis of this review was on the development of Aβ peptide radiopharmaceuticals. They also included nano-carriers based
on Molecular Trojan horses or nano-particles for applications towards in vivo amyloid imaging in AD. Two of the priorities for
the treatment of AD are the early detection and accurate chart progression of the accumulation of Aβ plaques in human brains.
The next article ‘SPECT Radiopharmaceuticals for Dementia’ by Guidotti et al. discusses various imaging tools used to
study neurodegenerative diseases with an emphasis on SPECT. The use of SPECT tracers was thought to be in decline
compared to PET imaging in neurology. Today, a wide range of novel SPECT radiotracers, dual-SPECT tracer techniques and
receptor targeting designed radiopharmaceuticals are currently being utilized for studying various disease processes. The
development of new hybrid SPECT imaging systems integrated with other imaging modalities (e.g. MRI, CT, ultrasound
techniques) has contributed to the improvement of the image resolution. Therefore, all of these improved conditions especially
those towards neuroimaging bring renewed interest in the development of new SPECT radiopharmaceuticals towards clinical
applications.
The title ‘Risk Assessment and Economic Impact Analysis of the Implementation of New European Legislation on
Radiopharmaceuticals in Italy: The Case of the New Monograph Chapter Compounding of Radiopharmaceuticals
(PHARMEUROPA, Vol. 23, No. 4, October 2011)’ by Chitto et al. explains the Good Radiopharmaceuticals Practice (NBP)
implementation which shows an extremely positive impact on risk management for both patients receiving Nuclear Medicine
services and the healthcare organization. The implementation of the ministerial decree will allow for greater detectability of and
control over a number of critical elements, paving the way for risk management and minimization.
In the article ‘PET Radiotracers for Molecular Imaging in Dementia’, by Baskin et al., the authors review the current
literature focusing on the PET radiotracers used for molecular imaging in dementia. The emphasis was on molecular imaging as
a tool to collect relevant information to gain an overall accurate diagnosis, treatment and response monitoring towards
dementia.
The penultimate article on ‘Monoclonal Antibodies: Application in Radiopharmacy’ by Ligiero et al. reviews the data on
the use of monoclonal antibodies in the last 40 years. All the data collected was summarized to reveal that this new class of
medicine may bring great advance in the field of radiopharmacy, oncology and imaging.
The final article of issue 4 entitled as ‘Thyroid Cancer Incidence 25 Years after Chernobyl, in a Romanian Cancer Center:
Is it a Public Health Problem?’ by Piciu et al. discusses the increase of thyroid cancer (TC) throughout the world during the
last decade. This may be due to more people being exposed to ionizing radiation. To investigate this further, the authors
analyzed various patients’ records with TC who were treated at the Institute of Oncology Cluj-Napoca, Romania. They
performed a comparative analysis of the database at intervals of 10, 20 and 25 years after the 1986 Chernobyl nuclear accident.
From the analysis of the data, they found changes in histological profiles and tumor sizes. They implied that, in addition to
nuclear fallout, highly sensitive thyroid diagnostic procedures were responsible for this increase in reported incidence. This
appears to be driven by improved discovery of small (<1 cm) preclinical tumors. A further investigation of these observations is
needed to address any public health concerns. Moreover, we have some very interesting articles and hot topic issues, which will be published in the forthcoming issues.
Hot topics for 2014 include ‘Lutetium-177 Labeled Therapeutics: Emerging Importance For Cancer Treatment And Therapy Of
Chronic Disease’; ‘Radiopharmaceuticals For The Diagnosis and Treatment of Cancer’ and ‘The Use Of Positron Emission
Tomography In External Beam Therapy Dose Planning.’
The journal is gaining pace and so is its reputation amongst researchers in pharmaceutical (imaging) companies, institutions
and universities; all of this will lead to the future success of Current Radiopharmaceuticals. Here we remember Dirk Roeda
who passed away on July 19, 2013 and was an active editorial board member of Current Radiopharmaceuticals since 2010
having completed two thematic issues on [18F] Fluoride Radiochemistry with Micheal Kassiou and Frédéric Dolle.
