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Radiochemistry for Preclinical Imaging Studies
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Although subject to much research, the PET radiochemistry of copper-64 is still dominating the preclinical field rather than the clinical field. There seems to be a combination of reasons for this. Presumably, it is because of a nontrivial radionuclide-manufacturing process, the limiting physical properties of 64Cu, and a less favorable biodistribution of the tracers. The latter can be related to in vivo demetallation issues. Figure 16.23 compiles a short list of macrocycles suitable for complexing 64Cu for conjugation to biomacromolecules. As in all radiometal complex compounds, in vivo stability is of particular concern. Here, the best results can be achieved if the macrocyclic ligand neutralizes the charge of Cu(II) to form a complex without net charge. For example, NOTA would be a better choice than DOTA or TETA. This has been shown for 64Cu labeling of bombesin and in the corresponding in vivo studies (Prasanphanich et al. 2007). The best stability has been observed for ligands that allow for a higher level of metal ion shielding against hydrolysis, for instance, in the cross-linked CB-TE2A or the cryptand DIAMSAR. Both systems have been employed to prepare preclinical RGD peptide tracers (Wei et al. 2009). More recently, TRAP conjugates have been also recommended for labeling peptides with 64Cu (Šimeček et al. 2012).
Multimodality management of metastatic neuroendocrine tumors
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
Parissa Tabrizian, Yaniv Berger, Daniel M. Labow
Indium-111 octreotide scintigraphy has a lower sensitivity (69%–86%) and a higher cost for detecting NETs than do PET or CT scans using gallium-68-labeled somatostatin analogs [35]. The isotope copper 64 DOTATE has been shown to be more sensitive than indium-111 or 68Ga. The highest sensitivity and specificity for NET-LM (82%–100% and 67%–100%) or extrahepatic metastasis in low-grade NETs (85%–96% and 67%–90%) have been demonstrated with the use of gallium-68 somatostatin receptor PET or CT scans [35, 40, 41]. Lesions not identified on CT or MRI can be detected in up to 67%, and therefore candidates better selected for curative treatment [35].
Long Lived and Unconventional PET Radionuclides
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Jason S. Lewis, Rajendra K. Singh, Michael J. Welch
The copper PET nuclides (60Cu, 61Cu, 62Cu, and 64Cu) have been extensively studied because of their range of decay schemes allowing for versatile and selective use of the copper nuclide depending on the application (1,5). Among all the copper PET nuclides, 64Cu, with a half-life of 12.7 hours, is ideally suited for PET studies that can be conducted over 2 to 3 days. Copper-64 decays 19% by positron emission and has a β+ maximum energy of 0.66 MeV with an average energy of 0.28 MeV. It also decays by electron capture (38%) and β− (43%) and has therefore been studied as both a diagnostic and a therapeutic radionuclide (5). Since 64Cu has a β+ maximum energy of 0.66 MeV, which is almost identical in energy to the most widely used PET nuclide 18F, which has a β+ maximum energy of 0.63 MeV, the resulting PET images are of very good quality (Fig. 2) (8). The use of 64Cu has dramatically increased in the past decade and its production has now been reported by academic sources in the United States (9,10), Europe (11,12), and Japan (13). A number of commercial sources are also producing and supplying 64Cu in North America (e.g., MDS Nordion and Trace Radiochemical Life Sciences) and Europe (e.g., ACOM, Italy).
Inhibitors of prostate-specific membrane antigen in the diagnosis and therapy of metastatic prostate cancer – a review of patent literature
Published in Expert Opinion on Therapeutic Patents, 2021
Hyunsoo Ha, Hongmok Kwon, Taehyeong Lim, Jaebong Jang, Song-Kyu Park, Youngjoo Byun
This review discusses 32 patents for PSMA-targeted imaging and therapeutic agents based on the Lys-urea-Glu or Glu-urea-Glu structure, published from January 2017 to June 2020 (Table 1). Most of the patented PSMA-targeted agents presented strong PSMA-inhibitory activity with IC50 or Ki values in the nanomolar range and high tumor/blood ratio (>5) in in vivo and ex vivo experiments. Structural changes in the patented compounds were found on the S1 accessory pocket and tunnel region, keeping the glutamate-binding S1ʹ site unchanged. Notably, the optimization of the linker and introduction of radiometal-chelating moieties was achieved by utilizing the flexibility of the tunnel region. For the diagnosis of metastatic PCa, PET imaging probes radiolabeled with fluorine-18, copper-64, and gallium-68, as well as SPECT probes labeled with technetium-99m, have demonstrated promising results in animal and human studies. Therapeutic agents labeled with α- or β-emitting radionuclides have increased the median survival time and decreased tumor size in in vivo experiments. In addition, conjugate compounds that link Lys-urea-Glu with cytotoxic agents have been synthesized and evaluated for their anti-tumor activities.
Theranostic approaches in nuclear medicine: current status and future prospects
Published in Expert Review of Medical Devices, 2020
Luca Filippi, Agostino Chiaravalloti, Orazio Schillaci, Roberto Cianni, Oreste Bagni
Radiopharmacy is a field that is expected to rapidly evolve in the next few years. In this respect, the radionuclide copper-64 (64Cu) is gaining more and more attention in the scientific community. Copper is an essential element in many metabolic processes involving cell differentiation, metabolism, and growth. Furthermore, human copper transporter 1 (CTR1), a transmembrane protein responsible for copper intracellular incorporation, was found to be overexpressed in many malignancies. 64Cu is a cyclotron-produced radionuclide with an intermediate half-life (12.7 h) that decays by both positronic and beta-particles emission, making it suitable for theranostic applications. The radiopharmaceutical 64CuCl2, a substrate for CTR1, is under investigation with promising results as a potential theranostic agent in several pre-clinical and clinical trials regarding tumors such as melanoma or prostate cancer [90,91].
Novel ligands and modulators of triggering receptor expressed on myeloid cells receptor family: 2015-2020 updates
Published in Expert Opinion on Therapeutic Patents, 2021
Harbinder Singh, Vikrant Rai, Sunil K. Nooti, Devendra K. Agrawal
Michelle and colleagues [78] reported for the first-time labeled probe (agonist antibody) by targeting TREM-1 for the detection of inflammatory disease conditions. The labeled probe was developed by using copper-64 (64Cu-DOTA TREM-1 probe) that can selectively bind to TREM-1 with high affinity in vitro and in vivo and can be detected by Positron Emission Tomography imaging. Particularly, it was revealed that the labeled probe can link directly to the extracellular domain of TREM-1 through lysine amino acid [78].