[en] Full text: The natural copper irradiation with deuterons produces the Cu-62, Cu-64 and Cu-66 radionuclides. Of two radioisotopes, those with deficiencies in neutrons, are applied in nuclear medicine diagnostic processes, mainly for the nuclear characteristic of the decay modes. The positron emitters, of short life mean Cu-62 (9.1 min, β⁺) and Cu(12.7 h), are radionuclides applied in radio pharmacological preparation for brain, core, blood flux studies. The radiochemical process consists in the de solution of the irradiated metallic copper target, in acid medium. The result solution, can be neutralized with a base or a buffer at wished pH. Using a deuteron beam of 4,2 ± 0,1 MeV energy has been obtained total yields of 1,103 ± 0,011 μCl/μAh medium for 62 Cu and of 0,148 ± 0,015 μCl/μAh for 64 Cu

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[en] Introduction: We synthesized and evaluated ⁶⁴Cu-labeled tetraiodothyroacetic acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because tetrac inhibits angiogenesis via integrin α_Vβ₃. Methods: Tetrac-PEG-DSPE and DOTA-PEG-DSPE were synthesized and formulated with other lipids into liposomes. The resulting tetrac/DOTA-liposomes were labeled with ⁶⁴Cu at 40 °C for 1 h and purified using a PD-10 column. ⁶⁴Cu-DOTA-liposomes were also prepared for comparison. Human aortic endothelial cell (HAEC) binding studies were performed by incubating the liposomes with the cells at 37 °C. MicroPET imaging followed by tissue distribution study was carried out using U87MG tumor-bearing mice injected with tetrac/⁶⁴Cu-DOTA-liposomes or ⁶⁴Cu-DOTA-liposomes. Results: HAEC binding studies exhibited that tetrac/⁶⁴Cu-DOTA-liposomes were avidly taken up by the cells from 1.02 %ID at 1 h to 11.89 %ID at 24 h, while ⁶⁴Cu-DOTA-liposomes had low uptake from 0.47 %ID at 1 h to 1.57 %ID at 24 h. MicroPET imaging of mice injected with tetrac/⁶⁴Cu-DOTA-liposomes showed high radioactivity accumulation in the liver and spleen. ROI analysis of the tumor images revealed 1.93 ± 0.12 %ID/g at 1 h and 2.70 ± 0.36 %ID/g at 22 h. In contrast, tumor ROI analysis of ⁶⁴Cu-DOTA-liposomes revealed 0.54 ± 0.08 %ID/g at 1 h and 0.52 ± 0.09 %ID/g at 22 h. Tissue distribution studies confirmed that the tumor uptakes of tetrac/⁶⁴Cu-DOTA-liposomes and ⁶⁴Cu-DOTA-liposomes were 1.75 ± 0.03 %ID/g and 0.36 ± 0.01 %ID/g at 22 h, respectively. Conclusion: These results demonstrate that tetrac/⁶⁴Cu-DOTA-liposomes have significantly enhanced tumor uptake compared to ⁶⁴Cu-DOTA-liposomes due to tetrac conjugation. Further studies are warranted to reduce the liver and spleen uptake of tetrac/⁶⁴Cu-DOTA-liposomes

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[en] The development of a new bifunctional chelator, which holds radio metals strongly in living systems, is a prerequisite for the successful application of disease-specific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu(Π) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator. TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive de protection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with ⁶⁴Cu and micro PET imaging was performed to follow the clearance pattern of the ⁶⁴Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with ⁶⁴Cu. TE2A was prepared in salt-free form cyclam in an overall yield of 74%. The micro PET images showed that ⁶⁴Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through on carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with ⁶⁴Cu in 94% yield within 30 min. TE2A can be used by itself as a bifunctional chelator without any further structural modification.

[en] Synthesis of intrinsically radiolabeled nanoparticles is an emerging concept in cancer theranostics and is expected to play an imperative role in translating nanotechnology research into clinical practice of nuclear medicine. In this study, we have developed a facile protocol for synthesis of small sized (4-5 nm diameter), water soluble, intrinsically radiolabeled ⁶⁴Cu metal nanoparticles capped within human serum albumin (HSA) scaffold (⁶⁴Cu- HSA nanocomposite). Detailed characterization of the as-synthesized nanoparticles was carried out by various analytical techniques to establish the colloidal and radiochemical stability, biocompatibility and suitability for clinical administration. The biological efficacy of the intrinsically radiolabeled ⁶⁴Cu- HSA nanocomposite was demonstrated by biodistribution studies in melanoma tumor bearing C57BL/6 mice, that showed rapid diffusion and accumulation of the radiotracer into tumor and clearance from the biological system by both renal and hepatobiliary routes. The promising results obtained in this study suggest that this strategy could be employed to facilitate clinical translation of a new class of biocompatible radiotracers derived from metalbased nanoparticles for use in cancer theranostics. (author)

[en] Synthesis of intrinsically radiolabeled nanoparticles is an emerging concept in cancer theranostics and is expected to play an imperative role in translating nanotechnology research into nuclear medicine industry. In order to reduce reliance on cyclotron produced ⁶⁴Cu (t_1/2 = 12.7 h, EC 45 %, b⁺ 17.9 %, b^- 37.1 %) and increase global accessibility of this radioisotope for preclinical and clinical investigations, we have explored the feasibility of using neutron activated ⁶⁴Cu produced in research reactors for potential use in cancer theranostics. A viable strategy has been developed for production of ⁶⁴Cu in medium flux research reactors and its utilization toward industrial-scale (GBq level) synthesis of intrinsically radiolabeled ⁶⁴CuS nanoparticles (∼ 30 nm particle size). The synthesis procedure was easily executable in a hot cell equipped with suitable remotely operable gadgets and ⁶⁴CuS nanoparticles could be synthesized in a form suitable for clinical administration. The stability of the nanoparticles under physiological conditions was established by detailed in vitro studies in phosphate buffered saline (PBS) and mouse serum media. The biological efficacy of intrinsically radiolabeled ⁶⁴CuS nanoparticles was studied in C57BL/6 mice bearing melanoma tumors. The results of the biodistribution studies revealed significant tumor uptake (4.64 ± 1.71 %ID/g) within 4 h postinjection, with good tumor-to-background contrast. Collectively, the promising results obtained in this study suggest that the concept of intrinsically radiolabeled nanoplatforms can be employed to facilitate widespread utilization of neutron activated ⁶⁴Cu in nuclear medicine industry. (author)

[en] The use of radioisotopes of high specific activity is of great importance in studies on distributions of radioactive substances in living beings. In countries where only low thermal neutron flux reactors are available the production of ⁶⁴Cu of specific activity is carried out by the Szilard-Chalmers process, which involves the braking of the chemical bondings of the compounds. In this work, experiments were carried out by irradiating the compound bis-[N-benzoil-phenylhydroxylaminate] copper (II) in IEA-R₁ nuclear reactor in a thermal neutron flux of 5x10¹² n/cm². Samples without and with thermal treatment before and/or after irradiation were tested. Samples without pre-heating and with thermal annealing were irradiated for 6,5 h and yields of ⁶⁴Cu of about 3,900 MBq/mg Cu were obtained 21 h after the end of irradiation. The results in this work show the possibility of the preparation of ⁶⁴Cu of high specific activity with that compound by the Szilard-Chalmers process. The faseability of its production will depend on the optimization of the chemical processing and on the preparation of ⁶⁴Cu in a suited form for medical applications. (author)

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[en] Using a ⁶⁴Cu complex, we obtained human basal ganglia scans in three normal volunteers and in one patient with Wilson's disease with an oral dose of 1 mCi. The method with this new radioactive compound was simple and safe and the results were very encouraging. (U.S.)