[Possibility of production of a novel radiopharmaceutical for identification of hypoxic tissues]

Hypoxia is an important determinant for biological behavior of malignant solid tumors. In vitro and in vivo studies have shown that tumor hypoxia is associated with an increased likelihood of local recurrence and distant metastasis, as well as resistance to radiation therapy and certain types of chemotherapy. Studies have shown that some copper-bis thiosemicarbazones especially, Cu-ATSM accumulates avidly in hypoxic cells, but washes out rapidly from normoxic cell. [[61]Cu]-diacetyl-bis [N4-methylthiosemicarbazone] [[61]Cu]-ATSM] was prepared using house-made ATSM ligand and [[61]Cu]CuCl[2] produced via the [nat]Zn[p,x] [61]Cu [180[1/4]A proton irradiation, 22MeV, 3.2h] and purified by ion chromatography method. [[61]Cu]-ATSM was administered into normal and tumor bearing rodents up to 180 minutes followed by biodistribution and co-incidence imaging studies. Radionuclidic control showed the presence of 67.41[4.23%], 282.96[12.2%], 373[2.15%], 511[122.9%], 656[10.77%], 1186[3.75%] keV-rays from [61]Cu and showed a radionuclidic purity higher than 99%. The rest of activity was attributed to [61]Cu [0.23%]. [[61]Cu]-ATSM radiochemical purity was >99% shown by HPLC and RTLC methods. A significant difference was observed between tumor and non tumor accumulation. The method used in this research for the production and chemical separation of 61Cu was simple and cost effective. [[61]Cu]-ATSM is PET radiopharmaceutical for hypoxia imaging with an intermediate half life, and our experiments on this radiopharmaceutical have shown satisfactory results, suitable for future PET studies in human

Production, quality control and imaging of [64]Cu-ATSM in healthy rabbits for clinical applications

[[64]Cu]diacetyl-bis[N[4]-methylthiosemicarbazone] [[[64]Cu]ATSM] is a well-established hypoxia imaging tracer with reproducible production and significant specifity. In this work the high yield production and quality control as well as imaging studies in healthy rabbits is reported. Copper-64 produced via the [68]Zn[p, alpha n] [64]Cu nuclear reaction [30 MeV protons at 180 micro A] was used for the preparation of [[64]Cu]diacetyl-bis[N4-methylthiosemicarbazone][[ [64]Cu]ATSM]. Followed by quality control and administration to healthy rats as well as healthy rabbits for biodistribution and imaging studies respectively. [64]Cu[2+] [500 mCi, separation yield> 95%, radionuclide purity>96%] was used for [[64]Cu]ATSM production [radiochemical purity>99%, specific activity of 300 Ci/mmol] followed by administration to healthy rabbits and coincidence imaging demonstrating uptake in liver, kidney and bowel as shown by other reports in various rodents and human. [[64]Cu]ATSM radiopharmaceutical is produced and now available in large quantities for research and/or clinical trials in the country

Preliminary imaging studies of [[61]Cu] diacetyl-bis [N[4]-methylthiosemi-carbazone] in normal and hypoxic tumor models

[[61]Cu] diacetyl-bis [N[4] -methylthiosemicarbazone] [[[61]Cu] ATSM] is a well-established hypoxia imaging tracer with simple production and significant specifity. In this work the accumulation of the tracer is studied in wild-type, necrotic and hypoxic fibrosarcoma tumors. [[61] Cu] ATSM was prepared using ATSM ligand and [[61]Cu] CuOAc followed by i.v. administration and imaging studies in wid-type rats and hypoxic fibrosarcoma-bearing mic.e [[61] Cu] ATSM with high radiochemical purity [>99%, HPLC, RTLC] was injected to wild-type rats as well as hypoxic and necrotic fibrosarcoma-bearing mice followed by imaging up to 3 hours. [[61] Cu] ATSM was mainly accumulated in liver, as well as kidney and bladder and less but still significant in brain of wild-type rats. A significant and hypoxia-specific tumor/non tumor ratio in hypoxic models was observed by co-incidence imaging 2h post inection, while in necrotic and 12-week tumor-induced mice very slight tumor uptakes were detected. [[61]Cu] ATSM is a positron emission tomography [PET] radiotracer for selective tumor hypoxia imaging from necrotic and proliferative tumors

Biodistribution of [64 Cu] pyruvaldehyde-bis [N4-methylthiosemicarbazone] complex in fibrosarcoma-bearing rats

[64]Cu-pyruvaldehyde-bis [N[4]-methylthiosemicarbazone] [64]Cu-PTSM] is one of the most important copper radiopharmaceuticals used in clinical experiments. In this work, copper-64 [T[1/2]=12.33 h] production has been presented followed by the synthesis of the complexing agent, PTSM, and its structure was confirmed by common spectroscopic methods followed by radiolabeling with [64] Cu-actetate. The tracer was finally administered to fibrosarcoma-bearing rats and the biodistribution was determined in critical tissues as well as tumor. The final radiopharmaceutical solution underwent common quality control tests for animal injection a radiochemical purity >95% was determined. A significant tracer tumor uptake was observed 2 hours post injection. Tumonmuscle and tumonblood ratios were shown to be 8 and 6 respectively. [64]Cu-PTSM prepared in this report is a good candidate for tumor therapy as well as diagnosis for national use