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

Backgraound: 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.

[61Cu]-diacetyl-bis (N4-methylthiosemicarbazone) ([61Cu]-ATSM) was prepared using house-made ATSM ligand and [61Cu]CuCl2 produced via the natZn(p,x)61Cu (180¼A proton irradiation, 22MeV, 3.2h) and purified by ion chromatography method. [61Cu]-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 61Cu and showed a radionuclidic purity higher than 99%. The rest of activity was attributed to 60Cu (0.23%). [61Cu]-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. [61Cu]-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.