Preparation of [61Cu]-2-acetylpyridine thiosemicarbazone complex as a possible PET tracer for malignancies

Due to the interesting anti-proliferative properties of copper-thiosemicarbazone complexes, the production of a 61Cu-labeled thiosemicarbazone, i.e. 2-acetylpyridine thiosemicarbazone (APTS) was investigated. Copper-61 (T1/2=3.33h) was produced via the 64Zn(p,α)61Cu nuclear reaction using a natural zinc target irradiated with 22MeV protons for 500μAh. The 61Cu was separated from the irradiated target material by a two-step method and converted to acetate; this yielded a final activity of 222GBq (6.0Ci), with a radiochemical yield of >95%. The 61Cu-acetate was mixed with 2-acetylpyridine thiosemicarbazone for 30min at room temperature to yield [61Cu]APTS with a radiochemical yield of more than 80%. Colorimetric methods showed that residual chemical impurities in the product were below the accepted limits. Radio thin layer chromatography (RTLC) showed a radiochemical purity of more than 99% after C18 column chromatography. A specific activity of about 370-740MBq/mmol (10-20Ci/mmol) was obtained. The stability of the final product was checked in the absence and presence of human serum at 37oC for up to 3h. The partition coefficient of the final complex was also determined