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

Abstract

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 ( T 1 / 2 = 3.33 h ) was produced via the 64Zn(p,α) 61Cu nuclear reaction using a natural zinc target irradiated with 22 MeV protons for 500 μAh. The 61Cu was separated from the irradiated target material by a two-step method and converted to acetate; this yielded a final activity of 222 GBq (6.0 Ci), with a radiochemical yield of >95%. The 61Cu–acetate was mixed with 2-acetylpyridine thiosemicarbazone for 30 min 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 C 18 column chromatography. A specific activity of about 370–740 MBq/mmol (10–20 Ci/mmol) was obtained. The stability of the final product was checked in the absence and presence of human serum at 37 °C for up to 3 h. The partition coefficient of the final complex was also determined.