Development of [103Pd]-2-acetylpyridine 4N-methyl thiosemicarbazone complex for targeted therapy

Abstract

Due to interesting biological properties of palladium-thiosemicarbazono complexes, production of a 103Pd-labeled anti-cancer complex, i.e., [103Pd]-2-acetylpyridine 4N-methylthiosemicarbazone ([103Pd]-APMTS) was developed. Palladium-103 (T1/2 = 16.96 d) produced via the 103Rh(p,n)103Pd nuclear reaction using natural rhodium target, was separated from the irradiated target material. Proton energy was 18 MeV with 200 mA irradiation for 15 hours (final activity 700 mCi of 103Pd2+, RCY>95%, radionuclidic purity>99%). The final activity was eluted in form of Pd(NH3)2Cl2 in order to react with 2-acetylpyridine-4N-methylthiosemicarbazone to yield [103Pd]-APMTS. Chemical purity of the final product was confirmed to be within the accepted limits by polarography. [103Pd]-APMTS was prepared with a radiochemical yield of more than 80% at room temperature after 3 hours. The labeling reaction was optimized for time, temperature and radioactivity and ligand ratio. A mixture of APMTS and Pd activity in ethanol was heated at 90 °C for 3 hours followed by reverse phase SPE purification using C18 plus Sep-Pak. Radiochemical purity of more than 99% using RTLC and specific activity of about 12500 Ci/mol was obtained. The stability of the tracer was checked in the final product and the presence of human serum at 37 °C up to 3 hours. The partition coefficient of the final complex was determined by octanol : saline buffer distribution.