Development of [103Pd]-labeled-bis(N 4-methylthiosemicarbazone) complexes as possible therapeutic agents

Abstract

Due to interesting tumor seeking properties of bis-thiosemicarbazones, two radio palladium- bis -thiosemicarbazone complexes, i.e., [103Pd]-pyruvaldehyde- bis(N 4-methylthiosemicarbazone) ([103Pd] PTSM) and [103Pd]- di-acetyl-bis (N 4-methylthiosemicarbazone) ([103Pd]ATSM) were prepared according to the analogy of radio copper homologs. Palladium-103 (t 1/2=16.96 d) was produced via the 103Rh(p,n) 103Pd nuclear reaction with proton energy 18 MeV. The final activity was eluted in form of Pd(NH3)2Cl2 in order to react with bis -thiosemicarbazones to yield [103Pd]-labeled compounds. Chemical purity of the product was confirmed to be below the accepted limits by polarography. [103Pd]-labeled bis -thiosemicarbazones were prepared with a radiochemical yield of more than 80% at room temperature after 60–90 min by vortexing a mixture of thiosemicarbazones and Pd activity in ethanol. The purification of the labeled compounds performed by reverse phase column chromatography using C18 plus Sep-Pak. Radiochemical purity of more than 99% specific activity of about 12500–13000 Ci/mol was obtained. The stability of the complexes was checked in final product and presence of human serum at 37 °C up to 48 h. The partition co-efficients of the final complexes were determined. The initial physico-chemical properties of the labeled compounds were compared to those of their copper homologues.