Effect of lipophilicity on biological properties of109Pd-porphyrin complexes: a preliminary investigation

Abstract

The present study is designed to investigate the effect of lipophilicity of109Pd-porphyrin complexes on their biological properties which were evaluated in tumor-bearing animal model. The insight obtained could be utilized to develop other radiometalated porphyrin complexes with optimum tumor uptake and tumor to background ratio as potential agents for targeted tumor therapy.109Pd was produced by thermal neutron bombardment on enriched (in109Pd) metallic palladium target at a flux of 3 × 1013n/cm2.s for 3 d.109Pd complexes of three different porphyrin derivatives, namely, 5,10,15,20-tetrakis[3,4- bis(carboxymethyleneoxy)phenyl]porphyrin(I), 5,10,15,20-tetrakis[3,4-bis(carboethoxymethyleneoxy)phenyl]porphyrin(II) and 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin(III), which differ in their peripheral substituents, were synthesized. The biological behavior of the complexes was studied in Swiss mice bearing fibrosarcoma tumors.109Pd was produced with a specific activity of ~1.85 GBq/mg (50 mCi/mg) and radionuclidic purity of 100%. All the109Pd complexes were obtained in high yield (>97%) and they exhibited satisfactory in vitro stability at room temperature. The lipophilicity of the complexes follows the order109Pd-II ≫109Pd-III >109Pd-I. Biodistribution studies revealed that the most lipophilic109Pd-II complex exhibited highest initial tumor uptake but poor tumor/liver ratio, while109Pd-III complex exhibited the best tumor/liver ratio with reasonably good tumor accumulation. The lipophilicity of109Pd-porphyrin complexes was found to have considerable effect on their biological characteristics and radiometal-porphyrin complexes with optimum tumor uptake and adequately high tumor to background ratio could be synthesized by optimization of the lipophilicity through proper selection of peripheral substituents.