A novel [109Pd] palladium labeled porphyrin for possible use in targeted radiotherapy

Abstract

The preferential accumulation of porphyrins in malignant tumor cells has been adequately documented. Hence, porphyrin derivatives radiolabeled with a suitable therapeutic radionuclide could be envisaged as potential agents for targeted tumor radiotherapy. Working in this direction, we have radiolabeled a porphyrin derivative, namely, 5,10,15,20-tetrakis[3,4-bis(carboethoxymethyleneoxy)phenyl]-porphyrin, synthesized in-house, with 109Pd [E β(max)=1.12 MeV, E γ=88 keV 3.6(%), T 1/2 = 13.7 h]. The envisaged rationale towards designing of this agent is based on the assumption that 109Pd would complex with the tetrapyrrole donor array constituting the porphyrin core, thereby providing a highly stable chelated complex, and the peripheral ester groups would impart optimum lipophilicity needed for sufficiently high tumor accumulation and retention therein. 109Pd was produced with a specific activity of ∼1.85 GBq/mg and radionuclidic purity of 100% by the thermal neutron bombardment of enriched (98% in 108Pd) metallic Pd target at a flux of 3×1013 n/cm2s1 for 3 d. The porphyrin derivative was synthesized by a multi-step reaction and characterized by normal spectroscopic techniques. 109Pd complex of the synthesized porphyrin derivative was prepared with excellent radiochemical purity (>98%) and the complex was observed to be stable upto 24 h at room temperature. Biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumors revealed good tumor uptake [(5.28±1.46)% injected activity (IA)/g] within 30 min post-injection (p.i.). The complex exhibited favorable tumor/blood and tumor/muscle ratios [1.69±0.23 and 5.00±1.54, respectively at 3 h p.i.], albeit with high liver uptake throughout the time of study (>20% IA).