109Pd labeled 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin: a Potential Agent for Targeted Tumor Therapy

Tapas      Das; Sudipta      Chakraborty; H.      D. Sarma; Sharmila      Banerjee

doi:10.2174/1874471011205040340

Abstract

Aim: Radiolabeled porphyrin derivatives could be envisaged as potential agents for targeted tumor therapy owing to the inherent tumor accumulation property exhibited by porphyrins. However, to achieve adequately high tumor accumulation and retention therein along with fast clearance from all non-target organs, an optimum balance between the hydrophilicity and lipophilicity must be achieved. Based on our prior experiences of working with 109Pd-labeled porphyrins with variable lipophilicity and hydrophilicity, we have envisioned a suitable porphyrin derivative which could be expected to have the required balance between lipophilicity and hydrophilicity when complexed with 109Pd. Towards this, 5,10,15,20- tetrakis[4-carboxymethyleneoxyphenyl]porphyrin (PHBEPH) was synthesized, radiolabeled with 109Pd and its biological behavior in small animal model was studied.

Experimental: The porphyrin derivative was synthesized and characterized following the reported procedure and radiolabeled with 109Pd [E β(max) = 1.12 MeV, E γ = 88 keV (3.6%), T1/2 = 13.7 h], which was produced by the thermal neutron bombardment on enriched (98% in 108Pd) metallic Pd target at a flux of 3×1013 n/cm2.s for 3 d. Biological behavior of the radiolabeled agent was studied by biodistribution studies in Swiss mice bearing fibrosarcoma tumors.

Results: 109Pd was produced with a specific activity of ~1.85 GBq/mg (50 mCi/mg) and radionuclidic purity of 100%. 109Pd complex of the synthesized porphyrin derivative was prepared with excellent radiochemical purity (>98%) and the complex was observed to exhibit Log P value of -1.29. Biodistribution studies revealed good tumor uptake [(3.55±0.49)% injected activity (IA)/g] within 30 min post-injection (p.i.) and retention therein till 24 h [(2.56±0.25)% IA)/g], upto which the study was continued. The complex exhibited fast clearance from the non-target organs with favorable tumor/blood and tumor/muscle ratios [(5.09±0.18)% and (284.44±3.25)% at 24 h p.i.].

Conclusion: The complex exhibited good uptake and retention in the tumor along with encouraging target to non-target ratio. Preliminary biological studies indicated the promising attributes of the agent towards its use for targeted radiotherapy.

Keywords: Hydrophilicity, Lipophilicity, 109Pd, Porphyrin, Targeted tumor therapy.

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