Preparation and preliminary biological evaluation of a novel 109Pd labeled porphyrin derivative for possible use in targeted tumor therapy.

Aim: The labeling of a porphyrin, a tumor-avid agent, with a beta-emitting radionuclide for evaluating its potential as an agent for targeted tumor therapy is reported. A novel water soluble porphyrin viz. 5,10,15,20-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]porphyrin radiolabeled with(109)Pd (E(beta(max))=1.12 MeV, Eg=88 keV (3.6%), T1/2=13.7 h) has been prepared. The designing of this agent is based on the speculation that (109)Pd would complex with the tetrapyrrole donor array constituting the porphyrin core, resulting in a species with peripheral hydrophilic residues for facilitating renal excretion.
Methods: Palladium-109 was produced by thermal neutron bombardment on enriched metallic Pd target at a flux of 3 x 10(13) n/cm(2) x s for 3 days and the porphyrin derivative was synthesized by a multi-step reaction using 3,4 dihydroxybenzaldehyde and pyrrole. The labeling parameters were optimized for obtaining maximum complexation yield and the biological behavior of the radiolabeled porphyrin was studied in Swiss mice bearing fibrosarcoma tumors.
Results: Palladium-109 was produced with a specific activity of approximately 1.85 GBq/mg and approximately 100% radionuclidic purity. Lead-109 complex of the synthesized porphyrin derivative was prepared with excellent radiochemical purity (approximately 98%) and the complex was observed to be stable upto 24 h at room temperature. Results of the biodistribution studies revealed good tumor uptake (2.8+/-0.57%/g) within 30 min post-injection and it remained almost constant till 24 h post-injection. The complex showed predominantly renal clearance (88.68+/-4.01% at 24 h post-injection).
Conclusions: The high tumor/blood and tumor/muscle ratios (4.36 and 38 at 24 h post-injection) exhibited by the radiolabeled porphyrin indicate its potential for using in targeted tumor therapy.