Radiosynthesis and bioevaluation of [68Ga]-labeled 5,10,15,20-tetra(4-methylpyridyl)-porphyrin for possible application as a PET radiotracer for tumor imaging.

Abstract

Porphyrins have inherent ability to localize preferentially in tumor lesions. Cationic porphyrins are readily water soluble and reported to exhibit strong DNA-binding capabilities. Therefore, attempt has been made to prepare a water soluble [(68)Ga]-labeled cationic porphyrin, viz., 5,10,15,20-tetra(4-methylpyridyl)porphyrin (TMP), and evaluate its potential as a positron emission tomography (PET) radiotracer for tumor imaging. The cationic porphyrin TMP was synthesized following a two-step procedure and subsequently radiolabeled with Ga-68, eluted from a commercial (68)Ge/(68)Ga generator. Purification of the [(68)Ga]-labeled porphyrin derivative was carried out using Sep-Pak(®) cartridges. The tumor-targeting potential of the [(68)Ga]-labeled-5,10,15,20-tetra(4-methylpyridyl)porphyrin was evaluated by biodistribution studies in Swiss mice bearing fibrosarcoma tumor. Under optimized reaction conditions, [(68)Ga]-labeled TMP was obtained with ~90% radiochemical purity which was subsequently improved to >99% after purification through Sep-Pak(®) cartridges. Biodistribution studies revealed high tumor uptake of the radiotracer within 30-min post-injection (6.47 ± 0.87% of injected activity) and retention until the final 2 h post-administration (4.48 ± 1.11% of injected activity) time point. The initial uptake observed in non-target organs cleared away with time resulting in gradually improving tumor/blood and tumor/muscle ratios. Preliminary bioevaluation studies indicated the potential of the radiolabeled porphyrin derivative for tumor imaging, and further detailed studies are warranted to evaluate the true potential of the developed radiotracer.