Tumor-localizing and radiosensitizing properties of meso-tetra(4-nido-carboranylphenyl)porphyrin (H2TCP)

Background and Purpose: Boron Neutron Capture Therapy (BNCT) is a binary cancer treatment that exploits the short range particles released from a nuclear fission reaction involving the non-radioactive B-10 nucleus and low-energy neutrons for the destruction of tumor cells. In this perspective, porphyrins and phthalocyanines can represent a vehicle for the transport of significant amounts of boron to the neoplastic lesion. Material and Methods: B 16F1 melanotic melanoma subcutaneously transplanted in C57/BL6 mice has been used as an in vivo model. Pharmacokinetic studies were performed by intratumoral and intravenous injection of a meso-substituted porphyrin containing 36 B atoms per molecule (H2TCP) and the distribution of H2TCP in the tumor was assessed by fluorescence microscopy analysis. The tumor-bearing mice were exposed to the radiation field for 20 min at a reactor power of 5 kW. Results: At 0.5 h after intratumoral administration or at 24 h after intravenous injection, the amount of B-10 in the tumor was found to be about 60 ppm and about 6 ppm, respectively. In spite of the different amounts of 1013 in the tumor at the time of irradiation, a very similar delay in tumor growth (5-6 days) was induced by neutron irradiation in the two groups of injected mice with respect to control mice. Conclusions: Our results demonstrate that a suitable boron-loaded porphyrin displays a significant affinity for subcutaneous tumors, and upon activation by thermal neutrons, can promote an important response even in a fairly aggressive and generally radioresistant tumor such as melanotic melanoma. Copyright (c) 2008 Society of Porphyrins & Phthalocyanines.