A novel boronated-porphyrin as a radio-sensitizing agent for boron neutron capture therapy of tumours: In vitro and in vivo studies

G Jori, M. Soncin, E. Friso, M.G.H. Vicente, E. Hao, G. Miotto, P. Colautti, D. Moro, J. Esposito, G. Rosi, E. Nava, G. Sotti, C. Fabris

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Abstract

A water-soluble [meso-tetra(4-nido-carboranylphenyl)porphyrin] (H2TCP) bearing 36 boron atoms was studied for its accumulation and its radio/photo-sensitization efficiency towards murine melanotic melanoma cells. The amount of H2TCP in the cells increased with the porphyrin dose in the incubation medium up to 100 μM with no significant dark toxicity. Fluorescence microscopy observations showed that the porphyrin was largely localized intracellularly. Based on these "in vitro" results our investigations were pursued using the B16F1 melanotic melanoma subcutaneously transplanted in C57BL6 mice as "in vivo" model. Phormacokinetic studies were performed by injection of H2TCP intratumorally (1 mg/kg) and intravenously (10 mg/kg). At 0.5 h after i.t. administration or at 24 h after i.v. injection, the amountsof10B in the tumour were about 60 ppm and about 6 ppm, respectively. The distribution of H2TCP in the tumour after intravenous or intratumoural injection was also assessed by fluorescence microscopy analyses. Under these conditions, preliminary BNCT studies were carried out using a new thermal column called HYTOR (HYbrid Thermal spectrum sHifter TapirO Reactor) inserted in the fast nuclear reactor Tapiro at Enea Casaccia, Italy. The mice were exposed to HYTHOR radiation field for 20 min at a reactor power of 5 kW. In spite of different amounts of10B in the tumour at the irradiation time, a similar significant delay in tumour growth (5-6 days) was induced by neutron irradiation in intratoumorally and intravenously injected mice. The response of the melanotic melanoma to H2TCP-BNCT was compared with that obtained by irradiation after intraperitoneal injection of boron-phenylalanine. © 2009 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)-
JournalApplied Radiation and Isotopes
Volume67
Issue number7-8 SUPPL.
DOIs
Publication statusPublished - Jul 2009
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Radiation

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