A novel boronated-porphyrin as a radio-sensitizing agent for boron neutron capture therapy of tumours: in vitro and in vivo studies.
A water-soluble [meso-tetra(4-nido-carboranylphenyl)porphyrin] (H(2)TCP) bearing 36 boron atoms was studied for its accumulation and its radio/photo-sensitization efficiency towards murine melanotic melanoma cells. The amount of H(2)TCP in the cells increased with the porphyrin dose in the incubation medium up to 100 microM 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 H(2)TCP intratumorally (1 mg/kg) and intravenously (10 mg/kg). At 0.5h after i.t. administration or at 24 h after i.v. injection, the amounts of (10)B in the tumour were about 60 ppm and about 6 ppm, respectively. The distribution of H(2)TCP 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 of (10)B 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 H(2)TCP-BNCT was compared with that obtained by irradiation after intraperitoneal injection of boron-phenylalanine.
Jori
G
G
Department of Biology, University of Padova, Via U. Bassi 58/B, 35121 Padova, Italy. jori@bio.unipd.it
Soncin
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Friso
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Vicente
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MG
Hao
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Miotto
G
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Colautti
P
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Moro
D
D
Esposito
J
J
Rosi
G
G
Nava
E
E
Sotti
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G
Fabris
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D000818:Animals; D001896:Boron Compounds / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002470:Cell Survival / Q000528:radiation effects; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011166:Porphyrins / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D001896:Boron Compounds; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C527224:meso-tetra(4-nido-carboranylphenyl)porphyrin