Carborane-containing metalloporphyrins for BNCT

Conference · Tue Dec 31 04:00:00 EST 1996

OSTI ID:475594

Miura, Michiko; Joel, D D; Nawrocky, M M; Micca, P L ^[1]

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1. and others

For BNCT of malignant brain tumors, it is crucial that there be relatively high boron concentrations in tumor compared with normal tissues within the neutron-irradiated treatment volume. Fairchild and Bond estimated that major advances in BNCT should be possible if ratios of {sup 10}B concentrations in tumor to those in normal tissue (e.g. brain and blood) were at least 5: 1. Given that the only current boron carrier being tested clinically in the U.S., p-boronophenyl-alanine[BPA], yields tumor blood and tumor brain ratios of about 3:1, the criteria for new boronated compounds should be to at least match these ratios and maintain tumor boron concentrations greater than 30 {mu}g B/g. Although previously tested boronated porphyrins have not only matched but surpassed these ratios, it was at a cost of greater toxicity. Chemical and hematological assays of blood analytes; showed marked thrombocytopenia, a decrease to about one-tenth the normal concentration of platelets circulating in the blood, in addition to abnormalities in concentrations of circulating enzymes, that indicated liver toxicity. The physical appearance and behavior of the affected mice were different from those of mice injected with solvent only. Although thrombocytopenia and other toxic effects had disappeared after a few days, previously tested porphyrins would not be safe to infuse into patients for BNCT of potentially hemorrhagic malignant tumors in the brain such as glioblastoma multiforme and metastatic melanoma. We synthesized a different boronated porphyrin, tetracarboranylphenylporphyrin, [TCP] and inserted nickel, copper, or manganese into its coordination center. Biological studies of NiTCP in mice and of CuTCP in rats show that these compounds elicit little or no toxicity when given at potentially therapeutic doses.

• Research Organization: Brookhaven National Lab., Upton, NY (United States)
• Sponsoring Organization: USDOE Office of Energy Research, Washington, DC (United States)
• DOE Contract Number: AC02-76CH00016
• OSTI ID: 475594
• Report Number(s): BNL--64237; CONF-9609293--10; ON: DE97006096
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BORON 10
BRAIN
CARBORANES
COPPER COMPLEXES
COST
MANGANESE COMPLEXES
NEUTRON CAPTURE THERAPY
NICKEL COMPLEXES
ORGANIC BORON COMPOUNDS
PATIENTS
PORPHYRINS
TOXICITY