Uptake of a nido-carboranylporphyrin by human glioma xenografts in athymic nude mice and by syngeneic ovarian carcinomas in immunocompetent mice

Journal Article · Sat Sep 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.18.7265· OSTI ID:5391249

Kahl, S B ^[1]; Joel, D D; Nawrocky, M M; Micca, P L; Tran, K P; Finkel, G C; Slatkin, D N ^[2]

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1. Univ. of California, San Francisco (USA)
2. Brookhaven National Lab., Upton, NY (USA)

A tetraphenylporphyrin bearing four dicarbollide ((B{sub 9}C{sub 2}H{sub 11}){sup {minus}}) cages linked to the o-phenyl ring positions by anilide bonds, known as boronated tetraphenylporphyrin (BTPP), has been synthesized in excellent yield from tetra-(o-aminophenyl)porphyrin and carborane carbonyl chloride followed by base-assisted cage opening and ion exchange to give the highly water-soluble potassium salt. Preliminary studies showed that BTPP accumulates in liver and in a syngeneic ovarian carcinoma, but not in normal brain parenchyma, of mice infused with BTPP subcutaneously for 6 or 7 days via surgically implanted osmotic minipumps. In this study, the uptake of boron was measured in human gliomas xenografted subcutaneously to athymic nude mice in which BTPP was infused intraperitoneally or subcutaneously or both for 3 or 7 days by using similar minipumps. Immunocompetent mice bearing a syngeneic ovarian carcinoma were similarly infused to provide comparative data. Bulk concentrations of boron up to 18 {mu}g/g of glioma and up to 45 {mu}g/g of carcinoma were observed when up to 102 {mu}g/g of tissue was present in the liver after 7 days of BTPP infusion. Glioma boron concentrations were increased by {approx}80% on the average correspondingly greater amounts of BTPP were infused in only 3 days. Cell counts and chemical tests on blood samples from individual mice indicate that BTPP causes moderate hepatotoxicity and thromboxytopenia. This hepatohematic toxicity syndrome should be taken into account if BTPP or a similar agent is used for boron neutron-capture therapy (BNCT) of human malignancies.

• DOE Contract Number: AC02-76CH00016
• OSTI ID: 5391249
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 87:18; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
GLIOMAS
NEUTRON CAPTURE THERAPY
ORGANIC BORON COMPOUNDS
UPTAKE
PORPHYRINS
BORON 10
BRAIN
CARCINOMAS
CYTOLOGY
LIVER
MAN
MICE
NEUTRON SPECTROSCOPY
ANIMALS
BIOLOGY
BODY
BORON COMPOUNDS
BORON ISOTOPES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
DIGESTIVE SYSTEM
DISEASES
GLANDS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MEDICINE
NEOPLASMS
NERVOUS SYSTEM
NEUTRON THERAPY
NUCLEAR MEDICINE
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PRIMATES
RADIOLOGY
RADIOTHERAPY
RODENTS
SPECTROSCOPY
STABLE ISOTOPES
THERAPY
VERTEBRATES
550604* - Medicine- Unsealed Radionuclides in Therapy- (1980-)