Evaluation of carborane-containing porphyrins as tumour targeting agents for boron neutron capture therapy
| Autor: | Michiko Miura, P L Micca, C D Fisher, Daniel N. Slatkin, John C. Heinrichs, C R Gordon |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
inorganic chemicals
Boron Compounds Porphyrins chemistry.chemical_element Boron Neutron Capture Therapy Pharmacology chemistry.chemical_compound Mice Pharmacokinetics In vivo Weight Loss Animals Radiology Nuclear Medicine and imaging Chelation Boron Heme Mice Inbred BALB C Dose-Response Relationship Drug Molecular Structure business.industry Mammary Neoplasms Experimental General Medicine Porphyrin Dose–response relationship chemistry Carborane Female Nuclear medicine business Neoplasm Transplantation |
| Zdroj: | The British journal of radiology. 71(847) |
| ISSN: | 0007-1285 |
| Popis: | A number of carborane-containing porphyrins were administered to mice bearing subcutaneously transplanted mammary carcinomas. Administration was via serial intraperitoneal (i.p.) injections to assess their relative toxicities and tumour affinities. Three analogues of the natural porphyrin heme and four tetraphenylporphyrins (TPPs) were given at total doses of 78-245 micrograms g-1 body weight. The water-insoluble TPPs were less toxic to mice, and delivered greater amounts of boron to tumour than did the water-soluble TPPS and the heme analogues. One such compound, NiTCP-H, delivered more than 100 micrograms B g-1 to tumour tissue with a tumour:blood boron concentration ratio greater than 500:1 and a tumour: brain boron concentration ratio greater than 50:1, 4 days after the last of six i.p. injections given over 2 days. Another TPP analogue, NiTCP, delivered approximately 50 micrograms B g-1 to tumour with similar boron concentrations in normal tissues. Neither compound was toxic to mice at total doses of approximately 200 micrograms g-1 body weight. In contrast, the heme analogues were toxic and, with the exception of VCDP, delivered less boron to tumour than NiTCP and NiTCP-H. The two porphyrins with the greatest potential for application to boron neutron capture therapy (BNCT), NiTCP and NiTCP-H, yielded higher tumour:blood and tumour:brain boron concentration ratios in mice than could be achieved with p-boronophenylalanine (BPA) and sodium mercaptoundecahydrododecaborate (BSH), the compounds which are currently being used in clinical trials of BNCT in the treatment of glioblastoma. The boron delivered by each of the porphyrins tested remained in tumour tissue longer than did boron delivered by either BPA or BSH. The copper and nickel chelates of these porphyrins behave identically in vivo. The former offer the potential for imaging by 67Cu-mediated single photon emission computed tomography (SPECT) to aid BNCT treatment planning. |
| Databáze: | OpenAIRE |
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