Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, l-boronophenylalanine and boric acid in murine tumors
| Autor: | Adrian C. Begg, R. Huiskamp, R. Verrijk, Vincent Grégoire, Harry Bartelink |
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| Rok vydání: | 1993 |
| Předmět: |
Boron Compounds
Male Radiation-Sensitizing Agents Biodistribution Time Factors Phenylalanine chemistry.chemical_element Boron Neutron Capture Therapy Mice Inbred Strains Borohydrides Kidney Boric acid Mice chemistry.chemical_compound Boric Acids Pharmacokinetics medicine Animals Radiology Nuclear Medicine and imaging Sulfhydryl Compounds Boron Melanoma Mice Inbred C3H Dose-Response Relationship Drug Chemistry business.industry Radiochemistry Brain Hematology medicine.disease Mice Inbred C57BL Neutron capture Liver Oncology Inductively coupled plasma atomic emission spectroscopy Female Sarcoma Experimental Selectivity Nuclear medicine business Injections Intraperitoneal Half-Life |
| Zdroj: | Radiotherapy and Oncology. 27:46-54 |
| ISSN: | 0167-8140 |
| DOI: | 10.1016/0167-8140(93)90043-8 |
| Popis: | Borocaptate sodium (BSH) and l -boronophenylalanine (L-BPA) are two boron carriers used for boron neutron capture therapy (BNCT) in the treatment of glioblastoma and melanoma, respectively. The suitability of these two compounds was evaluated on the basis of pharmacokinetic studies aiming at characterizing their biodistribution, tumor uptake and tumor selectivity. Boric acid was also used as a reference compound since it is nonselective and relatively freely diffusible. The compounds were investigated in two tumor models, a B16 pigmented melanoma and the RIF1 sarcoma. Mice were sacrificed after different boron doses at various post-injection times and tissue and plasma levels measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The proposed minimum effective tumor boron concentration of 15 ppm. was achieved in both tumor models for the three compounds tested, although only for l -BPA in the melanoma was this achieved when tumor-plasma ratios were above 1. In the RIF1 model, maximum tumor concentrations of 44 and 31 ppm B were reached after administration of 50 μg B/g body weight for boric acid and BSH, respectively. After administration of 12.5 μg B/g of l -BPA, maximum concentrations of 15 and 21 ppm were found in the RIF1 and B16 models, respectively. Tumor-plasma ratios (TPR) for BSH remained close to or below unity at all times studied in both tumors. Brain levels of BSH were very low, however, leading to tumor-brain ratios markedly greater than 1 at all times. l -BPA and boric acid showed TPR values above unity in both tumor models, reaching 3.2 in B16. Tissue-plasma ratios after l -BPA reached maxima of 1.3 and 3.1 for brain and muscle, in contrast to the low values for BSH. In conclusion, the study showed only modest selectivity for tumor type for the boron compounds tested, although l -BPA showed significant selectivity for the melanoma and would appear to better than BSH for this tumor type. Although tumor-plasma ratios were lower for BSH than l -BPA, the very low normal brain concentrations with BSH would favor this compound for tumors such as glioblastoma. Data on intracellular distributions, both for tumor and relevant normal tissue subpopulations, will be needed to supplement gross tissue boron data for accurate assessment of potential for BNCT. |
| Databáze: | OpenAIRE |
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