15 research outputs found
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BPA uptake in rat tissues after partial hepatectomy
In boron neutron capture therapy (BNCT), boron given as boronophenylalanine (BPA) accumulates transiently not only in tumors but also in normal tissues. Average boron concentrations in transplanted 9L gliosarcoma tumors of 20 rats were 2.5 to 3.7 times concentrations found in blood. Although boron levels in a variety of tissues were also higher than blood the concentrations were less than the lowest found in the tumor. Further note than although BPA is a structural analogue of phenylalanine (Phe), the pathway of BPA uptake into regenerating liver may not be linked to Phe uptake mechanisms
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Uptake of [sup 10]B in gliosarcomas following the injection of gluthathione monoethyl ester and sulfhydryl borane
The sulfhydryl borane Na[sub 2][sup 10]B[sub 12]H[sub 11]SH (BSH) was developed as a capture agent for BNCT about 20 years ago and is the compound currently used clinically in Japan for BNCT of malignant brain tumors. Tumor [sup 10]B concentrations following the infusion of the oxidized BSH, a disulfide dimer (Na[sub 4][sup 10]B[sub 24]H[sub 22]S[sub 2]), are nearly twice those obtained following administration of equal amounts of boron as BSH. Also, the rate of decrease of tumor [sup 10]B concentration is slower after dimer infusion than after BSH infusion. When BNCT was administered to rats bearing intracerebral gliosarcomas, the animals infused with dimer had a significant longer median survival time. Dimer, on the other hand, induces a moderately severe, but reversible, hepatotoxicity which may complicate its use in humans. Intracellular glutathione plays an important role in defense against radical-mediated tissue injury. Glutathione monoesters have been reported to have a protective effective on cisplatin toxicity and on radical-induced acute pancreatitis. We investigated the possibility of reducing dimer-induced hepatotoxicity by pre-administration of GSH-ME. The results indicate that not only does the pre-administration of GSH-ME markedly reduce dimer-induced hepatotoxicity, but also results in nearly a doubling of tumor boron concentration. Furthermore, GSH-ME markedly increases tumor boron uptake and retention following administration of BSH
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Might iodomethyl-{alpha}-tyrosine be a surrogate for BPA in BNCT?
A single-photon emission computed tomography [SPECT] imaging agent that is an analogue of a boron carrier for boron neutron-capture therapy [BNCT] of cerebral gliomas would be useful for assessing the kinetics of boron uptake in tumors and in the surrounding brain tissues noninvasively. BNCT is based on the interaction of thermalized neutrons with {sup 10}B nuclei in the targeted tumor. For BNCT of brain tumors, it is crucial that {sup 10}B concentrations in radiosensitive regions of the brain be minimal since malignant cells and vital brain tissues are often inter-mingled at the margins of the tumor. Currently, boronophenylalanine [BPA]-mediated BNCT is undergoing preliminary clinical study for postoperative radiotherapy of glioblastorna multiforme at Brookhaven National Laboratory. Investigators in Japan are developing {sup 18}F-fluoroboronophenylaianine [FBPA] as a positron {sup 18}F (T{sub 1/2} = 110 min), which is usually emission tomography [PET] surrogate for BPA. generated at a cyclotron dedicated to PET, is generally a minimally perturbing substitute for the 2-H on the aromatic ring because of its small size and the strong covalent bond it forms with carbon. However, SPECT has potential advantages over PET: (1) SPECT is clinically more widely available at lower cost; (2) most radioisotopes for the synthesis of SPECT agents can be purchased; (3) SPECT is less difficult to implement. It is thought that the quality of images derived from the two techniques would each be sufficiently informative for BNCT treatment planning purposes, provided that the SPECT and PET agents being considered were both pharmacokinetic surrogates for BPA. This study evaluated the use of {sup 123}I alpha methyltyrosine as a surrogate for BPA in BNCT
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Major compound-dependent variations of sup 10 B(n. alpha. ) sup 7 Li RBE for the 9L RAT gliosarcoma in vitro and in vivo
Relative biological effectiveness (RBE) values for the high linear-energy-transfer (LET) radiations produced during born neutron capture therapy (BNCT) were determined using the 9L rat gliosarcorna both in vitro and as an intracerebral tumor. In the absence of {sup 10}B, the combined effect of the recoiling protons from the {sup 14}N(n,p){sup 14}C and the {sup 1}H(n,n{prime})p reactions, compared to an iso-effect endpoint produced by 250 kVp x-rays, yielded RBEs for these high-LET protons of 4.4 in vitro and 3.8 in an in vivo/in vitro assay. RBEs for the {sup 10}B(n,{alpha}){sup 7}Li reaction were calculated from cell survival data following reactor irradiation in the presence or in the absence of the either of the amino acid, p-boronophenylalanine (BPA) or the sulfhydryl dodecaborane dimer (BSSB). With BPA, RBE values ranged from 3.5 to 11.4, while under the same set of conditions with BSSB, RBE values ranged from 1.1 to 4.3. In vitro, higher RBEs for the {sup 10}B(n,{alpha}){sup 7}Li reaction using BPA than with BSSB suggest a difference in distribution of {sup 10}B relative to the nucleus
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Spatially fractionated microirradiation of normal CNS and gliosarcomas of the rat with synchrotron photons: Cell and tissue lesions; Raeumlich fraktionierte Mikrobestrahlung von normalem ZNS und Gliosarkomen der Ratte mit Synchrotron-Photonen: Zell- und Gewebelaesionen
Rats were implanted intracerebrally with 9L gliosarcoma cells were used to experimentally determine the curative effectiveness of synchrotron radiation produced by the National Synchrotron Radiation Source. Radiation was delivered in beams with each ray 25 micrometers thick and arranged in an array of 4 mm corners. All experimental animals receiving the gliosarcoma cells and not treated died within four weeks. Treated animals surviving 113 days were sacrificed and their brains were examined histologically