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 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The boron-containing melanin precursor analogue p-boronophenylalanine (BPA) has previously been shown to selectively deliver boron to pigmented murine melanomas when administered in a single intragastric dose. If boron neutron capture therapy is to become a clinically useful method of radiation therapy for human malignant melanoma, the boron carrier must be capable of delivering useful amounts of boron to remote tumor sites (metastases) and to poorly pigmented melanomas. We have now determined the ability of BPA to accumulate in several nonpigmented melanoma models including human melanoma xenografts in nude mice. The absolute amount of boron in the nonpigmented melanomas was about 50% of that observed in the pigmented counterparts but was still selectively concentrated in the tumor relative to normal tissues in amounts sufficient for effective neutron capture therapy. Single intragastric doses of BPA resulted in selective localization of boron in the amelanotic Greene melanoma carried in the anterior chamber of the rabbit eye and in a pigmented murine melanoma growing in the lungs. The ratio of the boron concentration in these tumors to the boron concentration in the immediately adjacent normal tissue was in the range of 3:1 to 4:1. These distribution studies support the proposal that boron neutron capture therapy may be useful as a regional therapy for malignant melanoma.
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PMID:Experimental boron neutron capture therapy for melanoma: systemic delivery of boron to melanotic and amelanotic melanoma. 210 31

Trimethylamine carboxyboranes including their esters and amides were shown to have antineoplastic activity in vivo against Ehrlich ascites carcinoma growth. The derivatization to the ester or amide did not necessarily improve activity. Cytotoxicity of the derivatives was observed against the growth of murine and human tumor cells. Selectivity was demonstrated by the boron derivatives in the human solid tumor screens. Almost all the compounds demonstrated cytotoxicity against single-cell suspension growths, eg Tmolt3, L1210, HeLa-S3. Selection of two compounds to examine their mode of action in L1210 lymphoid leukemia cells showed that the agents perferentially inhibited DNA synthesis followed by protein and RNA synthesis. The d(TTP) pools were markedly reduced because of inhibition of nucleotide kinase activity. The agents also inhibited regulatory enzymes in the de novo purine pathway and afforded DNA strand scission. These effects by the agents were probably additive to bring about tumor cell death.
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PMID:The antineoplastic activity of trimethylamine carboxyboranes and related esters and amides in murine and human tumor cell lines. 213 Oct 45

Physics studies related to radiation source, spectroscopy, beam quality, dosimetry, and biomedical applications using the Kyoto University Reactor Heavy Water Facility are described. Also, described are a Nickel Mirror Neutron Guide Tube and a Super Mirror Neutron Guide Tube that are used both for the measurement of boron concentration in phantom and living tissue and for precise measurements of neutron flux in phantom in the presence of both light and heavy water. Discussed are: (1) spectrum measurements using the time of flight technique, (2) the elimination of gamma rays and fast neutrons from a thermal neutron irradiation field, (3) neutron collimation without producing secondary gamma rays, (4) precise neutron flux measurements, dose estimation, and the measurement of boron concentration in tumor and its periphery using guide tubes, (5) the dose estimation of boron-10 for the first melanoma patient, and (6) special-purpose biological irradiation equipment. Other related subjects are also described.
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PMID:Biomedical irradiation system for boron neutron capture therapy at the Kyoto University Reactor. 217 58

Neutron therapy has proven to be clinically useful in cases of advanced, slow-growing radioresistant head and neck carcinoma. Therapeutic effects might be based on direct DNA damaging and thus immediate cell-killing, on the generation of free oxygen radicals and, among others, on the fact that heavy particle radiation is said to be less dependent on the presence of oxygen than gamma rays, i.e. on a lower oxygen enhancement ratio (OER). The smaller difference in reaction between oxygenated and nonoxygenated cells could entail advantages as well as disadvantages, depending on the characteristics of the tumor cell population and of the normal tissue. It is therefore essential to select patients and tumours with an expectedly high therapeutic gain factor. Fission neutrons for tumour therapy: As evaluated by several in vitro and in vivo studies (11/13) the biological efficiency (RBE) of the RENT (Reactor Neutron Therapy) beam in Munich seems to be among the highest of all clinically used neutron beams. For a single dose range between 2 and 8 Gy the RBE for chronic radiation damage is relatively small (2). Consequently, patients with recurrent or metastatic carcinomas of the head and neck are treated with a single dose of 200-250 cGy after previous surgery and/or combined radiochemotherapy. The main limitation of fission neutrons is the small penetration depth. Possibilities of clinical implementation of boron neutron capture therapy (BNCT) in otorhinolaryngology: In near surface tumours it is possible to administer high doses of 10boron not selectively, i.e. no selective tumour-seeking compound is needed. Animal experiments with intratumoural injection of 10boron glycine have shown a strong effect on tumour growth delay (18).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Principles of therapy with fission neutrons and boron neutron capture therapy for radioresistant head-neck malignancies]. 222 92

This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity.
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PMID:Inhibition of tumor growth in a glioma model treated with boron neutron capture therapy. 223 30

The efficacy of boron neutron capture therapy (BNCT) for the treatment of intracerebrally implanted rat gliosarcomas was tested. Preferential accumulation of 10B in tumors was achieved by continuous infusion of the sulfhydryl borane dimer, Na4(10)B24H22S2, at a rate of 45-50 micrograms of 10B per g of body weight per day from day 11 to day 14 after tumor initiation (day 0). This infusion schedule resulted in average blood 10B concentrations of 35 micrograms/ml in a group of 12 gliosarcoma-bearing rats and 45 micrograms/ml in a group of 10 similar gliosarcoma-bearing rats treated by BNCT. Estimated tumor 10B levels in these two groups were 26 and 34 micrograms/g, respectively. On day 14, boron-treated and non-boron-treated rats were exposed to 5.0 or 7.5 MW.min of radiation from the Brookhaven Medical Research Reactor that yielded thermal neutron fluences of approximately 2.0 x 10(12) or approximately 3.0 x 10(12) n/cm2, respectively, in the tumors. Untreated rats had a median postinitiation survival time of 21 days. Reactor radiation alone increased median postinitiation survival time to 26 (5.0 MW.min) or 28 (7.5 MW.min) days. The 12 rats that received 5 MW.min of BNCT had a median postinitiation survival time of 60 days. Two of these animals survived greater than 15 months. In the 7.5 MW.min group, the median survival time is not calculable since 6 of the 10 animals remain alive greater than 10 months after BNCT. The estimated radiation doses to tumors in the two BNCT groups were 14.2 and 25.6 Gy equivalents, respectively. Similar gliosarcoma-bearing rats treated with 15.0 or 22.5 Gy of 250-kilovolt peak x-rays had median survival times of only 26 or 31 days, respectively, after tumor initiation.
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PMID:Boron neutron capture therapy of intracerebral rat gliosarcomas. 226 30

NCT is a binary system, in which 10B is physiologically targeted to tumor and then allowed to interact with thermal neutrons generated in the treatment volume by an externally applied neutron beam. Consequently, an unusually large number of parameters are obtained, which bear on the resultant Therapeutic Gain (TG). However, a perusal of these data, as illustrated in Figure 7, indicates that the TG would increase significantly beyond values projected in this paper if the absolute amount of 10B could be increased above 30 ppm. For example, increasing 10B concentration in tumor to 45 ppm would increase TG by approximately 33% (with a T/N of 5). A similar increase in TG would follow an increase in T/N from 5 to 10. Those associated with the development of boron compounds for NCT feel that such developments are within reach.
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PMID:Installation and testing of an optimized epithermal neutron beam at the Brookhaven Medical Research Reactor (BMRR). 226 39

The radiotherapeutic management of primary brain tumors and metastatic melanoma in brain has had disappointing clinical results for many years. Although neutron capture therapy was tried in the United States in the 1950s and 1960s, the results were not as hoped. However, with the newly developed capability to measure boron concentrations in blood and tissue both quickly and accurately, and with the advent of epithermal neutron beams obviating the need for scalp and skull reflection, it should now be possible to mount such a clinical trial of NCT again and avoid serious complications. As a prerequisite, it will be important to demonstrate the differential uptake of boron compound in brain tumor as compared with normal brain and its blood supply. If this can be done, then a trial of boron neutron capture therapy for brain tumors should be feasible. Because boronated phenylalanine has been demonstrated to be preferentially taken up by melanoma cells through the biosynthetic pathway for melanin, there is special interest in a trial of boron neutron capture therapy for metastatic melanoma in brain. Again, the use of an epithermal beam would make this a practical possibility. However, because any epithermal (or thermal) beam must contain a certain contaminating level of gamma rays, and because even a pure neutron beam causes gamma rays to be generated when it interacts with tissue, we think that it is essential to deliver treatments with an epithermal beam for boron neutron capture therapy in fractions in order to minimize the late-effects of low-LET gamma rays in the normal tissue. I look forward to the remainder of this Workshop, which will detail recent progress in the development of epithermal, as well as thermal, beams and new methods for tracking and measuring the uptake of boron in normal and tumor tissues.
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PMID:Clinical considerations for neutron capture therapy of brain tumors. 226 42

The melanin precursor analogue p-boronophenylalanine (BPA) has been used to deliver 10B to melanoma tissue for boron neuron capture therapy. Uptake studies in tumor models other than melanoma now indicate that BPA is capable of delivering therapeutic amounts of boron to tumors other than melanoma. The KHJJ murine mammary tumor carried s.c. in BALB/c mice, the GS-9L rat glioma carried both s.c. and intracranially in F-344 rats, and the human U-87 MG glioma xenograft carried s.c. in nude mice have all shown significant accumulation of boron in tumor tissue following single p.o. (intragastric) doses of BPA. In this KHJJ mammary tumor, the L isomer of BPA was preferentially accumulated compared to the D isomer, indicative of a carrier-mediated transport process. Double-label, whole-body autoradiographic studies in a pigmented murine melanoma have shown that the boron distribution (from BPA) differs from the distribution of a tritiated melanin precursor (tyrosine). Boron accumulated only in the tumor; labeled tyrosine accumulated in tumor, liver, intestinal epithelium, bone-marrow, and secretory glands. Toxicity studies in mice and rabbits indicate that, even at very high doses, BPA p.o. caused no adverse effect in tissues, on blood chemistry, or on differential leukocyte counts. These data indicate that BPA may be generally useful as a boron delivery agent for boron neutron capture therapy of tumors.
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PMID:Selective delivery of boron by the melanin precursor analogue p-boronophenylalanine to tumors other than melanoma. 229 47

The purpose of the present study was to utilize a well-established rat glioma to evaluate boron neutron capture therapy for the treatment of malignant brain tumors. Boron-10 (10B) is a stable isotope which, when irradiated with thermal neutrons, produces a capture reaction yielding high linear energy transfer particles (10B + 1nth----[11B]----4He(alpha) + 7Li + 2.79 MeV). The F98 tumor is an anaplastic glioma of CD Fischer rat origin with an aggressive biological behavior similar to that of human glioblastoma multiforme. F98 cells were implanted intracerebrally into the caudate nuclei of Fischer rats. Seven to 12 days later the boron-10-enriched polyhedral borane, Na2B12H11SH, was administered intravenously at a dose of 50 mg/kg body weight at varying time intervals ranging from 3 to 23.5 hours before neutron irradiation. Pharmacokinetic studies revealed blood 10B values ranging from 0.33 to 10.5 micrograms/ml depending upon the time after administration, a T1/2 of 6.2 hours, normal brain 10B concentrations of 0.5 microgram/g, and tumor values ranging from 1.1 to 12.8 micrograms/g. No therapeutic gain was seen if the capture agent was given at 3 or 6 hours before irradiation with 4 x 10(12) n/cm2 (10 MW-min; 429 cGy). A 13.5-hour preirradiation interval resulted in a mean survival of 37.8 days (P less than 0.01), compared to 30.5 days (P less than 0.03) for irradiated controls and 22.1 days for untreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Boron neutron capture therapy of a rat glioma. 229 79


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