Treatment of Malignant Melanoma by Single Thermal Neutron Capture Therapy With Melanoma-Seeking 10b-Compound

Mishima, Yutaka; Honda, C.; Ichihashi, Masamitsu; Obara, Hidefumi; Hoshino, Junichi; Fukuda, Hiroshi; Karashima, Hiroshi; Kobayashi, Tooru; Kanda, Keiji; Yoshino, Kazuo

doi:10.1016/s0140-6736(89)90567-9

Cited by 330 publications

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“…The peak of this thermalization of epithermal neutrons is about 3 cm in depth. The heavy water facility at Kyoto University Reactor (KUR) was remodeled in 1996 for production of an epithermal neutron beam.2) We expected that the aforesaid problem (poor penetration with a thermal neutron beam) might be overcome and it might become feasible to apply BNCT to malignant hepatic tumors.We examined the effects of BNCT on experimental liver tumors and normal hepatocytes by using two boron compounds which are being used in clinical BNCT trials for malignant glioma and malignant melanoma, [3][4][5] to explore the feasibility of BNCT treatment of liver tumors. …”

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The Effects of Boron Neutron Capture Therapy on Liver Tumors and Normal Hepatocytes in Mice

Suzuki

Masunaga

Kinashi

et al. 2000

Japanese Journal of Cancer Research

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To explore the feasibility of employing boron neutron capture therapy (BNCT) to treat liver tumors, the effects of BNCT were investigated by using liver tumor models and normal hepatocytes in mice. Liver tumor models in C3H mice were developed by intrasplenic injection of SCCVII tumor cells. After borocaptate sodium (BSH) and boronophenylalanine (BPA) administration, 10 B concentrations were measured in tumors and liver and the liver was irradiated with thermal neutrons. The effects of BNCT on the tumor and normal hepatocytes were studied by using colony formation assay and micronucleus assay, respectively. To compare the effects of BSH-BNCT and BPA-BNCT, the compound biological effectiveness (CBE) factor was determined. The CBE factors for BSH on the tumor were 4.22 and 2.29 using D 10 and D 0 as endpoints, respectively. Those for BPA were 9.94 and 5.64. In the case of hepatocytes, the CBE factors for BSH and BPA were 0.94 and 4.25, respectively. Tumor-to-liver ratios of boron concentration following BSH and BPA administration were 0.3 and 2.8, respectively. Considering the accumulation ratios of 10 B, the therapeutic gain factors for BSH and BPA were 0.7-1.3 and 3.8-6.6, respectively. Therefore, it may be feasible to treat liver tumors with BPA-BNCT. Key words: BNCT -BSH -BPA -Liver tumorsVarious therapeutic options have been examined for the treatment of unresectable primary and secondary malignant tumors in the liver. These include percutaneous ethanol injection, intraarterial drug infusion, embolization, intraarterial chemoembolization and radiotherapy. However, the results of these treatments have not been satisfactory. In many cases there are multiple tumors, and the liver cannot tolerate large treatment volumes, especially in radiotherapy. Boron neutron capture therapy (BNCT) which combines an administration of a tumor-seeking boron compound with thermal neutron irradiation might be an effective treatment for malignant hepatic tumors for the following reasons. In the boron neutron capture reaction, 10 B absorbs a thermal neutron and releases two high linear energy transfer (LET) particles, an α particle and a 7 Li nucleus. These particles have path lengths of 9 and 4 µm, respectively, depositing all their energy within a range of about one cell diameter from the capture reaction site. Accordingly these high-LET particles have large relative biological effectiveness (RBE), and effective cell killing can be expected in malignant tumors, which are resistant to conventional radiotherapy using photons or electrons. The path lengths of these particles are so short that if tumor cells accumulate the boron compound selectively, only tumor cells can be killed.A major limitation in the application of BNCT using thermal neutrons is the tumor depth. Deep-seated tumors, such as hepatic tumors, are difficult to treat because of the poor penetration of thermal neutrons, which have energies <0.5 eV and a 15-16 mm half-value layer in water. Epithermal beams, with energies 0.5 eV to 10 keV, have better penetration in tiss...

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“…We examined the effects of BNCT on experimental liver tumors and normal hepatocytes by using two boron compounds which are being used in clinical BNCT trials for malignant glioma and malignant melanoma, [3][4][5] to explore the feasibility of BNCT treatment of liver tumors. was prepared as follows.…”

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The Effects of Boron Neutron Capture Therapy on Liver Tumors and Normal Hepatocytes in Mice

Suzuki

Masunaga

Kinashi

et al. 2000

Japanese Journal of Cancer Research

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“…BPA is expected to be incorporated into tumour cells by specific uptake mechanisms involving LAT-1 [3,4,21,22]. BSH is not actively incorporated into tumour cells, but enters cells by a concentration gradient.…”

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Boron Carbide Particle as a Boron Compound for Boron Neutron Capture Therapy

Iwagami¹,

Ishikawa²,

Koshizaki³

et al. 2014

J Nucl Med Radiat Ther

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“…The boron-containing amino acid analogue, boronophenylalanine (BPA) has been shown to deliver boron selectively to melanoma tissue (Mishima et al, 1989b). BPA has been successful in animal models and has recently been used in Japan in human trials of BNCT for melanoma (Mishima et al, 1989a). In a study of BPA distribution in a rat glioblastoma, Coderre et al (1990Coderre et al ( , 1994) demonstrated a tumour-blood ratio of 4:1 compared with 0.7:1 for BSH.…”

Section: Growth Inhibition Of Tumour Treated With '0b Solutionsmentioning

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Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy

Yanagië

Tomita²,

Kobayashi³

et al. 1997

Br J Cancer

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Histopathologically, hyalinization and necrosis were found in '0B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of '0B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation.

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Treatment of Malignant Melanoma by Single Thermal Neutron Capture Therapy With Melanoma-Seeking 10b-Compound

Cited by 330 publications

References 3 publications

The Effects of Boron Neutron Capture Therapy on Liver Tumors and Normal Hepatocytes in Mice

The Effects of Boron Neutron Capture Therapy on Liver Tumors and Normal Hepatocytes in Mice

Boron Carbide Particle as a Boron Compound for Boron Neutron Capture Therapy

Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy

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