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Neutron irradiation of human melanoma cells
(Alan R. Liss, Inc, 1989) Brown, K; Mountford, MH; Allen, BJ; Mishima, M; Ichihashi, M; Parsons, P
The biological characteristics and in vitro radiosensitivity of melanoma cells to thermal neutrons were investigated as a guide to the effectiveness of boron neutron capture therapy. Plateau phase cultures of three human malignant melanoma-established cell lines were examined for cell density at confluence, doubling time, cell cycle parameters, chromosome constitution, and melanin content. Cell survival dose-response curves, for cells preincubated in the presence or absence of p-boronophenylalanine. HCl (10B1-BPA), were measured over the dose range 0.6-8.0 Gy (N + gamma). The neutron fluence rate was 2.6 x 10(9) n/cm2/s and the total dose rate 3.7 Gy/h (31% gamma). Considerable differences were observed in the morphology and cellular properties of the cell lines. Two cell lines (96E and 96L) were amelanotic, and one was melanotic (418). An enhanced killing for neutron irradiation was found only for the melanotic cells after 20 h preincubation with 10 micrograms/ml 10B1-BPA. In view of the doubling times of the cell lines of about 23 h (96E and 96L) or of 36 h (418), it seems likely that an increased boron uptake, and hence increased radiosensitivity, might result if the preincubation period with 10B1-BPA is extended to several hours longer than the respective cell cycle times. © Alan R. Liss Inc.
Neutron capture therapy research in Australia
(Alan R. Liss, Inc, 1989) Allen. BJ
Neutron capture therapy research in Australia has continued to grow since the first Australia-Japan workshop in April, 1986. The support base has broadened and the wide range of contributing laboratories includes universities, research institutes, and hospitals. Considerable progress has been made in boron chemistry--an accurate boron assay technique has been developed, boron analogues of chlorpromazine and thiouracil have been synthesised or nearly so, and decaborane conjugation with monoclonal antibodies has been achieved to the required loadings. In vitro cell survival experiments are proceeding in the Moata reactor using human melanoma and mouse cell lines incubated with enriched boronophenylalanine and boron tetraphenyl porphyrins. Electron microscopy examination of radiation damaged morphology shows considerable differences between cell lines. Progress with the nude mouse human melanoma model has been slow because of the lack of a reliable in vivo melanotic melanoma line, and the B16 mouse line is found to be more efficacious. Tailored beam calculations for the 10 MW HIFAR reactor indicate the difficulty of obtaining a suitable therapeutic beam because of the generated gamma dose in the beam filters. A new approach to NCT utilises the enormous cross section of 157Gd and the induced-Auger effect which has been shown to cause double strand breaks in circular DNA. © Alan R. Liss Inc.
Recommendations to the Japanese and Australian Governments for future research and development of melanoma neutron capture therapy
(Alan R. Liss, Inc, 1989) Mishima, Y; Allen, BJ
The paper outlines recommendations for the Japanese and Australian governments to advance research and development in Neutron Capture Therapy (NCT) for malignant melanoma. It highlights successful initial clinical trials utilizing boron compounds, especially 'OB-boronophenylalanine (OB-BPA), and suggests expanding collaborative experiments, enhancing clinical trials, refining therapeutic protocols, and exploring innovative compounds. The potential for improved treatment efficacy with minimal side effects positions NCT as a promising avenue in melanoma therapy. © Alan R. Liss Inc.
Determination of the concentration of complex boronated compounds in biological tissues by inductively coupled plasma atomic emission spectrometry
(Alan R. Liss, Inc, 1989) Tamat, SR; Moore, DE; Allen. BJ
The application of inductively coupled plasma atomic emission spectrometry (ICP-AES) to the determination of the concentration of complex boron-containing compounds in biological tissue samples is described. Tissue digestion is achieved with perchloric acid and hydrogen peroxide in 1 hr at 75 degree C. The ICP-AES method gave a linear response for elemental boron concentration in the range 0.05 to 100 ppm and does not require the reduction of the boron to a simple species, such as boric acid. Complete recovery of boron in complex boron cluster compounds was obtained. The procedure has been applied to the determination of the boron content in compounds synthesised for neutron capture therapy and is suitable for use in biodistribution studies of such compounds, © Alan R. Liss Inc.
Morphological changes in human melanoma cells following irradiation with thermal neutrons
(Alan R. Liss, Inc, 1989) Barkala, DK; Allen, BJ; Brown, JK; Mountford, M; Mishima, Y; Ichihashi, M
Morphological changes in two human melanoma cell lines, MM96 and MM418, following irradiation with thermal neutrons, were studied using light and electron microscopy. The results show that the response of human malignant melanoma cells to neutron irradiation is both cell line dependent and dose dependent, and that in any given cell line, some cells are more resistant to irradiation than others, thus demonstrating heterogeneity in respect to radiosensitivity. Cells repopulating MM96 flasks after irradiation were morphologically similar to the cells of origin whereas in MM418 flasks cells differentiated into five morphologically distinct subgroups and showed increased melanization. The results also show that radiation causes distinctive morphological patterns of damage although ultrastructural changes unique to the high LET particles released from boron 10 neutron capture are yet to be identified. © Alan R. Liss Inc.

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