Boron neutron capture therapy of malignant melanoma of the iris or choroid has the potential to 1) selectively treat melanoma with the use of boronated melanoma seeking compounds - such as p-boronophenylalanine (BPA), 2) use a form of radiation that does not require surgical manipulation of the eye, and 3) spare normal ocular structures from radiation damage. We have demonstrated in preliminary experiments that BPA yields adequate uptake of boron within the melanoma (>15 ug B/g tumor) to allow for irradiation with slow neutrons producing total radiation dose an dose rate sufficient to sterilize melanoma. Also our data shows significant improvement in tumor to blood ratios of boron with BPA when compared to sodium pentaborate which was used previously in the treatment of rabbit eye tumors, and also when compared to Na2B12H11SH(BSH) currently being used in Japan to treat brain tumors. BPA is currently being used clinically to treat subcutaneous melanomas in Japan. The use of the Greene melanoma model in the rabbit will enable experiments to define many of the parameters needed to initiate clinical trials. The biodistribution data with BPA will determine the optimum treatment time and thus allow for proper irradiation with slow neutrons. Both a thermal neutron beam and a newly installed and optimized epithermal neutron beam are now available at the Brookhaven Medical Research Reactor for these studies. In addition, histopathological evaluation of eyes with iris or choroidal melanoma will allow demonstration of radiation effects on the tumor and on normal ocular structures. This information along with radiation dosimetry and phase I clinical studies of the biodistribution of BPA in humans will lead to clinical therapy trials with BNCT.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008560-02
Application #
3265926
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1990-04-01
Project End
1993-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
North Shore University Hospital
Department
Type
DUNS #
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Packer, S; Coderre, J; Saraf, S et al. (1992) Boron neutron capture therapy of anterior chamber melanoma with p-boronophenylalanine. Invest Ophthalmol Vis Sci 33:395-403
Coderre, J A; Glass, J D; Packer, S et al. (1990) Experimental boron neutron capture therapy for melanoma: systemic delivery of boron to melanotic and amelanotic melanoma. Pigment Cell Res 3:310-8