Experimental boron neutron capture therapy for melanoma: systemic delivery of boron to melanotic and amelanotic melanoma.
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.
Coderre
J A
JA
Medical Department, Brookhaven National Laboratory, Upton, NY 11973.
Glass
J D
JD
Packer
S
S
Micca
P
P
Greenberg
D
D
D000818:Animals; D001895:Boron / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005134:Eye Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D007554:Isotopes; D008175:Lung Neoplasms / Q000378:metabolism / Q000532:radiotherapy / Q000556:secondary; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009502:Neutrons / Q000627:therapeutic use; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
D001896:Boron Compounds; D007554:Isotopes; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; D001895:Boron; C033685:4-boronophenylalanine