Article Chemistry Small Boron compounds Year 1987

Selective Targeting of Boronophenylalanine to Melanoma in BALB/c Mice for Neutron Capture Therapy

Cancer Research, 1987

Authors:   Jeffrey Coderre,John Glass,Ralph Fairchild,Uma Roy,Scott Cohen,Irwin Fand
Journal: Cancer Research
Abstract: Melanoma cells actively accumulate aromatic amino acids for use as precursors in the synthesis of the pigment melanin. Using the Harding-Passey melanoma carried s.c. in BALB/c mice, we have demonstrated that p-boronophenylalanine (BPA) is taken up by melanoma tissue to a much greater extent than by normal tissues. Following a single i.p. injection, or a series of injections given over 1 h, the accumulation of boron in melanoma was found to be transient, reaching a maximum approximately 6 h postinjection. The concentrations of boron achieved in tumor ranged from 9–33 µg/g, and are within the range estimated to be necessary for successful application of the nuclear reaction 10B(n,$alpha$)7Li for neutron capture therapy. Boron concentrations in tumor and tissues were determined using either a prompt-gamma spectroscopic technique or by quantitative neutron capture radiography using whole-body sections. Distribution studies with the resolved stereoisomers of BPA indicated that the l isomer is preferentially accumulated in the melanoma compared to the d isomer. The l isomer of BPA was shown to be targeted to actively dividing tumor cells by simultaneously comparing the boron and [3H]thymidine distribution in tumor. Under conditions which selectively deliver high concentrations of boron to Harding-Passey melanomas in BALB/c mice, BPA did not deliver useful concentrations of boron to a mammary adenocarcinoma in Hale-Stoner mice. These results, along with the selectivity of the Harding-Passey melanoma for the l isomer of BPA, are consistent with our working hypothesis that BPA is actively transported into the melanomas as an analogue of natural melanin precursors. textcopyright1987 American Association for Cancer Research.