Biodistribution of boron concentration on melanoma-bearing hamsters after administration of p-, m-, o-boronophenylalanine

Although p-boronophenylalanine (p-BPA), a boronate analogue of tyrosine, ha s proven to be one of the most successful compounds for boron neutron captu re therapy (BNCT) of malignant melanoma, the selective uptake mechanism of this compound into melanoma cells is not well understood. Therefore, the re lationship between the structure of BPA and its specific affinity to melano ma cells appears worthy of investigation. In the present study, m- and o-bo ronophenylalanine (m- and o-BPA) were administered to melanoma-bearing hams ters and their uptake was measured, The time courses (0.5, 2.0, 4.0 and 48. 0 h) of boron concentrations in melanoma, normal skin, and blood were deter mined in male Syrian (golden) hamsters bearing Greene's melanomas following a single intraperitoneal injection of either p-, m- or o-BPA (100 mg/kg of BPA.fructose in 1.0 ml of saline), The boron concentrations in these tissu es were measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES), In melanoma, the order of boron uptake was p->m->o-BPA at all t ime points, and the boron concentrations obtained with p-BPA and m-BPA rese mbled each other in that they had a peak at 2 h after administration and de creased with time, The melanoma/skin boron concentration ratio of p-BPA had a peak at 4 h after administration and the ratio ranged between 7/1 and 8/ 1, On the other hand, m-BPA and o-BPA had a peak at 2 h and their ratios ra nged between 4/1 and 5/1, The difference in the accumulations of p-BPA and m-DPA could be due to a difference in the property of p-BPA as a tyrosine a nalogue for melanin synthesis. The accumulation of m-BPA into melanoma migh t indicate the baseline level of metabolism-related amino acid transport. O ur experimental findings indicate that this melanin synthesis, or the struc tural analogy between the boron compound and tyrosine as a precursor of mel anin, is an important Factor in the increased accumulation of p-BPA in mela noma cells.