title: Biodistribution of boron concentration on melanoma-bearing hamsters after administration of p-, m-, o-boronophenylalanine.
abstract: Although p-boronophenylalanine (p-BPA), a boronate analogue of tyrosine, has proven to be one of the most successful compounds for boron neutron capture therapy (BNCT) of malignant melanoma, the selective uptake mechanism of this compound into melanoma cells is not well understood. Therefore, the relationship between the structure of BPA and its specific affinity to melanoma cells appears worthy of investigation. In the present study, m- and o-boronophenylalanine (m- and o-BPA) were administered to melanoma-bearing hamsters 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 determined 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 tissues 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 time points, and the boron concentrations obtained with p-BPA and m-BPA resembled each other in that they had a peak at 2 h after administration and decreased 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 ranged between 4/1 and 5/1. The difference in the accumulations of p-BPA and m-BPA could be due to a difference in the property of p-BPA as a tyrosine analogue for melanin synthesis. The accumulation of m-BPA into melanoma might indicate the baseline level of metabolism-related amino acid transport. Our experimental findings indicate that this melanin synthesis, or the structural analogy between the boron compound and tyrosine as a precursor of melanin, is an important factor in the increased accumulation of p-BPA in melanoma cells.
authors.affiliation: Department of Radiation Oncology, Kawasaki Medical School, Matsushima, Kurashiki 701-0192, Japan. hiratuka@med.kawasaki-m.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Hiratsuka
authors.forename: K
authors.initials: K
authors.lastname: Yoshino
authors.forename: H
authors.initials: H
authors.lastname: Kondoh
authors.forename: Y
authors.initials: Y
authors.lastname: Imajo
authors.forename: Y
authors.initials: Y
authors.lastname: Mishima
mesh_terms: D000818:Animals; D001895:Boron / Q000493:pharmacokinetics*; D001896:Boron Compounds / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D006224:Cricetinae; D008297:Male; D008543:Melanins / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000628:therapy; D008647:Mesocricetus; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D001896:Boron Compounds; D008543:Melanins; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; D001895:Boron; C033685:4-boronophenylalanine