Biodistribution of boron concentration on melanoma-bearing hamsters after administration of p-, m-, o-boronophenylalanine
Biodistribution of boron concentration on melanoma-bearing hamsters after administration of p-, m-, o-boronophenylalanine
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DOI：
10.1111/j.1349-7006.2000.tb00965.x
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发表时间：
2000-04-01
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影响因子：
--
通讯作者：
Mishima, Y
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文献类型：
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作者：
Hiratsuka, J;Yoshino, K;Mishima, Y
虽然对硼苯丙氨酸（p-BPA）是酪氨酸的硼酸类似物，已被证明是恶性黑色素瘤硼中子俘获治疗（BNCT）最成功的化合物之一，但该化合物进入黑色素瘤细胞的选择性摄取机制尚不清楚。因此，BPA的结构与其对黑色素瘤细胞的特异性亲和力之间的关系似乎值得研究。在本研究中，我们将m-和o-硼苯丙氨酸（m-和o-BPA）给予患有黑素瘤的仓鼠，并测量它们的摄取情况。在患有格林黑素瘤的雄性叙利亚（金色）仓鼠中，通过单次腹腔注射p-、m-或o-BPA （100 mg/kg bpa，果糖加入1.0 ml生理盐水中），测定黑素瘤、正常皮肤和血液中硼浓度的时间过程（0.5、2.0、4.0和48.0 h）。这些组织的硼浓度是衡量电感耦合等离子体原子发射光谱法(icp - aes),在黑素瘤,硼的吸收量的顺序是p - > m - > o-BPA时间点,和获得的硼浓度p-BPA m-BPA像对方,他们有一个峰值在2 h后管理和降低随着时间的推移,皮肤黑素瘤/硼浓度比p-BPA高峰在4 h后管理和之间的比率范围7/1和8/1,另一方面，m-BPA和o-BPA在2 h达到峰值，其比值在4/1和5/1之间。p-BPA和m-DPA积累的差异可能是由于p-BPA作为酪氨酸类似物合成黑色素的性质不同。m-BPA在黑色素瘤中的积累可能表明代谢相关氨基酸运输的基线水平。我们的实验结果表明，这种黑色素合成，或者硼化合物和酪氨酸之间的结构相似，作为黑色素的前体，是黑色素瘤细胞中p-BPA积累增加的重要因素。
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-DPA 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.