Coderre J A, Glass J D, Fairchild R G, Roy U, Cohen S, Fand I
Medical Department, Brookhaven National Laboratory, Upton, New York 11973.
Cancer Res. 1987 Dec 1;47(23):6377-83.
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 micrograms/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.
黑色素瘤细胞会主动积累芳香族氨基酸，用作合成色素黑色素的前体。利用在BALB/c小鼠皮下携带的哈丁-帕西黑色素瘤，我们已证明对硼苯丙氨酸（BPA）被黑色素瘤组织摄取的程度远高于正常组织。单次腹腔注射或在1小时内进行一系列注射后发现，黑色素瘤中硼的积累是短暂的，在注射后约6小时达到最大值。肿瘤中达到的硼浓度范围为9 - 33微克/克，处于估计对成功应用核反应10B(n,α)7Li进行中子俘获治疗所需的范围内。使用瞬发γ光谱技术或通过对全身切片进行定量中子俘获射线照相来测定肿瘤和组织中的硼浓度。对BPA拆分的立体异构体进行的分布研究表明，与D异构体相比，L异构体在黑色素瘤中优先积累。通过同时比较肿瘤中硼和[3H]胸腺嘧啶的分布，表明BPA的L异构体靶向于活跃分裂的肿瘤细胞。在选择性地将高浓度硼输送到BALB/c小鼠的哈丁-帕西黑色素瘤的条件下，BPA并未将有用浓度的硼输送到黑尔-斯托纳小鼠的乳腺腺癌中。这些结果，连同哈丁-帕西黑色素瘤对BPA的L异构体的选择性，与我们的工作假设一致，即BPA作为天然黑色素前体的类似物被主动转运到黑色素瘤中。
