Link E M
Department of Molecular Pathology, University College London Medical School, UK.
Hybridoma. 1999 Feb;18(1):77-82. doi: 10.1089/hyb.1999.18.77.
The increasing incidence of melanoma and a lack of effective therapy have stimulated a search for new methods of early detection and treatment of the disease. Melanin synthesized in melanoma cells presents a unique target to which the treatment can be selectively addressed, provided the pigment is recognized by a suitable drug. Methylene blue possesses a high affinity for melanin and, therefore, accumulates preferentially in melanoma cells. Since not directly toxic to the tumor, methylene blue serves as a carrier for radioisotopes and, once taken up by melanoma cells, acts as a selectively localized source of radiation. Hence, radioderivatives of the compound can be used for diagnosis and therapy of disseminated melanoma. 131I-methylene blue in conjunction with gamma camera imaging has already proved in clinical studies to be a useful tool for the detection of early melanoma dissemination. 211At-methylene blue exceptional efficacy in treating melanoma and preventing its metastatic spread without damaging normal structures when administered systemically to human melanoma-bearing mice led to the approval of this alpha-particle emitting methylene blue derivative for the Phase I clinical trial.
黑色素瘤发病率的不断上升以及缺乏有效的治疗方法，促使人们寻找早期检测和治疗该疾病的新方法。黑色素瘤细胞中合成的黑色素呈现出一个独特的靶点，只要色素能被合适的药物识别，治疗就能针对该靶点进行选择性处理。亚甲蓝对黑色素具有高亲和力，因此优先在黑色素瘤细胞中积累。由于亚甲蓝对肿瘤无直接毒性，它可作为放射性同位素的载体，一旦被黑色素瘤细胞摄取，就作为辐射的选择性定位源发挥作用。因此，该化合物的放射性衍生物可用于播散性黑色素瘤的诊断和治疗。临床研究已证明，131I-亚甲蓝结合γ相机成像对于检测早期黑色素瘤播散是一种有用的工具。当对荷人黑色素瘤小鼠进行全身给药时，211At-亚甲蓝在治疗黑色素瘤并防止其转移扩散方面具有非凡疗效，且不会损害正常组织，这使得这种发射α粒子的亚甲蓝衍生物获批进入I期临床试验。
