Link E M, Carpenter R N
Department of Chemical Pathology, University College and Middlesex School of Medicine, London, England.
Cancer Res. 1992 Aug 15;52(16):4385-90.
The next stage of our preclinical investigations of targeted radiotherapy for melanoma with 3,7-(dimethylamino)phenazathionium chloride [methylene blue (MTB)] labeled with 211At (alpha particle emitter) concerns the treatment of cutaneous tumors and their metastases. Fragments of two human melanoma xenografts, highly pigmented HX118 and poorly pigmented HX34, implanted s.c. into nude mice, were treated with four doses of 211At-MTB injected i.v. The growth rate of cutaneous tumors and the appearance and size of their lymph node metastases served as criteria of treatment effectiveness. 211At-MTB inhibited the growth of cutaneous tumors in a manner dependent on their pigmentation and initial size. Highly pigmented smaller melanomas were affected by 211At-MTB to a greater extent than poorly pigmented and larger ones. Growth of the smallest HX118 lesions investigated was completely inhibited for 65 days, whereas the growth inhibition of HX34 tumors of the same size lasted 7 days only. 211At-MTB exhibited similar pigmentation-dependent effects toward lymph node metastases. The size of metastatic lesions derived from HX118 xenografts never reached that in control animals during the period of observation, whereas those grown from HX34 xenografts attained control values after a 50-day delay. The results demonstrated the capacity of 211At-MTB to control the growth of cutaneous melanomas and their metastases.
我们对用211At（α粒子发射体）标记的3,7-（二甲氨基）吩嗪鎓氯化物[亚甲蓝（MTB）]进行黑色素瘤靶向放射治疗的临床前研究的下一阶段涉及皮肤肿瘤及其转移灶的治疗。将两个人黑色素瘤异种移植瘤的片段，即高度色素沉着的HX118和色素沉着较差的HX34，皮下植入裸鼠，通过静脉注射给予四剂211At-MTB进行治疗。皮肤肿瘤的生长速率及其淋巴结转移灶的出现和大小作为治疗效果的标准。211At-MTB以依赖于其色素沉着和初始大小的方式抑制皮肤肿瘤的生长。高度色素沉着的较小黑色素瘤比较差色素沉着的较大黑色素瘤受211At-MTB的影响更大。所研究的最小的HX118病变的生长被完全抑制65天，而相同大小的HX34肿瘤的生长抑制仅持续7天。211At-MTB对淋巴结转移表现出类似的色素沉着依赖性效应。在观察期内，源自HX118异种移植瘤的转移灶大小从未达到对照动物的大小，而从HX34异种移植瘤生长的转移灶在延迟50天后达到对照值。结果证明了211At-MTB控制皮肤黑色素瘤及其转移灶生长的能力。
