Link E M, Michalowski A S, Rösch F
Department of Molecular Pathology, University College London Medical School, U.K.
Eur J Cancer. 1996 Oct;32A(11):1986-94. doi: 10.1016/0959-8049(96)00236-5.
The present stage of our preclinical investigations of targeted radiotherapy for melanoma with 3,7-(dimethylamino)phenazathionium chloride [methylene blue (MTB)] labelled with astatine-211 (211At), an alpha-particle emitter, concerns toxicity of the treatment, as well as macro- and microscopic evaluation of its efficacy. Fragments of two human melanoma xenografts, pigmented HX118 and non-pigmented HX34 (used as a control), were implanted s.c. into nude mice subsequently treated with two doses of 211At-MTB injected i.v. Alterations in tumour growth rate were related to microscopic damage caused by 211At-MTB to the lesions, as determined by light microscopy using histopathological techniques. 211At-MTB-dependent growth inhibition of pigmented melanoma occurred either instantly or as a gradual reduction in the tumour growth rate. At a later stage, lesions that ceased to grow immediately consisted of quiescent, heavily pigmented tumour cells, as well as advanced fibrosis, and were extensively infiltrated by melanin-laden phagocytes. Large, unresorbed and often calcified necrotic deposits characterised the tumours responding gradually to the treatment. 211At-MTB remained non-toxic in normal organs. Only a relative number of small lymphocytes in the groin lymph nodes in a minority of animals was temporarily reduced, most often in conjunction with the treatment of pigmented tumours. The data demonstrated a high therapeutic effectiveness of 211At-MTB towards pigmented melanoma at the expense of negligible injury to normal tissues, and revealed that the macroscopic determination of tumour growth rate often underestimated an efficacy of the applied treatment.
我们目前对用α粒子发射体砹-211（²¹¹At）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疗的临床前研究，涉及治疗的毒性以及对其疗效的宏观和微观评估。将两个人黑色素瘤异种移植瘤片段，色素沉着的HX118和无色素的HX34（用作对照），皮下植入裸鼠，随后用两剂静脉注射的²¹¹At-MTB进行治疗。肿瘤生长速率的变化与²¹¹At-MTB对病变造成的微观损伤有关，这是通过使用组织病理学技术的光学显微镜确定的。色素沉着黑色素瘤的²¹¹At-MTB依赖性生长抑制要么立即发生，要么表现为肿瘤生长速率逐渐降低。在后期，立即停止生长的病变由静止的、色素沉着严重的肿瘤细胞以及晚期纤维化组成，并被充满黑色素的吞噬细胞广泛浸润。大的、未吸收且常钙化的坏死沉积物是对治疗逐渐产生反应的肿瘤的特征。²¹¹At-MTB在正常器官中仍无毒。少数动物腹股沟淋巴结中只有相对数量的小淋巴细胞暂时减少，最常见于色素沉着肿瘤的治疗过程中。数据表明²¹¹At-MTB对色素沉着黑色素瘤具有高治疗效果，而对正常组织的损伤可忽略不计，并且揭示了肿瘤生长速率的宏观测定常常低估了所应用治疗的疗效。
