Link E M, Carpenter R N, Hansen G
Department of Molecular Pathology, University College, London, U.K.
Eur J Cancer. 1996 Jun;32A(7):1240-7. doi: 10.1016/0959-8049(96)00023-8.
3,7-(dimethylamino) phenazathionium chloride [methylene blue (MTB)] labelled with alpha-particle emitter astatine-211 (211At) selectively accumulates in melanoma cells due to an exceptionally high affinity of MTB to melanin, and proves to be a very effective agent in targeting radiotherapy for pigmented human melanoma grown in mice. This study aimed at a selection of the most advantageous [211At]MTB dose fractionation leading to irreversible regression of the treated lesions. Nude mice bearing subcutaneous human melanoma xenografts of either highly pigmented HX118 or poorly pigmented HX34 human melanoma were treated with [211At]MTB administered intravenously. The treatment was performed using three different schedules of [211At]MTB fractionation: a single large dose, five fractions delivered sequentially every 48 h and two to five fractions given with a mean frequency of one per week. The effectiveness of [211At]MTB treatment was assessed by determination of the growth rate of cutaneous tumours and length of time between tumour implantation and killing of moribund mice. [211At]MTB applied with a mean frequency of one fraction per week appeared to be the most efficient treatment for highly pigmented HX118 melanomas. Its effectiveness was dependent on [211At]MTB activity used per fraction and the size of the cutaneous tumours at the beginning of the treatment. A total dose of [211At]MTB seemed of less importance. An irreversible regression of the lesions was achieved. Poorly pigmented cutaneous melanoma xenografts were affected most significantly by [211At]MTB applied as five fractions given every 48 h. The treatment caused a temporary inhibition of tumour growth after which the lesions regained the control growth rate. These and previous results suggest that [211At]MTB could successfully control the growth of already formed lesions of pigmented melanoma, as well as prevent metastatic spread of the tumour, provided an appropriate fractionation régime of the radiolabelled compound is employed.
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）]，由于MTB对黑色素具有极高的亲和力，可选择性地积聚在黑色素瘤细胞中，并且被证明是针对在小鼠体内生长的人类色素沉着性黑色素瘤进行靶向放射治疗的非常有效的药物。本研究旨在选择最有利的[²¹¹At]MTB剂量分割方案，以导致治疗病变的不可逆消退。对携带高色素沉着的HX118或低色素沉着的HX34人黑色素瘤皮下异种移植瘤的裸鼠静脉注射[²¹¹At]MTB进行治疗。使用三种不同的[²¹¹At]MTB分割方案进行治疗：单次大剂量、每48小时依次给予五剂以及平均每周一剂给予两至五剂。通过测定皮肤肿瘤的生长速率以及肿瘤植入至濒死小鼠死亡之间的时间长度来评估[²¹¹At]MTB治疗的有效性。对于高色素沉着的HX118黑色素瘤，平均每周一剂[²¹¹At]MTB似乎是最有效的治疗方法。其有效性取决于每剂使用的[²¹¹At]MTB活性以及治疗开始时皮肤肿瘤的大小。[²¹¹At]MTB的总剂量似乎不太重要。实现了病变的不可逆消退。每48小时给予五剂的[²¹¹At]MTB对低色素沉着的皮肤黑色素瘤异种移植瘤影响最为显著。该治疗导致肿瘤生长暂时受到抑制，之后病变恢复到对照生长速率。这些结果以及之前的结果表明，只要采用放射性标记化合物的适当分割方案，[²¹¹At]MTB可以成功控制已形成的色素沉着性黑色素瘤病变的生长，并预防肿瘤的转移扩散。
