In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers
In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers
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DOI：
10.1016/s1040-8428(01)00113-5
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发表时间：
2001-07-01
影响因子：
6.2
通讯作者：
Ranson, M
中科院分区：
文献类型：
--
作者：
Allen, BJ;Rizvi, S;Ranson, M
靶向阿尔法治疗(TAT)可以通过选择性地杀死孤立的和血管生成前期的癌细胞簇来抑制微转移的生长。放射同位素TB-149和Bi-213分别与肿瘤特异性单抗形成抗黑色素瘤、白血病、前列腺癌和结直肠癌的α-免疫结合物(AIC)，与纤溶酶原激活物抑制物-2(PAI2)形成抗乳腺癌和前列腺癌的α-PAI2(API)。这些结合物在体外具有高度的稳定性、特异性和细胞毒性。皮下接种癌细胞2天后，未治疗对照组和非特异性AIC/API裸鼠模型均观察到黑色素瘤和乳腺癌的生长。局部注射AIC和API可完全抑制黑色素瘤和乳腺癌的生长。已确诊的黑色素瘤的皮内TAT显示，100亩Ci注射AIC后，所有黑色素瘤均消退。这些结果表明，局部和全身TAT在转移性癌症治疗中具有潜在的应用价值。(C)2001爱思唯尔爱尔兰科学有限公司。保留所有权利。
Targeted alpha therapy (TAT) can inhibit the growth of micrometastases by, selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 were chelated to cancer specific monoclonal antibodies to form alpha-immunoconjugates (AIC) against melanoma, leukaemia, prostate and colorectal cancer, and to the plasminogen activator inhibitor type-2 (PAI2) to form alpha-PAI2 (API) against breast and prostate cancer. These conjugates were found to be highly stable, specific and cytotoxic in vitro. Melanoma and breast cancer tumour growth was observed in nude mouse models for untreated controls and non-specific AIC/API at 2 days post-subcutaneous inoculation of cancer cells. Complete inhibition of melanoma and breast cancer growth was found for local injections of AIC and API, respectively. Intra-lesional TAT of established melanoma showed that all melanomas regressed with 100 mu Ci injections of AIC. These results point to the potential application of local and systemic TAT in the management of metastatic cancer. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.