METAL CHELATE CONJUGATED MONOCLONAL ANTIBODIES FOR TUMOR DIAGNOSIS AND THERAPY

“肿瘤相关的单抗(MAb)是 潜在的治疗药物作为细胞毒药物的选择性载体 到恶性细胞。这一假设在动物模型系统中得到了验证。 针对与多种病毒相关的抗原的单抗 恶性肿瘤。所使用的细胞杀伤剂有多种 放射性核素。它们结合时的相对效力 对单抗进行检测，并与单抗进行比较 单抗，用I-131放射性标记，或 与毒素结合在一起。选择研究的几种放射性核素 跨越可用的放射性核素特性的范围，从而分析 发射能量、半衰期和物理效应 排放的特性。研究继续集中在 扩大Y-90的临床应用及完成临床前工作 发射放射性核素的阿尔法粒子的研究， BI-213，和-211。美国国立卫生研究院目前正在进行的临床试验 采用第二代双功能络合剂 1B4M-DTPA(又名MX-DTPA)，用于封存Y-90。近期 螯合设计技术的结果揭示了体内的一种 双官能团绝对构型的依赖性 用于优化放射性金属络合物稳定性的络合剂。由于 这些结果，所有目前涉及In-111，稀土离子的努力， 和Bi-212,213已被转换为与 CHX-A‘’DTPA。未来的临床试验，如计划中的试验 7G7单抗联合人源化抗Tac治疗 ATL的治疗，然后将使用该配体。另外， 将AT-211投入临床的初步努力已经 新链接器的开发被证明是积极的，基于 三烷基-锡基化学在At-211上的亲电置换 并将人源化的抗Tac作为卤素进行放射性标记。

"Tumor associated monoclonal antibodies (mAb) are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. This hypothesis is tested in animal model systems with mAbs directed toward antigens associated with a variety of malignancies. The cytocidal agents being employed are various radionuclides. Their relative efficacy when conjugated to monoclonal antibodies is assayed and compared to that of monoclonal antibodies alone, radiolabeled with I-131, or conjugated to toxins. The several radionuclides chosen for study span the range of radionuclidic properties available thereby assaying the effects of energy of emission, half-life, and physical characteristics of emission. Research continues to focus on expanding clinical use of Y-90 and on completing pre-clinical studies with the alpha-particle emitting radionuclides Bi-212, Bi-213, and At-211. The ongoing clinical trials at the NIH currently employ the second generation bifunctional chelating agent 1B4M-DTPA (aka MX-DTPA) for sequestering Y-90. Recent results in chelate design technology have revealed an in vivo dependency of the absolute configuration of the bifunctional chelating agent to optimize radio-metal complex stability. Due to these results, all current efforts involving In-111, lanthanide ions, and Bi-212,213 have been converted to being performed with CHX-A'' DTPA. Future clinical trials, such as those being planned with mAb 7G7 in conjunction with humanized anti-Tac for the treatment of ATL, would then employ this ligand. Additionally, preliminary efforts toward bringing At-211 into clinical use have proven positive with the development of new linkers based upon trialkyl-stannyl chemistry for electrophilic displacement by At-211 and radiolabeling humanized anti-Tac treating At as a halogen."