Improving the delivery of radionuclides for imaging and therapy of cancer using pretargeting methods
Improving the delivery of radionuclides for imaging and therapy of cancer using pretargeting methods
复制标题
DOI：
10.1158/1078-0432.ccr-1004-0009
复制
发表时间：
2005-10-01
影响因子：
11.5
通讯作者：
Goldenberg, DM
中科院分区：
文献类型：
--
作者：
Sharkey, RM;Karacay, H;Goldenberg, DM
本文回顾了癌症成像和放射性核素治疗的预靶向的背景和现状。类似于 20 年前引入的预靶向程序是作为直接放射性标记抗体的替代方案。由于它们是多步骤过程，因此遇到了阻力，但后来发展到简单且改进的程序，可能成为下一代放射性核素成像和治疗。放射性标记化合物与抗体靶向剂的分离为放射性标记过程中的预靶向程序提供了相当大的灵活性，为使用γ或正电子发射放射性核素以及治疗应用的各种β和α发射放射性核素进行分子成像提供了机会。预靶向方法改善了肿瘤/非肿瘤比率，超过了直接放射性标记的 Fab' 片段所达到的效果，特别是在放射性核素注射后的短短几个小时内。此外，肿瘤摄取超过 Fab' 片段多达 10 倍，使预靶向成像的灵敏度大大增强。分子生物学的进步导致了新型结合蛋白的开发，进一步改善了这些系统中放射性核素的输送。各种血液学和实体瘤模型的研究表明，与直接放射性标记的 IgG 治疗相比，预靶向具有优势，并且正在进行的几项临床研究也显示出有希望的结果。因此，下一代靶向剂可能会采用预靶向方法来优化放射性核素的递送，以适应广泛的应用。
The article reviews the background and current status of pretargeting for cancer imaging and therapy with radionuclides. Pretargeting procedures were introduced similar to 20 years ago as an alternative to directly radiolabeled antibodies. Because they were multistep processes, they were met with resistance but have since progressed to simple and improved procedures that could become the next generation of imaging and therapy with radionuclides. The separation of the radiolabeled compound from the anti body-targeting agent affords pretargeting procedures considerable flexibility in the radiolabeling process, providing opportunities for molecular imaging using gamma- or positron-emitting radionuclides and a variety of beta- and alpha-emitting radionuclides of therapeutic applications. Pretargeting methods improve tumor/ nontumor ratios, exceeding that achieved with directly radiolabeled Fab' fragments, particularly within just a few hours of the radionuclide injection. In addition, tumor uptake exceeds that of a Fab' fragment by as much as 10-fold, giving pretargeting a greatly enhanced sensitivity for imaging. Advances in molecular biology have led to the development of novel binding proteins that have further improved radionuclide delivery in these systems. Studies in. a variety of hematologic and solid tumor models have shown advantages of pretargeting compared with directly radiolabeled IgG for therapy, and there are several clinical studies under way that are also showing promising results. Thus, the next generation of targeting agents will likely employ pretargeting approaches to optimize radionuclide delivery for a wide range of applications.