Sharkey Robert M, Chang Chien-Hsing, Rossi Edmund A, McBride William J, Goldenberg David M
Garden State Cancer Center at the Center for Molecular Medicine and Immunology, 300 The American Road, Morris Plains, 07950 NJ, USA.
Tumour Biol. 2012 Jun;33(3):591-600. doi: 10.1007/s13277-012-0367-6. Epub 2012 Mar 7.
Bispecific antibody pretargeting is a two-step procedure for selectively delivering radionuclides to tumors. The procedure was developed to solve a number of problems encountered when radionuclides are directly coupled to an IgG, such as slow blood clearance and delayed tumor accretion. While various forms of antibody fragments can reduce blood pool activity and provide faster tumor localization, tumor uptake is reduced considerably. In pretargeting procedures, the radionuclide is attached to a small molecule that quickly traverses the vascular barrier to reach the tumor cells, achieving maximum accretion within 0.5 to 1.0 h. Just as quickly, it is eliminated from the body, thereby minimizing tissue exposure and developing high tumor/tissue ratios very early. In order to capture the radionuclide in the tumor, a bispecific antibody (bsMAb) that binds to the tumor and to the isotope carrier (e.g., a hapten-peptide) is pre-administered some time earlier. The pretargeting procedure has been shown repeatedly to improve tumor localization as compared to directly radiolabeled antibodies, thereby enhancing both imaging and therapy. In this article, we review the progress our group has made toward developing and testing bsMAb pretargeting systems for cancer detection and therapy.
双特异性抗体预靶向是一种将放射性核素选择性递送至肿瘤的两步法。该方法旨在解决放射性核素直接偶联至IgG时遇到的一些问题，如血液清除缓慢和肿瘤摄取延迟。虽然各种形式的抗体片段可降低血池活性并实现更快的肿瘤定位，但肿瘤摄取会显著降低。在预靶向方法中，放射性核素与一个小分子相连，该小分子可快速穿过血管屏障到达肿瘤细胞，在0.5至1.0小时内实现最大摄取。同样迅速的是，它会从体内清除，从而使组织暴露最小化，并在很早的时候就形成高肿瘤/组织比。为了在肿瘤中捕获放射性核素，较早前预先给予一种与肿瘤和同位素载体（如半抗原-肽）结合的双特异性抗体（bsMAb）。与直接放射性标记抗体相比，预靶向方法已多次证明可改善肿瘤定位，从而增强成像和治疗效果。在本文中，我们回顾了我们团队在开发和测试用于癌症检测和治疗的bsMAb预靶向系统方面所取得的进展。
