Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor
Improved tumor imaging and therapy via i.v. IgG-mediated time-sequential modulation of neonatal Fc receptor
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DOI：
10.1172/jc132226
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发表时间：
2007-09-01
影响因子：
15.9
通讯作者：
Scheinberg, David A.
中科院分区：
文献类型：
--
作者：
Jaggi, Jaspreet Singh;Carrasquillo, Jorge A.;Scheinberg, David A.
IgG的长血浆半衰期，虽然允许增强肿瘤对肿瘤靶向IgG偶联物的摄取，但也导致背景活性和正常组织毒性增加。因此，成功的结合抗体的治疗用途仅限于高度敏感和容易接近的造血肿瘤。我们报告了一种治疗策略，通过使用高剂量IgG治疗对新生儿Fc受体（FcRn）的药理抑制，有益地改变IgG抗体的药代动力学。igg处理的小鼠显示出增强的血液和全身对放射性的清除，导致更好的肿瘤-血液图像对比和正常组织免受辐射的保护。肿瘤摄取和由此产生的治疗反应没有改变。此外，我们展示了这种方法在人类肿瘤成像中的应用，并讨论了它在癌症成像和治疗中的潜在应用。通过降低偶联IgG抗体输注后的血清持久性，可以提高其治疗指标，从而提高治疗和诊断效果。
The long plasma half-life of IgG, while allowing for enhanced tumor uptake of tumor-targeted IgG conjugates, also results in increased background activity and normal-tissue toxicity. Therefore, successful therapeutic uses of conjugated antibodies have been limited to the highly sensitive and readily accessible hematopoietic tumors. We report a therapeutic strategy to beneficially alter the pharmacokinetics of IgG antibodies via pharmacological inhibition of the neonatal Fc receptor (FcRn) using high-dose IgG therapy. IgG-treated mice displayed enhanced blood and whole-body clearance of radioactivity, resulting in better tumor-to-blood image contrast and protection of normal tissue from radiation. Tumor uptake and the resultant therapeutic response was unaltered. Furthermore, we demonstrated the use of this approach for imaging of tumors in humans and discuss its potential applications in cancer imaging and therapy. The ability to reduce the serum persistence of conjugated IgG antibodies after their infusion can enhance their therapeutic index, resulting in improved therapeutic and diagnostic efficacy.