LeSauteur L, Cheung N K, Lisbona R, Saragovi H U
McGill University, Department of Pharmacology and Therapeutics, USA.
Nat Biotechnol. 1996 Sep;14(9):1120-2. doi: 10.1038/nbt0996-1120.
The in vivo targeting efficacy of small molecule analogs of nerve growth factor (NGF) that bind the NGF receptor p140 TrkA was evaluated and compared with that of a high-affinity anti-TrkA monoclonal antibody (Mab 5C3). Nuclear imaging studies were done after the injection of 99mTc-labeled compounds in nude mice bearing tumors. Kinetics of tumor targetting, blood clearance, and bioavailability of NGF mimics were equivalent or better than Mab 5C3. Tumors that do not express TrkA were not targeted, demonstrating the specificity of NGF mimics in vivo. This comparative biodistribution study demonstrates that receptor-specific small molecule analogs designed from large polypeptides may be more useful than antibodies and may be effective agents for the detection, diagnosis, and possible treatment of neoplasias involving overexpressed oncogenic receptors such as TrkA.
评估了与神经生长因子（NGF）受体p140 TrkA结合的NGF小分子类似物的体内靶向效能，并与高亲和力抗TrkA单克隆抗体（Mab 5C3）的效能进行了比较。在向荷瘤裸鼠注射99mTc标记的化合物后进行了核成像研究。NGF模拟物的肿瘤靶向动力学、血液清除率和生物利用度与Mab 5C3相当或更佳。不表达TrkA的肿瘤未被靶向，这证明了NGF模拟物在体内的特异性。这项比较生物分布研究表明，由大的多肽设计的受体特异性小分子类似物可能比抗体更有用，并且可能是检测、诊断以及可能治疗涉及TrkA等过表达致癌受体的肿瘤的有效药物。
