SMALL-MOLECULE NERVE GROWTH-FACTOR ANALOGS IMAGE RECEPTORS IN-VIVO

The in vivo targeting efficacy of small molecule analogs of nerve grow th 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 Tc- 90m-labeled compounds in nude mice bearing tumors. Kinetics of tumor t argetting, blood clearance, and bioavailability of NGF mimics were equ ivalent or better than Mab 5C3. Tumors that do not express TrkA were n ot 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 u seful than antibodies and may be effective agents for the detection, d iagnosis, and possible treatment of neoplasias involving overexpressed oncogenic receptors such as TrkA.