Small molecule nerve growth factor analogs image receptors in vivo.
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.
LeSauteur
L
L
McGill University, Department of Pharmacology and Therapeutics, USA.
Cheung
N K
NK
Lisbona
R
R
Saragovi
H U
HU
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal; D001709:Biotechnology; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D009414:Nerve Growth Factors / Q000737:chemistry / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011869:Radioligand Assay; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D013667:Technetium; D014018:Tissue Distribution; D014162:Transfection
D000911:Antibodies, Monoclonal; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D013667:Technetium; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA