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...
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Veröffentlicht in: | Nature biotechnology 1996-09, Vol.14 (9), p.1120-1123 |
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creator | LeSauteur, Lynne Cheung, Nai-Kong V Lisbona, Robert Saragovl, H. Uri |
description | 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. |
doi_str_mv | 10.1038/nbt0996-1120 |
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Uri</creatorcontrib><title>Small molecule nerve growth factor analogs image receptors in vivo</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><description>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. 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subjects | 3T3 Cells Animals Antibodies, Monoclonal Biological and medical sciences Biotechnology Gene Expression Humans Investigative techniques, diagnostic techniques (general aspects) Medical sciences Mice Mice, Nude Miscellaneous. Technology Neoplasms, Experimental - diagnosis Neoplasms, Experimental - genetics Neoplasms, Experimental - therapy Nerve Growth Factors - chemistry Nerve Growth Factors - metabolism Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Radioligand Assay Radionuclide investigations Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism Receptor, trkA Receptors, Nerve Growth Factor - genetics Receptors, Nerve Growth Factor - metabolism Technetium Tissue Distribution Transfection |
title | Small molecule nerve growth factor analogs image receptors in vivo |
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