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
Hauptverfasser: LeSauteur, Lynne, Cheung, Nai-Kong V, Lisbona, Robert, Saragovl, H. Uri
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container_end_page 1123
container_issue 9
container_start_page 1120
container_title Nature biotechnology
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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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source MEDLINE; Nature; Alma/SFX Local Collection
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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