Development of novel epidermal growth receptor-basedradiopharmaceuticals: Imaging agents for breast cancer

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The goal of this research was to develop epidermal growthfactor receptor (EGFR) nuclear medicine breast cancer imaging agents. Ourapproach was to synthesize small molecule inhibitors of the EGFR tyrosinekinase (tk) suitable for labeling with single photon or positron-emittingradioisotopes and evaluate the imaging potential of these new molecules.We have synthesized and fully characterized 22 quinazoline compounds. Allcompounds inhibit EGFR tk phosphorylation activity in the nanomolarrange. All compounds tested exhibited specificity for the EGFR tk versusthe ErbB2 and ErbB4 tyrosine kinases. A radiometric binding assay usingan iodine-125 labeled quinazoline was developed to determine the affinityof the quinazolines for the EGFR tk ATP ... continued below

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Van Brocklin, Henry F. September 25, 2001.

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The goal of this research was to develop epidermal growthfactor receptor (EGFR) nuclear medicine breast cancer imaging agents. Ourapproach was to synthesize small molecule inhibitors of the EGFR tyrosinekinase (tk) suitable for labeling with single photon or positron-emittingradioisotopes and evaluate the imaging potential of these new molecules.We have synthesized and fully characterized 22 quinazoline compounds. Allcompounds inhibit EGFR tk phosphorylation activity in the nanomolarrange. All compounds tested exhibited specificity for the EGFR tk versusthe ErbB2 and ErbB4 tyrosine kinases. A radiometric binding assay usingan iodine-125 labeled quinazoline was developed to determine the affinityof the quinazolines for the EGFR tk ATP binding site. The affinitiesranged from 0.4-51 nM. The octanol/water partition coefficients (Log P;lipophilicity) of the new compounds ranged from 2.2-5.5. Six compoundshave been labeled with fluorine-18. Biodistribution in EGFRoverexpressing tumor bearing mice demonstrated tumor uptake buthighlighted delivery and metabolism issues. The 2-fluoro quinazoline wasnot metabolized in an in vitro hepatocyte study. From this work a breadthof agent characteristics was created establishing the foundation forfuture research toward the optimal EGFR imaging agent.

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  • Report No.: LBNL--49197
  • Report No.: BG96-328
  • Grant Number: DE-AC02-05CH11231
  • DOI: 10.2172/920326 | External Link
  • Office of Scientific & Technical Information Report Number: 920326
  • Archival Resource Key: ark:/67531/metadc895427

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  • September 25, 2001

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  • Sept. 27, 2016, 1:39 a.m.

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  • Dec. 9, 2016, 9:17 p.m.

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Van Brocklin, Henry F. Development of novel epidermal growth receptor-basedradiopharmaceuticals: Imaging agents for breast cancer, report, September 25, 2001; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc895427/: accessed September 24, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.