Synthesis and binding affinity of a fluorine-substituted peroxisome proliferator-activated gamma (PPARgamma) ligand as a potential positron emission tomography (PET) imaging agent |
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Authors: | Lee Byung Chul Lee Kyo Chul Lee Hsiaoju Mach Robert H Katzenellenbogen John A |
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Affiliation: | Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA. |
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Abstract: | The peroxisome proliferator-activated receptor gamma (PPARgamma) is an important regulator of lipid metabolism and the differentiation of pre-adipocytes. Thus, imaging PPARgamma in vivo using positron-emission tomography (PET) might be useful in assessing lipid metabolism disorders and identifying tumor cell differentiation. A fluorine-substituted PPARgamma ligand from tyrosine-benzophenone class, compound 1, has a very high affinity for PPARgamma receptor (Ki = 0.14 nM). To develop this compound as a PPARgamma PET imaging agent, we investigated synthetic routes suitable for its labeling with the short-lived PET radionuclide fluorine-18 (t1/2 = 110 min). To obtain the high specific activity material needed for receptor imaging with this isotope, reactions need to proceed efficiently, within a short time, starting from fluoride ion at the tracer level. The most promising approach involves introduction of fluorine into a suitable benzophenone precursor, followed by efficient coupling of this intermediate with the heterocyclic tyrosine component using a copper-catalyzed Ullmann-type condensation. |
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