title: Synthesis and binding affinity of a fluorine-substituted peroxisome proliferator-activated gamma (PPARgamma) ligand as a potential positron emission tomography (PET) imaging agent.
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.
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Lee
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.forename: Hsiaoju
authors.initials: H
authors.lastname: Lee
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
mesh_terms: D001577:Benzophenones / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry*; D005462:Fluorine Radioisotopes; D008024:Ligands; D047495:PPAR gamma / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
chemical_list: D001577:Benzophenones; D005462:Fluorine Radioisotopes; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005461:Fluorine; D014443:Tyrosine; C047723:benzophenone