title: Radioiodinated dechloro-4-iodofenofibrate: a hydrophobic model drug for molecular imaging studies.
abstract: Radiolabeling is a valuable option for tracking drug molecules in biodistribution experiments. In the development of innovative drug delivery systems the influence of the pharmaceutical formulation on the drugs' pharmacokinetics has to be investigated. The hypolipidemic agent fenofibrate is an ideal model drug for testing the performance of drug delivery systems designed for poorly soluble compounds. Herein, we report a de novo synthesis of a fenofibrate derivative, dechloro-4-iodofenofibrate, as well as its conversion into its radioiodinated derivatives containing (125)I or (131)I. The enzymatic stability of the radiolabeled compounds synthesized was determined in vitro. A scintigraphic imaging study supplemented by biodistribution experiments and analysis of excreted metabolites revealed the stability required for in vivo applications and its similarity to fenofibrate. Therefore a convenient method is presented to synthesize radioiodinated derivatives of fenofibrate. These tracers show excellent in vitro and in vivo properties to study the behavior of lipophilic drugs.
authors.affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Breyer
authors.forename: Angelika
authors.initials: A
authors.lastname: Semmler
authors.forename: Tobias
authors.initials: T
authors.lastname: Miller
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hill
authors.forename: Simon
authors.initials: S
authors.lastname: Geissler
authors.forename: Uwe
authors.initials: U
authors.lastname: Haberkorn
authors.forename: Walter
authors.initials: W
authors.lastname: Mier
mesh_terms: D000818:Animals; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D008099:Liver / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D011849:Radioactive Tracers; D044967:Serum / Q000378:metabolism; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000960:Hypolipidemic Agents; D007457:Iodine Radioisotopes; D011849:Radioactive Tracers; D011345:Fenofibrate