title: Isomers of 4-[18F]fluoro-proline: radiosynthesis, biological evaluation and results in humans using PET.
abstract: Proline and hydroxyproline represent major constituents of mammalian structural proteins, especially of collagen. An efficient radiosynthesis of the (18)F-labeled proline derivatives cis-/trans-4-[(18)F]fluoro-L-proline was developed two decades ago with the aim to investigate various diseases with altered collagen synthesis using Positron-Emission- Tomography (PET). A number of studies have explored cis-4-[(18)F]fluoro-L-proline uptake in various pathologies associated with increased collagen formation and in neoplastic lesions, but so far the results have not been very promising. Trans-4-[(18)F]fluoro-L-proline has not yet been investigated in detail, however the compound exhibits considerable differences in metabolic behavior and biodistribution compared with its cis-enantiomer. In recent years, the D-isomers of cis- /trans-4-[(18)F]fluoro-proline have been considered as PET tracers as well, and it was observed that both exhibit a preferred uptake into the brain compared with their L-isomers. Surprisingly, a high uptake of cis-4-[(18)F]fluoro-D-proline was found in brain areas exhibiting secondary neurodegeneration as well as in areas of radionecrosis after treatment of brain tumors. In this article, the present knowledge on the biological and physiological properties of cis-/trans-4-[(18)F]fluoro-D/L-proline and the results in various pathologies are reviewed, including some previously unpublished results from our laboratory.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Geisler
authors.forename: Johannes
authors.initials: J
authors.lastname: Ermert
authors.forename: Gabriele
authors.initials: G
authors.lastname: Stoffels
authors.forename: Antje
authors.initials: A
authors.lastname: Willuweit
authors.forename: Norbert
authors.initials: N
authors.lastname: Galldiks
authors.forename: Christian P
authors.initials: CP
authors.lastname: Filss
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Shah
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Coenen
authors.affiliation: Institute of Neuroscience and Medicine, Forschungszentrum Jülich, D-52425 Jülich, Germany. k.j.langen@fz-juelich.de.
authors.forename: Karl-Josef
authors.initials: KJ
authors.lastname: Langen
mesh_terms: D001692:Biological Transport; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D002471:Cell Transformation, Neoplastic; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging*; D007536:Isomerism; D049268:Positron-Emission Tomography; D011392:Proline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011880:Radiotherapy Planning, Computer-Assisted; D015203:Reproducibility of Results; D051598:Whole Body Imaging
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C431803:fluoro-proline; D011392:Proline