Synthesis, radiolabeling and preliminary in vivo evaluation of [18F]FE-PE2I, a new probe for the dopamine transporter.
A new dopamine transporter (DAT) ligand, (E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane (FE-PE2I, 6), derived from PE2I (1), was prepared and found to be a potent inhibitor of rodent DAT in vitro. Compound 6 was radiolabelled with fluorine-18 (t(1/2)=109.8 min) for PET studies in monkeys. In vivo PET measurements showed a regional distribution in brain that corresponds to the known distribution of DAT. This binding was specific, reversible and the kinetics of [(18)F]6 binding in brain were faster than for its lead compound, [(11)C]1. The possible presence of a hydroxymethyl-radiometabolite formed by oxidation in the 3beta-benzylic position of [(18)F]6 warrants further detailed evaluation of the metabolism of [(18)F]6. [(18)F]6 is a potential radioligand for imaging DATs in the human brain with PET.
Schou
Magnus
M
Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden. magnus.schou@astrazeneca.com
Steiger
Carsten
C
Varrone
Andrea
A
Guilloteau
Denis
D
Halldin
Christer
C
D000818:Animals; D001921:Brain / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry; D000882:Haplorhini; D006801:Humans; D007553:Isotope Labeling; D007700:Kinetics; D009662:Nortropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats
C543996:(E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D009662:Nortropanes; D019275:Radiopharmaceuticals