title: Synthesis and evaluation of novel N-fluoropyridyl derivatives of tropane as potential PET imaging agents for the dopamine transporter.
abstract: A series of novel N-fluoropyridyl-containing tropane derivatives were synthesized and their binding affinities for the dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine (NET) were determined via competitive radioligand binding assays. Among these derivatives, compound 6d showed the highest binding affinity to DAT (K(i)=4.1 nM), and selectivity for DAT over SERT (5-fold) and NET (16-fold). Compound 6d was radiolabeled with Fluorine-18 in two steps. Regional brain distribution and ex vivo autoradiography studies of [(18)F]6d demonstrated that the ligand was selectively localized in the striatum region, where DAT binding sites are highly expressed. [(18)F]6d may be useful as a potential radioligand for imaging DATs with PET.
authors: Key Laboratory of Radiopharmaceuticals (Beijing Normal University), Ministry of Education, Beijing 100875, PR China.
authors: Jingying
authors: J
authors: Liu
authors: Lin
authors: L
authors: Zhu
authors: Karl
authors: K
authors: Plössl
authors: Brian P
authors: BP
authors: Lieberman
authors: Hank F
authors: HF
authors: Kung
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003952:Diagnostic Imaging; D050483:Dopamine Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014326:Tropanes / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D011725:Pyridines; D014326:Tropanes