title: Synthesis of 18F-labelled 2-(4'-fluorophenyl)-1,3-benzothiazole and evaluation as amyloid imaging agent in comparison with [11C]PIB.
abstract: 2-(4'-[(18)F]fluorophenyl)-1,3-benzothiazole was synthesized as a fluorine-18 labelled derivative of the Pittsburg Compound-B (PIB), which has known affinity for amyloid beta and promising characteristics as tracer for in vivo visualisation of amyloid deposits in patients suffering from Alzheimer's disease (AD). Both the nitro-precursor 2-(4'-nitrophenyl)-1,3-benzothiazole and the non-radioactive reference compound were synthesized using a 1-step synthesis pathway. Labelling was achieved by direct aromatic nucleophilic substitution of the nitro-precursor using [(18)F]fluoride by heating for 20 min at 150 degrees C and with a radiochemical yield of 38%. The reference compound showed high affinity for amyloid in an in vitro competition binding study using human AD brain homogenates (K(i)=9.0 nM) and fluorescence imaging of incubated transgenic APP mouse brain slices confirmed binding to amyloid plaques. A biodistribution study in normal mice showed a high brain uptake at 2 min pi (3.20%ID/g) followed by a fast washout (60 min pi: 0.21%ID/g). A dynamic microPET study was performed in a transgenic APP and normal WT mouse, but, similar to [(11)C]PIB, no difference was seen in tracer retention between both kind of mice. The new (18)F-labelled 2-phenylbenzothiazole showed excellent preclinical characteristics comparable with those of the (11)C-labelled PIB.
authors.affiliation: Laboratory for Radiopharmacy, K.U.Leuven, Herestraat 49-bus 821, B-3000 Leuven, Belgium. kim.serdons@pharm.kuleuven.be
authors.forename: K
authors.initials: K
authors.lastname: Serdons
authors.forename: T
authors.initials: T
authors.lastname: Verduyckt
authors.forename: D
authors.initials: D
authors.lastname: Vanderghinste
authors.forename: J
authors.initials: J
authors.lastname: Cleynhens
authors.forename: P
authors.initials: P
authors.lastname: Borghgraef
authors.forename: P
authors.initials: P
authors.lastname: Vermaelen
authors.forename: C
authors.initials: C
authors.lastname: Terwinghe
authors.forename: F
authors.initials: F
authors.lastname: Van Leuven
authors.forename: K
authors.initials: K
authors.lastname: Van Laere
authors.forename: H
authors.initials: H
authors.lastname: Kung
authors.forename: G
authors.initials: G
authors.lastname: Bormans
authors.forename: A
authors.initials: A
authors.lastname: Verbruggen
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000682:Amyloid / Q000737:chemistry; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008956:Models, Chemical; D013696:Temperature; D014018:Tissue Distribution
chemical_list: C539872:2-(4'-fluorophenyl)-1,3-benzothiazole; D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D052160:Benzothiazoles; D005462:Fluorine Radioisotopes; C005465:benzothiazole