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Experimental Genetics Group

Bolleke Abstract   Pijltje
Synthesis of 18F-labelled 2-(4'-fluorophenyl)-1,3-benzothiazole and evaluation as amyloid imaging agent in comparison with [11C]PIB.

Bioorg Med Chem Lett. 2009 Feb 1;19(3):602-5.

Serdons K1*, Verduyckt T1, Vanderghinste D2, Cleynhens J1, Borghgraef P3, Vermaelen P2, Terwinghe C2, Van Leuven F3, Van Laere K2, Kung H4, Bormans G1, Verbruggen A1.

1Laboratory for Radiopharmacy, K.U.Leuven, Leuven, Belgium.
2Nuclear Medicine, U.Z.Gasthuisberg, Leuven, Belgium.
3Laboratory of Experimental Genetics and Transgenesis, K.U.Leuven, Leuven, Belgium.
4Department of Radiology, University of Pennsylvania, Philadelphia, USA.
*Corresponding author.

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.

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