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Synthesis and Evaluation of 18F-Labeled 2-Phenylbenzothiazoles as Positron Emission Tomography Imaging Agents for Amyloid Plaques in Alzheimer’s Disease

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posted on 12.03.2009, 00:00 by Kim Serdons, Christelle Terwinghe, Peter Vermaelen, Koen Van Laere, Hank Kung, Luc Mortelmans, Guy Bormans, Alfons Verbruggen
Imaging agents targeting amyloid β (Aβ) may be useful for early diagnosis and follow-up of treatment of patients with Alzheimer’s disease (AD). Three of five tested 2-(4′-fluorophenyl)-1,3-benzothiazoles displayed high binding affinities for Aβ plaques in AD human brain homogenates (Ki between 2.2 and 22.5 nM). They all contained the 18F-label directly attached to the aromatic ring and were synthesized starting from the nitro precursor. Determination of the partition coefficient, biodistribution studies in normal mice, and in vivo μPET studies in normal rats showed that their initial brain uptake was high and brain washout was fast. The most promising compound [18F]5, or 6-methyl-2-(4′-[18F]fluorophenyl)-1,3-benzothiazole, seemed to be metabolically stable in the brain, and its plasma radiometabolites, which do not cross the blood−brain barrier, were determined. The preliminary results strongly suggest that this new fluorinated compound is a promising candidate as an Aβ plaque imaging agent for the study of patients with AD.

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