Radiosynthesis and evaluation of [11C]BTA-1 and [11C]3'-Me-BTA-1 as potential radiotracers for in vivo imaging of β-amyloid plaques

Aim: To evaluate the in vitro and in vivo characteristics of [N-methyl-11C]2-(4'-(methylaminophenyl)-benzothiazole ([11C]BTA-1) as well as [N-methyl-11C]2-(3'-methyl- 4'-(methylamino)phenyl)-benzothiazole ([11C]3'-Me- BTA-1) as diagnostic markers of amyloid-β (Aβ) in Alzheimer's disease (AD). Material, methods: Brain uptake and clearance was determined in wild-type mice. Binding affinities (Ki) of [11C]BTA-1 and [11C]3'-Me-BTA-1 for aggregated Aβ(1-40) fibrils were assessed. Autoradiography was performed on brain sections of AD patients. To demonstrate binding specificity in vivo BTA-1 was injected i.p. in transgenic mice (Tg2576). Brain sections were analysed consecutively. Additionally, a [11C]BTA-1 PET study of an AD patient and a healthy control was performed. Results: In mice brain uptake and clearance of [11C]BTA-1 is compatible with the half life of 11C (2 min: 12.7 % ID/g; 30 min: 4.6% ID/g). In contrast clearance rate of [11C]3'-Me- BTA-1 is too slow (2 min 4% ID/g; 30 min 12% ID/g) to achieve sufficient clearance of free and non specifically bound radioactivity. Ki of [11C]BTA-1 is 11 nmol/l and that of [11C]3'-Me-BTA-1 27 nmol/l. Both radioligands label Aβ selectively and specifically in AD patients and transgenic mice in vitro. The in vivo stained brain sections show a labelling of Aβ plaques. The AD patient has a higher prefrontal, parietal and striatal [11C]BTA-1 accumulation than the healthy control. Metabolite analysis revealed approximately 75% intact [11C]BTA-1 after 30min in plasma.[ 11C]BTA-1 is favourable for in vivo imaging of Aβ due to its rapid brain entry, sufficient clearance and good binding affinity for Aβ. Conclusion: The ability to label Aβ plaques in vivo in human subjects supports the suitability of [11C]BTA-1 as a plaque imaging agent.