Objective

Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N-dimethylaminoazobenzene ([(11)C]TAZA), for binding to Aβ plaques in postmortem human brain (AD and normal control (NC)).

Methods

Radiosyntheses of [(11)C]TAZA, related [(11)C]Dalene ((11)C-methylamino-4'-dimethylaminostyrylbenzene), and reference [(11)C]PIB were carried out using [(11)C]methyltriflate prepared from [(11) C]CO(2) and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Aβ plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution.

Results

The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/μmol. TAZA had an affinity, K(i) = 0.84 nM and was five times more potent than PIB. [(11)C]TAZA bound specifically to Aβ plaques present in AD brains with gray matter to white matter ratios >20. [(11)C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11)C]TAZA and [(11)C]PIB. [(11)C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker.

Conclusion

[(11)C]TAZA exhibited high binding to Aβ plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated.