Synthesis and evaluation of (13)N-labelled azo compounds for β-amyloid imaging in mice.

Purpose: The aim of the present study was to develop short half-lived tools for in vitro and in vivo β-amyloid imaging in mice, for which no suitable PET tracers are available.

Procedures: Five (13)N-labelled azo compounds (1-5) were synthesized using a three-step process using cyclotron-produced [(13)N]NO3 (-). Biodistribution studies were performed using positron emission tomography-computed tomography (PET-CT) on 20-month-old healthy, wild-type (WT) mice. In vivo and in vitro binding assays were performed using PET-CT and autoradiography, respectively, on 20-month-old healthy (WT) mice and transgenic (Tg2576) Alzheimer's disease model mice.

Results: (13)N-labelled azo compounds were prepared with decay corrected radiochemical yields in the range 27 ± 4 % to 39 ± 4 %. Biodistribution studies showed good blood-brain barrier penetration for compounds 1 and 3-5; good clearance data were also obtained for compounds 1-3 and 5. Compounds 2, 3 and 5 (but not 1) showed a significant uptake in β-amyloid-rich structures when assayed in in vitro autoradiographic studies. PET studies showed significant uptake of compounds 2 and 3 in the cortex of transgenic animals that exhibit β-amyloid deposits.

Conclusions: The results underscore the potential of compounds 2 and 3 as in vitro and in vivo markers for β-amyloid in animal models of Alzheimer's disease.