Synthesis and Evaluation of 13N-Labelled Azo Compounds for β-Amyloid Imaging in Mice
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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.
Five 13N-labelled azo compounds (1–5) were synthesized using a three-step process using cyclotron-produced [13N]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.
13N-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.
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.
Key wordsPositron emission tomography Tg2576 Alzheimer's disease Nitrogen-13 β-Amyloid Animal biomarker
This work was supported by EU grant PITN-GA-2012-316882 and by intramural FIMA (Fundación para la Investigación Médica Aplicada) funds. We acknowledge Dr. Juan Domingo Gispert for fruitful discussion about experimental design details.
Conflict of interest
None of the authors has any conflict of interest.
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