A1 Journal article – refereed
Longitudinal Amyloid Imaging in Mouse Brain with C-11-PIB: Comparison of APP23, Tg2576, and APP(swe)-PS1(dE9) Mouse Models of Alzheimer Disease

List of Authors: Snellman A, Lopez-Picon FR, Rokka J, Salmona M, Forloni G, Scheinin M, Solin O, Rinne JO, Haaparanta-Solin M
Publication year: 2013
Journal: Journal of Nuclear Medicine
Journal name in source: JOURNAL OF NUCLEAR MEDICINE
Journal acronym: J NUCL MED
Number in series: 8
Volume number: 54
Issue number: 8
Number of pages: 8
ISSN: 0161-5505

Follow-up of beta-amyloid (A beta) deposition in transgenic mouse models of Alzheimer disease (AD) would be a valuable translational tool in the preclinical evaluation of potential antiamyloid therapies. This study aimed to evaluate the ability of the clinically used PET tracer C-11-Pittsburgh compound B (C-11-PIB) to detect changes over time in A beta deposition in the brains of living mice representing the APP23, Tg2576, and APP(swe)-PS1(dE9) transgenic mouse models of AD. Methods: Mice from each transgenic strain were imaged with 60-min dynamic PET scans at 7-9, 12, 15, and 18-22 mo of age. Regional C-11-PIB retention was quantitated as distribution volume ratios using Logan graphical analysis with cerebellar reference input, as radioactivity uptake ratios between the frontal cortex (FC) and the cerebellum (CB) during the 60-min scan, and as bound-to-free ratios in the late washout phase (40-60 min). Ex vivo autoradiography experiments were performed after the final imaging session to validate C-11-PIB binding to A beta deposits. Additionally, the presence of A beta deposits was evaluated in vitro using staining with thioflavin-S and A beta(1-40), A beta(1-16), and A beta(N3(pE)) immunohistochemistry. Results: Neocortical C-11-PIB retention was markedly increased in old APP23 mice with large thioflavin-S positive All deposits. At 12 mo, the Logan distribution volume ratio for the FC was 1.03 and 0.93 (n = 2), increasing to 1.38 +/- 0.03 (n = 3) and 1.34 (n = 1) at 18 and 21 mo of age, respectively. An increase was also observed in bound-to-free ratios for the FC between young (7- to 12-mo-old) and old (15- to 22-mo-old) APP23 mice. Binding of C-11-PIB to A beta-rich cortical regions was also evident in ex vivo autoradiograms of APP23 brain sections. In contrast, no increases in C-11-PIB retention were observed in aging Tg2576 or APP(swe)-PS1(dE9) mice in vivo, although in the latter, extensive A beta deposition was already observed at 9 mo of age with immunohistochemistry. Conclusion: The results suggest that C-11-PIB binding to A beta deposits in transgenic mouse brain is highly dependent on the AD model and the structure of its A beta plaques. Longitudinal in vivo C-11-PIB uptake studies are possible in APP23 mice.

Last updated on 2019-03-09 at 17:38