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Cell proliferation detected using [18F]FLT PET/CT as an early marker of abdominal aortic aneurysm

Abstract

© 2019, The Author(s). Background: Abdominal aortic aneurysm (AAA) is a focal aortic dilatation progressing towards rupture. Non-invasive AAA-associated cell proliferation biomarkers are not yet established. We investigated the feasibility of the cell proliferation radiotracer, fluorine-18-fluorothymidine ([18F]FLT) with positron emission tomography/computed tomography (PET/CT) in a progressive pre-clinical AAA model (angiotensin II, AngII infusion). Methods and Results: Fourteen-week-old apolipoprotein E-knockout (ApoE−/−) mice received saline or AngII via osmotic mini-pumps for 14 (n = 7 and 5, respectively) or 28 (n = 3 and 4, respectively) days and underwent 90-minute dynamic [18F]FLT PET/CT. Organs were harvested from independent cohorts for gamma counting, ultrasound scanning, and western blotting. [18F]FLT uptake was significantly greater in 14- (n = 5) and 28-day (n = 3) AAA than in saline control aortae (n = 5) (P < 0.001), which reduced between days 14 and 28. Whole-organ gamma counting confirmed greater [18F]FLT uptake in 14-day AAA (n = 9) compared to saline-infused aortae (n = 4) (P < 0.05), correlating positively with aortic volume (r = 0.71, P < 0.01). Fourteen-day AAA tissue showed increased expression of thymidine kinase-1, equilibrative nucleoside transporter (ENT)-1, ENT-2, concentrative nucleoside transporter (CNT)-1, and CNT-3 than 28-day AAA and saline control tissues (n = 3 each) (all P < 0.001). Conclusions: [18F]FLT uptake is increased during the active growth phase of the AAA model compared to saline control mice and late-stage AAA.

Journal Article Type Article
Publication Date Jan 1, 2019
Journal Journal of Nuclear Cardiology
Print ISSN 1071-3581
Electronic ISSN 1532-6551
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
APA6 Citation Gandhi, R., Cawthorne, C., Craggs, L. J., Wright, J. D., Domarkas, J., He, P., …Bailey, M. A. (2019). Cell proliferation detected using [18F]FLT PET/CT as an early marker of abdominal aortic aneurysm. Journal of Nuclear Cardiology, https://doi.org/10.1007/s12350-019-01946-y
DOI https://doi.org/10.1007/s12350-019-01946-y
Keywords Vascular biology; aneurysms; PET; molecular imaging; vascular imaging; pre-clinical imaging

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