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

Gandhi, Richa; Cawthorne, Christopher; Craggs, Lucinda J.L.; Wright, John D.; Domarkas, Juozas; He, Ping; Koch-Paszkowski, Joanna; Shires, Michael; Scarsbrook, Andrew F.; Archibald, Stephen J.; Tsoumpas, Charalampos; Bailey, Marc A.

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.

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

• Journal Article Type: Article
• Acceptance Date: Oct 21, 2019
• Online Publication Date: Nov 18, 2019
• Publication Date: Jan 1, 2019
• Deposit Date: Jan 20, 2020
• Publicly Available Date: Jan 21, 2020
• Journal: Journal of Nuclear Cardiology
• Print ISSN: 1071-3581
• Electronic ISSN: 1532-6551
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1007/s12350-019-01946-y
• Keywords: Vascular biology; aneurysms; PET; molecular imaging; vascular imaging; pre-clinical imaging
• Public URL: https://hull-repository.worktribe.com/output/3295558