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

• DOI: 10.1007/s12350-019-01946-y
• Publication Date: 2019-11-18T22:01:31Z
• Authors: Richa Gandhi; Christopher Cawth...; Lucinda J.L. Craggs; John D. Wright; Juozas Domarkas; Ping He; Joanna Koch-Paszk...; Michael Shires; Andrew F. Scarsbrook; Stephen J. Archibald; Charalampos Tsoumpas; Marc A. Bailey
• Keywords: Male; Fluorine Radioisotopes; Mice, Knockout, ApoE; Angiotensin II; 610; molecular imaging; Vascular biology; Dideoxynucleosides; 3. Good health; Disease Models, Animal; Mice; 03 medical and health sciences; PET; aneurysms; 0302 clinical medicine; pre-clinical imaging; vascular imaging; Positron Emission Tomography Computed Tomography; Animals; Original Article; Aortic Aneurysm, Abdominal; Cell Proliferation

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).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).[18F]FLT uptake is increased during the active growth phase of the AAA model compared to saline control mice and late-stage AAA.