1. Cell proliferation detected using [ 18 F]FLT PET/CT as an early marker of abdominal aortic aneurysm.
- Author
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Gandhi R, Cawthorne C, Craggs LJL, Wright JD, Domarkas J, He P, Koch-Paszkowski J, Shires M, Scarsbrook AF, Archibald SJ, Tsoumpas C, and Bailey MA
- Subjects
- Angiotensin II, Animals, Aortic Aneurysm, Abdominal metabolism, Disease Models, Animal, Male, Mice, Mice, Knockout, ApoE, Aortic Aneurysm, Abdominal diagnostic imaging, Aortic Aneurysm, Abdominal pathology, Cell Proliferation, Dideoxynucleosides pharmacokinetics, Fluorine Radioisotopes pharmacokinetics, Positron Emission Tomography Computed Tomography
- Abstract
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 ([
18 F]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 [18 F]FLT PET/CT. Organs were harvested from independent cohorts for gamma counting, ultrasound scanning, and western blotting. [18 F]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 [18 F]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: [18 F]FLT uptake is increased during the active growth phase of the AAA model compared to saline control mice and late-stage AAA., (© 2019. The Author(s).)- Published
- 2021
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