Richa Gandhi1,2, Christopher Cawthorne3,4, Lucinda J L Craggs1, John D Wright1,5, Juozas Domarkas3, Ping He3, Joanna Koch-Paszkowski1,5, Michael Shires6, Andrew F Scarsbrook6, Stephen J Archibald3, Charalampos Tsoumpas7,8,9, Marc A Bailey1,10. 1. Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, 8.49c Worsley Building, Clarendon Way, Leeds, LS2 9NL, United Kingdom. 2. Institute of Medical and Biological Engineering, School of Mechanical Engineering, University of Leeds, Leeds, United Kingdom. 3. Department of Biomedical Science, PET Research Centre, University of Hull, Hull, United Kingdom. 4. Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium. 5. Experimental & PreClinical Imaging Facility (ePIC), School of Medicine, University of Leeds, Leeds, United Kingdom. 6. Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom. 7. Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine, University of Leeds, 8.49c Worsley Building, Clarendon Way, Leeds, LS2 9NL, United Kingdom. c.tsoumpas@leeds.ac.uk. 8. Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. c.tsoumpas@leeds.ac.uk. 9. Invicro, London, United Kingdom. c.tsoumpas@leeds.ac.uk. 10. The Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds, United Kingdom.
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 ([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.
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.
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