TY - JOUR
T1 - Cell proliferation detected using [18F]FLT PET/CT as an early marker of abdominal aortic aneurysm
AU - Gandhi, Richa
AU - Cawthorne, Christopher
AU - Craggs, Lucinda J.L.
AU - Wright, John D.
AU - Domarkas, Juozas
AU - He, Ping
AU - Koch-Paszkowski, Joanna
AU - Shires, Michael
AU - Scarsbrook, Andrew F.
AU - Archibald, Stephen J.
AU - Tsoumpas, Charalampos
AU - Bailey, Marc A.
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - aneurysms
KW - molecular imaging
KW - PET
KW - pre-clinical imaging
KW - Vascular biology
KW - vascular imaging
U2 - 10.1007/s12350-019-01946-y
DO - 10.1007/s12350-019-01946-y
M3 - Article
C2 - 31741324
AN - SCOPUS:85075332298
SN - 1071-3581
VL - 28
SP - 1961
EP - 1971
JO - Journal of Nuclear Cardiology
JF - Journal of Nuclear Cardiology
ER -