Abstract
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Objectives Clinical PET radiotracers including 15O-water, 13N-ammonia, 62Cu-PTSM and 82Rb are used to assess renal blood flow (RBF). 11C-acetate has been proposed as a myocardial flow tracer, but has not been evaluated for RBF in small animals. Absolute RBF is important in assessing new therapies for transgenic hypertensive and diabetic mouse models of disease. This study evaluates RBF repeatability in control and hypertensive mice with 11C-acetate micro-PET.
Methods Healthy control (CTRL) C57BL mice (N=10) and endothelial nitric oxide synthase knockout (eNOS-KO) mice (N=5) were IV-injected with 33 ± 8 MBq of 11C-acetate using a micro-volumetric syringe pump (75μL in 45s). List-mode (20 min) micro-PET acquisitions were performed at baseline (test) and follow-up (retest) within 2 weeks, with physiological monitoring of hemodynamics and respiration. A one-tissue-compartment model with image-derived input function from the inferior vena cava was used to estimate the uptake (K1 mL/min/g) and clearance (k2 /min) rates as indices of RBF and myocardial oxygen consumption (MVO2).
Results eNOS-KO mice showed a decrease in heart rate (16%), increase in respiratory rate (70%) and elevated blood pressure (20%) vs. CTRL. Mean RBF values tended to be higher in the eNOS-KO mice 2.6±0.7 mL/min/g vs. CTRL 2.1±0.7 mL/min/g (p=0.07). Test-retest repeatability was similar between groups, assessed by the coefficients of repeatability (CR): 2.0 vs. 1.7 mL/min/g (p=0.60), with no mean difference between test and retest RBF. Mean MVO2 was significantly higher in eNOS-KO mice 0.8±0.1 /min vs. CTRL 0.6±0.2 /min (p=0.02). Repeatability was equivalent for both groups (CR=0.5 /min), again with no mean difference between test and retest MVO2.
Conclusions RBF and MVO2 can be assessed with good repeatability in healthy control mice and in a hypertensive mouse model of vascular disease. 11C-acetate shows high potential as a PET radiotracer to quantify renal perfusion and oxidative metabolism in mouse models of health and disease.