Assessment of myocardial blood flow using ¹⁵O-water and 1- ¹¹C-acetate in rats with small-animal PET

This feasibility study was undertaken to determine whether myocardial blood flow (MBF, mL/g/min) could be quantified non-invasively in small rodents using microPET and ¹⁵O-water or 1-¹¹C-acetate. Methods: MBF was measured in 18 healthy rats using PET and ¹⁵O-water (MBF-W) under different interventions and compared with direct measurements obtained with microspheres (MBF-M). Subsequently, MBF was estimated in 24 rats at rest using 1-¹¹C-acetate (MBF-Ace) and compared with measurements obtained with ¹⁵O-water. Using factor analysis, images were processed to obtain 1 blood and 1 myocardial time-activity curve per tracer per study. MBF-W was calculated using a well-validated 1-compartment kinetic model. MBF-Ace was estimated using a simple 1-compartment model to estimate net tracer uptake, K₁ (K₁ (mL/g/min) = MBF·E; E = first-pass myocardial extraction of 1-¹¹C-acetate) and washout (k₂ (min^-1)) along with F_BM (spillover correction) after fixing F_MM (partial-volume correction) to values obtained from ¹⁵O-water modeling. K₁ values were converted to MBF values using a first-pass myocardial extraction/flow relationship measured in rats (E = 1.0-0.74·exp(-1.13/MBF)). Results: In the first study, MBF-W correlated well with MBF-M (y = 0.74x + 0.96; n = 18, r = 0.91, P < 0.0001). However, the slope was different than unity, P < 0.05). Refitting of the data after forcing the intercept to be zero resulted in a nonbias correlation between MBF-W and MBF-M (y = 0.95x + 0.0; n = 18, r = 0.86, P < 0.0001) demonstrating that the underestimation of the slope could be attributed to the overestimation of MBF-W for 2 MBF-M values lower than 1.50 mL/g/min. In the second study, MBF-Ace values correlated well with MBF-W with no underestimation of MBF (y = 0.91x + 0.35; n = 24, r = 0.87, P < 0.0001). Conclusion: MBF can be quantified by PET using ¹⁵O-water or 1-¹¹C-acetate in healthy rats. Future studies are needed to determine the accuracy of the methods in low-flow states and to develop an approach for a partial-volume correction when 1- ¹¹C-acetate is used.