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Journal of Nuclear Medicine Vol. 47 No. 3 477-485
© 2006 by Society of Nuclear Medicine


Basic Science Investigation

Assessment of Myocardial Blood Flow Using 15O-Water and 1-11C-Acetate in Rats with Small-Animal PET

Pilar Herrero, MS, Joonyoung Kim, PhD, Terry L. Sharp, RT(R), John A. Engelbach, Jason S. Lewis, PhD, Robert J. Gropler, MD and Michael J. Welch, PhD

Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri

Correspondence: For correspondence contact: Pilar Herrero, MS, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8225, 510 S. Kingshighway Blvd., St. Louis, MO 63110. E-mail: herrerop{at}mir.wustl.edu

This feasibility study was undertaken to determine whether myocardial blood flow (MBF, mL/g/min) could be quantified noninvasively 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 FBM (spillover correction) after fixing FMM (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.

Key Words: small-animal PET • myocardial blood flow • 15O-water • 1-11C-acetate


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