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 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 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).


CONCLUSIONS
MBF can be quantified by PET using (15)O-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.
Herrero
Pilar
P
Division of Radiological Sciences, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. herrerop@mir.wustl.edu
Kim
Joonyoung
J
Sharp
Terry L
TL
Engelbach
John A
JA
Lewis
Jason S
JS
Gropler
Robert J
RJ
Welch
Michael J
MJ
D000085:Acetates / Q000493:pharmacokinetics; D000818:Animals; D001783:Blood Flow Velocity / Q000502:physiology*; D002244:Carbon / Q000493:pharmacokinetics; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000502:physiology*; D005240:Feasibility Studies; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D010104:Oxygen Radioisotopes / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods / Q000662:veterinary*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014867:Water / Q000378:metabolism
D000085:Acetates; D010104:Oxygen Radioisotopes; D019275:Radiopharmaceuticals; C438206:carbon-11 acetate; D014867:Water; D002244:Carbon