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Assessment of Myocardial Metabolism in Diabetic Rats Using Small-Animal PET: A Feasibility Study

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

View larger version (10K): [in a new window]   FIGURE 1.  PET protocol for GAP studies. Blood sampling was performed throughout the study to determine substrate/insulin plasma levels (6 samples, 5–25 µL) and labeled blood metabolites (15 samples, 5 µL; 11C-CO2 for 1-11C-acetate and 1-11C-palmitate and 11C-CO2/11C-lactate for 1-11C-glucose). MBF = myocardial blood flow; MVO2 = myocardial oxygen consumption; MGU = myocardial glucose utilization; MFAU = myocardial fatty acid utilization; MFAO = myocardial fatty acid oxidation; MFAO/MFAU = myocardial FFA that is oxidized.

View larger version (25K): [in a new window]   FIGURE 2.  Myocardial PET images from a ZDF rat (A) and its lean mate (B) undergoing a GAP study. Images generated by summing data acquired from 0 to 2 min after tracer injection and representing primarily myocardial tracer uptake are shown in transaxial short-axis view. When compared with images from lean control rat, higher glucose and free fatty acid (FFA) accumulation observed in ZDF rat is indicative of higher glucose (1,607 vs. 2,256 nmol/g/min) and FFA utilization (429 vs. 1,394 nmol/g/min). Within the first 2 min after tracer injection, blood 1-11C-acetate time–activity curve showed faster clearance than blood 1-11C-palmitate time–activity curve, resulting in a sharper myocardial 1-11C-acetate image.

View larger version (17K): [in a new window]   FIGURE 3.  Compartmental model representing myocardial 1-11C-glucose kinetics. Ca(t) = blood 1-11C-glucose activity over time (input function, cpm/mL); K1 (mL/g/min) and k2–k5 (min–1) = transfer rate constants; qn (cpm/mL) = concentration of tracer in compartment n; MBF (mL/g/min) = MBF measured from kinetics of 15O-water; V (mL/g) = myocardial fractional vascular volume (assumed to be 10% of total myocardial volume).

View larger version (13K): [in a new window]   FIGURE 4.  Glucose metabolism measurements obtained in ZDF and lean rats by compartmental modeling of 1-11C-glucose PET data. MGUP = myocardial glucose uptake; MGU = myocardial glucose utilization. *P < 0.0001; **P = 0.06 (, ZDF; , Lean).

View larger version (20K): [in a new window]   FIGURE 5.  FFA metabolism measurements obtained in ZDF and lean rats by compartmental modeling of 1-11C-palmitate PET data. MFAUP = myocardial fatty acid uptake; MFAU = myocardial fatty acid utilization; MFAO = myocardial fatty acid oxidation; MFAO/MFAU = myocardial FFA that was oxidized. *P < 0.001; **P < 0.01 (, ZDF; , Lean).