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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

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 kinetic modeling in conjunction with small-animal PET could noninvasively quantify alterations in myocardial perfusion and substrate metabolism in rats. Methods: All small-animal PET was performed on either of 2 tomographs. Myocardial blood flow and substrate metabolism were measured in 10 male Zucker diabetic fatty rats (ZDF, fa/fa) and 10 lean littermates (Lean, Fa/+) using ¹⁵O-water, 1-¹¹C-glucose, 1-¹¹C-acetate, and 1-¹¹C-palmitate. Animals were 12.0 ± 1.4-wk old. Results: Consistent with a type 2 diabetic phenotype, the ZDF animals showed higher plasma hemoglobin A_1c, insulin, glucose, and free fatty acid (FFA) levels than their lean controls. Myocardial glucose uptake (mL/g/min) was not significantly different between the 2 groups. However, higher glucose plasma levels in the ZDF rats resulted in higher myocardial glucose utilization (nmol/g/min) (Lean, 629 ± 785, vs. ZDF, 1,737 ± 1,406; P = 0.06). Similarly, myocardial FFA uptake (mL/g/min) was not significantly different between the 2 groups, (Lean, 0.51 ± 28, vs. ZDF, 0.72 ± 0.19; P = not significant) However, due to higher FFA plasma levels, utilization and oxidation (nmol/g/min) were significantly higher in the ZDF group (Lean, 519 ± 462, vs. ZDF, 1,623 ± 712, P < .001; and Lean, 453 ± 478, vs. ZDF, 1,636 ± 730, P < .01). Conclusion: Noninvasive measurements of myocardial substrate metabolism in ZDF rats using small-animal PET are consistent with the expected early metabolic abnormalities that occur in this well-characterized model of type 2 diabetes mellitus. Thus, small-animal PET demonstrates significant promise in providing a means to link the myocardial metabolic abnormalities that occur in rat of disease with the human condition.

Key Words: metabolism • diabetes mellitus • fatty acids • imaging • PET

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