The aim of this study was to investigate whether compartmental modeling of 1-11C-glucose PET kinetics can be used for noninvasive measurements of myocardial glucose metabolism beyond its initial extraction. Methods: 1- 11C-Glucose and U-13C-glucose were injected simultaneously into 22 mongrel dogs under a wide range of metabolic states; this was followed by 1 h of PET data acquisition. Heart tissue samples were analyzed for 13C-glycogen content (nmol/g). Arterial and coronary sinus blood samples (ART/CS) were analyzed for glucose (μmol/mL), 11C-glucose, 11CO2, and 11C-total acidic metabolites ( 11C-lactate [LA] + 11CO2) (counts/min/mL) and were used to calculate myocardial fractions of (a) glucose and 1- 11C-glucose extractions, EF(GLU) and EF(11C-GLU); (b) 11C-GLU and 11C-LA oxidation, OF(11C-GLU) and OF(11C-LA); (c) 11C-glycolsysis, GCF(11C-GLU); and (d) 11C-glycogen content, GNF(11C-GLU). On the basis of these measurements, a compartmental model (M) that accounts for the contribution of exogenous 11C-LA to myocardial 11C activity was implemented to measure M-EF(GLU), M-GCF(GLU), M-OF(GLU), M-GNF(GLU), and the fraction of myocardial glucose stored as glycogen M-GNF(GLU)/M-EF(GLU)). Results: ART/CS data showed the following: (a) A strong correlation was found between EF(11C-GLU) and EF(GLU) (r = 0.92, P < 0.0001; slope = 0.95, P = not significantly different from 1). (b) In interventions with high glucose extraction and oxidation, the contribution of OF(11C-GLU) to total oxidation was higher than that of OF( 11C-LA) (P < 0.01). In contrast, in interventions in which glucose uptake and oxidation were inhibited, OF(11C-LA) was higher than OF(11C-GLU) (P < 0.05). (c) A strong correlation was found between GNF(11C-GLU)/EF(GLU) and direct measurements of fractional 13C-glycogen content, (r = 0.96, P < 0.0001). Model-derived PET measurements of M-EF(GLU), M-GCF(GLU), and M-OF(GLU) strongly correlated with EF(GLU) (slope = 0.92, r = 0.95, P < 0.0001), GCF(11C-GLU) (slope = 0.79, r = 0.97, P < 0.0001), and OF(11C-GLU) (slope = 0.70, r = 0.96, P < 0.0001), respectively. M-GNF(GLU)/M-EF(GLU) strongly correlated with fractional 13C-content (r = 0.92, P < 0.0001). Conclusion: Under nonischemic conditions, it is feasible to measure myocardial glucose metabolism noninvasively beyond its initial extraction with PET using 1- 11C-glucose and a compartmental modeling approach that takes into account uptake and oxidation of secondarily labeled exogenous 11C-lactate.
- Kinetic modeling
- Myocardial glucose metabolism