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. 2009 May-Jun;16(3):411-21.
doi: 10.1007/s12350-009-9051-7. Epub 2009 Feb 11.

Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate

Zulfia Kisrieva-Ware  1 , Andrew R Coggan, Terry L Sharp, Carmen S Dence, Robert J Gropler, Pilar Herrero
Affiliations

Assessment of myocardial triglyceride oxidation with PET and 11C-palmitate

Zulfia Kisrieva-Ware et al. J Nucl Cardiol. 2009 May-Jun.

Abstract

Background: The goal of this study was to test whether myocardial triglyceride (TG) turnover including oxidation of TG-derived fatty acids (FA) could be assessed with PET and (11)C-palmitate.

Methods and results: A total of 26 dogs were studied fasted (FAST), during Intralipid infusion (IL), during a hyperinsulinemic-euglycemic clamp without (HIEG), or with Intralipid infusion (HIEG + IL). (11)C-palmitate was injected, and 45 minutes were allowed for labeling of myocardial TG pool. 3D PET data were then acquired for 60 minutes, with first 15 minutes at baseline followed by 45 minutes during cardiac work stimulated with constant infusion of either phenylephrine (FAST, n = 6; IL, n = 6; HIEG + IL, n = 6) or dobutamine (FAST, n = 4; HIEG, n = 4). Myocardial (11)C washout during adrenergic stimulation (AS) was fitted to a mono-exponential function (Km(PET)). To determine the source of this (11)C clearance, Km(PET) was compared to direct coronary sinus-arterial measurements of total (11)C activity, (11)C-palmitate, and (11)CO(2). Before AS, PET curves in all groups were flat indicating absence of net clearance of (11)C activity from heart. In both FAST groups, AS resulted in negligible net (11)C activity and (11)CO(2) production higher than net (11)C-palmitate uptake. AS with phenylephrine resulted in net myocardial uptake of total (11)C activity and (11)C-palmitate in IL and HIEG + IL, and (11)CO(2) production lower than (11)C-palmitate uptake. In contrast, AS with dobutamine in HIEG resulted in net clearance of all (11)C metabolites (total (11)C activity, (11)C-palmitate and (11)CO(2)) with (11)CO(2) contributing 66% to endogenous FA oxidation. The AS resulted in significant Km(PET) in all the groups, except HIEG + IL. However, positive correlation between Km(PET) and (11)CO(2) was observed only in HIEG (R (2) = 0.83, P = .09).

Conclusions: This is the first study to demonstrate that using PET and pre-labeling of intracardiac TG pool with (11)C-palmitate, noninvasive assessment of myocardial TG use is feasible under metabolic conditions that favor endogenous TG use such as increased metabolic demand (beta-adrenergic stimulation of cardiac work) with limited availability of exogenous substrate (HIEG).

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Figures

Figure 1
Figure 1
Directly measured averaged coronary sinus - arterial difference (CS-ART) for total 11C activity (black bars), 11C-palmitate (white bars) and 11CO2 (grey bars) before (A and C) and during adrenergic stimulation of cardiac work (B and D) with phenylephrine (A and B) and dobutamine (C and D). Data is presented as group mean ± SD.
Figure 2
Figure 2
Representative myocardial PET time activity curves (dots) and mono-exponential fitting (lines) of total PET 11C activity (y axes) during adrenergic stimulation of cardiac work with phenylephrine (A-C) and dobutamine (D-E). Km - rate of 11C clearance from myocardium.
Figure 3
Figure 3
Correlation between total 11C clearance measured by PET (Km(PET) (y axes) (A-F) and averaged coronary sinus – arterial difference (x axes) of total 11C activity (A and D), 11C-palmitate (B and E), and 11CO2 (C and F) during adrenergic stimulation of cardiac work with dobutamine in FAST (A-C) and HIEG (D-F) studies. Negative values on x-axes indicate tracer uptake and positive values tracer clearance.
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