L-3-11C-lactate as a PET tracer of myocardial lactate metabolism: A feasibility study

Pilar Herrero, Carmen S. Dence, Andrew R. Coggan, Zulfia Kisrieva-Ware, Paul Eisenbeis, Robert J. Gropler

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30 Scopus citations

Abstract

Lactate is a key myocardial energy source. Lactate metabolism is altered in a variety of conditions, such as exercise and diabetes mellitus. However, to our knowledge, noninvasive quantitative measurements of myocardial lactate metabolism have never been performed because of the lack of an adequate radiotracer. In this study we tested L-3-11C-lactate ( 11C-lactate) as such a tracer. Methods: Twenty-three dogs were studied under a wide range of metabolic interventions. 11C-Lactate and 13C-lactate were injected as boluses and PET data were acquired for 1 h. Concomitant arterial and coronary sinus (ART/CS) blood samples were collected to identify 13C-lactate metabolites and to measure fractional myocardial extraction/production of 11C metabolite fractions (11C acidic: 11CO2 and 11C-lactate; 11C basic: 11C-labeled amino acids; and 11C neutral: 11C-glucose). Lactate metabolism was quantified using 2 PET approaches: monoexponential clearance analysis (oxidation only) and kinetic modeling of PET 11C-myocardial curves. Results: Arterial 11C acidic, neutral, and basicmetabolites were identified as primarily 11C-labeled lactate + pyruvate, glucose, and alanine, respectively. Despite a significant contribution of 11C-glucose (23%-45%) and 11C-alanine (<11%) to total arterial 11C activity, both were minimally extracted (+)/produced(-) by the heart (1.7% ± 1.0% and -0.12% ± 0.84%, respectively). Whereas extraction of 11C-lactate correlated nonlinearly with that of unlabeled lactate extraction (r = 0.86, P < 0.0001), 11CO 2 production correlated linearly with extraction of unlabeled lactate (r = 0.89, P < 0.0001, slope = 1.20 ± 0.13). In studies with physiologic free fatty acids (FFA) (415 ± 216 nmol/mL), 11C-lactate was highly extracted (32% ± 12%) and oxidized (26% ± 14%), and PET monoexponential clearance and kinetic modeling analyses resulted in accurate estimates of lactate oxidation and metabolism. In contrast, supraphysiologic levels of plasma FFA (4,111 ± 1,709 nmol/mL) led to poor PET estimates of lactate metabolism due to negligible lactate oxidation (1% ± 2%) and complete backdiffusion of unmetabolized 11C-lactate into the vasculature (28% ± 22%). Conclusion: Under conditions of net lactate extraction, L-3-11C-lactate faithfully traces myocardial metabolism of exogenous lactate. Furthermore, in physiologic substrate environments, noninvasive measurements of lactate metabolism are feasible with PET using myocardial clearance analysis (oxidation) or compartmental modeling. Thus, L-3-11C-lactate should prove quite useful in widening our understanding of the role that lactate oxidation plays in the heart and other tissues and organs.

Original languageEnglish
Pages (from-to)2046-2055
Number of pages10
JournalJournal of Nuclear Medicine
Volume48
Issue number12
DOIs
StatePublished - Dec 1 2007

Keywords

  • Kinetic modeling
  • L-3-C-lactate
  • Myocardial lactate oxidation
  • PET

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