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. 2015:14:516-25.

Determination of Fatty Acid Metabolism with Dynamic [11C]Palmitate Positron Emission Tomography of Mouse Heart In Vivo

Yinlin Li, Tao Huang, Xinyue Zhang, Min Zhong, Natalie N Walker, Jiang He, Stuart S Berr, Susanna R Keller, Bijoy K Kundu

Determination of Fatty Acid Metabolism with Dynamic [11C]Palmitate Positron Emission Tomography of Mouse Heart In Vivo

Yinlin Li et al. Mol Imaging. 2015.

Abstract

The goal of this study was to establish a quantitative method for measuring fatty acid (FA) metabolism with partial volume (PV) and spill-over (SP) corrections using dynamic [(11)C]palmitate positron emission tomographic (PET) images of mouse heart in vivo. Twenty-minute dynamic [(11)C]palmitate PET scans of four 18- to 20-week-old male C57BL/6 mice under isoflurane anesthesia were performed using a Focus F-120 PET scanner. A model-corrected blood input function, by which the input function with SP and PV corrections and the metabolic rate constants (k1-k5) are simultaneously estimated from the dynamic [(11)C]palmitate PET images of mouse hearts in a four-compartment tracer kinetic model, was used to determine rates of myocardial fatty acid oxidation (MFAO), myocardial FA esterification, myocardial FA use, and myocardial FA uptake. The MFAO thus measured in C57BL/6 mice was 375.03 ± 43.83 nmol/min/g. This compares well to the MFAO measured in perfused working C57BL/6 mouse hearts ex vivo of about 350 nmol/g/min and 400 nmol/min/g. FA metabolism was measured for the first time in mouse heart in vivo using dynamic [(11)C]palmitate PET in a four-compartment tracer kinetic model. MFAO obtained with this model was validated by results previously obtained with mouse hearts ex vivo.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1. Block diagram of the 4-compartment model
Compartment 1 represents the vascular space; 2, the interstitial and intracellular spaces; 3, neutral lipids, amino acids and other slow turnover pools; and 4, mitochondrial β-oxidation. kn represents the forward and backward rate constants between compartments, F is myocardial blood flow, V is fractional vascular volume and Ca(t) is arterial tracer concentration over time.
Figure 2
Figure 2. 11C-palmitate PET images of mouse heart in vivo
(A) Example of a PET image at the last time frame of the dynamic data set. The image also exhibits regions of interest in the left ventricular blood pool and the myocardium. (B) Model fits to the blood and the myocardial time activity curves without interpolation. (C) Cubic spline interpolation resulted in improved fits especially at the peak region for the time activity curve obtained from the LV blood pool.
Figure 3
Figure 3. Model corrected blood input function
The model corrected blood input function (MCIF), Ca(t), computed by simultaneous estimation compared to the image-derived blood input function (IDIF: PET blood) obtained from the dynamic 11C-palmitate PET images. MCIF estimation improved radioactivity recovery at the early time points and eliminated SP contamination at the late time points from the myocardium to the LV blood pool.
Figure 4
Figure 4. FA metabolic parameters in mouse heart in vivo
Myocardial fatty acid oxidation, myocardial fatty acid esterification (MFAE) and myocardial fatty acid utilization (MFAU) computed from dynamic 11C-palmitate PET images of mouse heart in vivo.
See this image and copyright information in PMC

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