Abstract
11C-acetate is a positron emission tomography (PET) tracer of oxidative metabolism, whereas hyperpolarized 13C-acetate can be used in magnetic resonance imaging (MRI) for investigating specific metabolic processes. The aims of this study were to examine if the kinetic formalism of 11C-acetate PET in the kidneys is comparable to that of 13C-acetate MRI, and to compare the dynamic metabolic information of hyperpolarized 13C-acetate MRI with that obtained with 11C-acetate PET. Rats were examined with dynamic hyperpolarized 13C-acetate MRI or 11C-acetate PET before and after intravenous injection of furosemide, a loop diuretic known to alter both the hemodynamics and oxygen consumption in the kidney. The metabolic clearance rates (MCR) were estimated and compared between the two modalities experimentally in vivo and in simulations. There was a clear dependency on the mean transit time and MCR for both 13C-acetate and 11C-acetate following furosemide administration, while no dependencies on the apparent renal perfusion were observed. This study demonstrated that hyperpolarized 13C-acetate MRI is feasible for measurements of the intrarenal energetic demand via the MCR, and that the quantitative measures are correlated with those measured by 11C-acetate PET, even though the temporal window is more than 30 times longer with 11C-acetate.
Highlights
11C-acetate is a positron emission tomography (PET) tracer of oxidative metabolism, whereas hyperpolarized 13C-acetate can be used in magnetic resonance imaging (MRI) for investigating specific metabolic processes
In order to simulate the in vivo situation, a radiofrequency field (RF) inhomogeneity of 50% and T1 variation of 29% in concern with a noise level of 5% was used to identify the relationship between the actual metabolic clearance rates (MCR) and the proposed formalism derived KMTT (Fig. 1C,D)
The 13C-acetate compartment response was found to correlate well without both relaxation and RF depletion (P < 0.0001, R = 0.99), an offset was observed between the K input in the simulation and the estimated 13C-KMTT
Summary
11C-acetate is a positron emission tomography (PET) tracer of oxidative metabolism, whereas hyperpolarized 13C-acetate can be used in magnetic resonance imaging (MRI) for investigating specific metabolic processes. Rats were examined with dynamic hyperpolarized 13C-acetate MRI or 11C-acetate PET before and after intravenous injection of furosemide, a loop diuretic known to alter both the hemodynamics and oxygen consumption in the kidney. A highly successful clinical metabolic imaging modality, positron emission tomography (PET), relies on the isotopic labeling of biological molecules and allows quantifiable perfusion, uptake, and metabolism[28]. In PET, metabolically active molecules rely solely on signal changes associated with the injected compound to quantify various metabolic alterations in vivo, as opposed to hyperpolarized 13C, where the downstream metabolic conversion is directly detected. Demonstrated to be associated with alterations in oxidative metabolism, is the metabolic clearance rate (MCR) of 11C-acetate PET30,32,33. 11C-acetate will be metabolized via acetyl-CoA synthetase to acetyl-CoA, which enters the tri-carboxylic acid (TCA) cycle, a reaction that has been shown to be proportional to the oxidative rate of the cycle[30]
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