Flori Alessandra, Liserani Matteo, Frijia Francesca, Giovannetti Giulio, Lionetti Vincenzo, Casieri Valentina, Positano Vincenzo, Aquaro Giovanni Donato, Recchia Fabio A, Santarelli Maria Filomena, Landini Luigi, Ardenkjaer-Larsen Jan Henrik, Menichetti Luca
Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
Department of Physics, University of Pisa, Pisa, Italy.
Contrast Media Mol Imaging. 2015 May-Jun;10(3):194-202. doi: 10.1002/cmmi.1618. Epub 2014 Sep 8.
Dissolution-dynamic nuclear polarization (dissolution-DNP) for magnetic resonance (MR) spectroscopic imaging has recently emerged as a novel technique for noninvasive studies of the metabolic fate of biomolecules in vivo. Since acetate is the most abundant extra- and intracellular short-chain fatty acid, we focused on [1-(13) C]acetate as a promising candidate for a chemical probe to study the myocardial metabolism of a beating heart. The dissolution-DNP procedure of Na[1-(13) C]acetate for in vivo cardiac applications with a 3 T MR scanner was optimized in pigs during bolus injection of doses of up to 3 mmol. The Na[1-(13) C]acetate formulation was characterized by a liquid-state polarization of 14.2% and a T1Eff in vivo of 17.6 ± 1.7 s. In vivo Na[1-(13) C]acetate kinetics displayed a bimodal shape: [1-(13) C]acetyl carnitine (AcC) was detected in a slice covering the cardiac volume, and the signal of (13) C-acetate and (13) C-AcC was modeled using the total area under the curve (AUC) for kinetic analysis. A good correlation was found between the ratio AUC(AcC)/AUC(acetate) and the apparent kinetic constant of metabolic conversion, from [1-(13) C]acetate to [1-(13) C]AcC (kAcC ), divided by the AcC longitudinal relaxation rate (r1 ). Our study proved the feasibility and the limitations of administration of large doses of hyperpolarized [1-(13) C]acetate to study the myocardial conversion of [1-(13) C]acetate in [1-(13) C]acetyl-carnitine generated by acetyltransferase in healthy pigs.
用于磁共振（MR）波谱成像的溶解动态核极化（溶解-DNP）最近已成为一种用于体内生物分子代谢命运无创研究的新技术。由于乙酸盐是细胞外和细胞内最丰富的短链脂肪酸，我们将[1-（13）C]乙酸盐作为研究跳动心脏心肌代谢的化学探针的有前景候选物进行了研究。在猪体内，使用3 T MR扫描仪进行体内心脏应用时，对高达3 mmol剂量的[1-（13）C]乙酸钠的溶解-DNP程序进行了优化。[1-（13）C]乙酸钠制剂的特征在于14.2%的液态极化率和体内17.6±1.7 s的T1Eff。体内[1-（13）C]乙酸钠动力学呈双峰形状：在覆盖心脏体积的切片中检测到[1-（13）C]乙酰肉碱（AcC），并使用曲线下总面积（AUC）对（13）C-乙酸盐和（13）C-AcC的信号进行建模以进行动力学分析。发现AUC（AcC）/AUC（乙酸盐）的比值与代谢转化的表观动力学常数之间具有良好的相关性，该代谢转化是从[1-（13）C]乙酸盐到[1-（13）C]AcC（kAcC），并除以AcC纵向弛豫率（r1）。我们的研究证明了在健康猪中给予大剂量超极化[1-（13）C]乙酸盐以研究由乙酰转移酶产生的[1-（13）C]乙酸盐在[1-（13）C]乙酰肉碱中的心肌转化的可行性和局限性。
