Buschiazzo Ambra, Cossu Vanessa, Bauckneht Matteo, Orengo Annamaria, Piccioli Patrizia, Emionite Laura, Bianchi Giovanna, Grillo Federica, Rocchi Anna, Di Giulio Francesco, Fiz Francesco, Raffaghello Lizzia, Nobili Flavio, Bruno Silvia, Caviglia Giacomo, Ravera Silvia, Benfenati Fabio, Piana Michele, Morbelli Silvia, Sambuceti Gianmario, Marini Cecilia
Department of Health Science, Nuclear Medicine Unit, University of Genoa, Genoa, Italy.
Nuclear Medicine Unit, Polyclinic San Martino Hospital, Largo R. Benzi 10, 16132, Genoa, Italy.
EJNMMI Res. 2018 Jun 11;8(1):44. doi: 10.1186/s13550-018-0398-0.
The close connection between neuronal activity and glucose consumption accounts for the clinical value of 18F-fluoro-2-deoxyglucose (FDG) imaging in neurodegenerative disorders. Nevertheless, brain metabolic response to starvation (STS) might hamper the diagnostic accuracy of FDG PET/CT when the cognitive impairment results in a severe food deprivation.
Thirty six-week-old BALB/c female mice were divided into two groups: "control" group (n = 15) were kept under standard conditions and exposed to fasting for 6 h before the study; the remaining "STS" mice were submitted to 48 h STS (absence of food and free access to water) before imaging. In each group, nine mice were submitted to dynamic micro-PET imaging to estimate brain and skeletal muscle glucose consumption (C- and SM-MRGlu*) by Patlak approach, while six mice were sacrificed for ex vivo determination of the lumped constant, defined as the ratio between CMRGlu* and glucose consumption measured by glucose removal from the incubation medium (n = 3) or biochemical analyses (n = 3), respectively.
CMRGlu* was lower in starved than in control mice (46.1 ± 23.3 vs 119.5 ± 40.2 nmol × min × g, respectively, p < 0.001). Ex vivo evaluation documented a remarkable stability of lumped constant as documented by the stability of GLUT expression, G6Pase activity, and kinetic features of hexokinase-catalyzed phosphorylation. However, brain SUV in STS mice was even (though not significantly) higher with respect to control mice. Conversely, a marked decrease in both SM-MRGlu* and SM-SUV was documented in STS mice with respect to controls.
STS markedly decreases brain glucose consumption without altering measured FDG SUV in mouse experimental models. This apparent paradox does not reflect any change in lumped constant. Rather, it might be explained by the metabolic response of the whole body: the decrease in FDG sequestration by the skeletal muscle is as profound as to prolong tracer persistence in the bloodstream and thus its availability for brain uptake.
神经元活动与葡萄糖消耗之间的紧密联系解释了18F-氟代脱氧葡萄糖（FDG）成像在神经退行性疾病中的临床价值。然而，当认知障碍导致严重食物缺乏时，大脑对饥饿（STS）的代谢反应可能会妨碍FDG PET/CT的诊断准确性。
将36只六周龄的雌性BALB/c小鼠分为两组：“对照组”（n = 15）在标准条件下饲养，并在研究前禁食6小时；其余的“STS”小鼠在成像前接受48小时的STS（无食物，可自由饮水）。每组中，9只小鼠接受动态微型PET成像，通过Patlak方法估计脑和骨骼肌的葡萄糖消耗（C-和SM-MRGlu*），而处死6只小鼠用于离体测定集总常数，集总常数定义为CMRGlu*与通过从孵育培养基中去除葡萄糖（n = 3）或生化分析（n = 3）测量的葡萄糖消耗之间的比率。
饥饿小鼠的CMRGlu低于对照小鼠（分别为46.1±23.3与119.5±40.2 nmol×min×g，p < 0.001）。离体评估表明集总常数具有显著稳定性，这通过GLUT表达、G6Pase活性以及己糖激酶催化磷酸化的动力学特征的稳定性得到证明。然而，STS小鼠的脑SUV相对于对照小鼠甚至（尽管不显著）更高。相反，与对照组相比，STS小鼠的SM-MRGlu和SM-SUV均显著降低。
在小鼠实验模型中，STS显著降低脑葡萄糖消耗，而不改变测量的FDG SUV。这种明显的矛盾并不反映集总常数的任何变化。相反，它可能由全身的代谢反应来解释：骨骼肌对FDG摄取的减少程度之深，以至于延长了示踪剂在血液中的持续时间，从而增加了其被脑摄取的可用性。
