Pearson Torben D, Bricault Sarah, Yoo Chi-Hyeon, Wey Hsiao-Ying
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
McLean Imaging Center, McLean Hospital, Belmont, MA, USA.
J Cereb Blood Flow Metab. 2025 Sep 8:271678X251370861. doi: 10.1177/0271678X251370861.
Preclinical PET studies offer the opportunity to elucidate molecular mechanisms underlying early neurodevelopment with minimal invasiveness. We demonstrated the feasibility of fetal brain PET in four pregnant rats ( = 42 fetuses). [F]FDG uptake in rat fetuses was readily visualized by PET imaging. Additionally, in vivo fetal brain [F]FDG concentration (standardized uptake value (SUV)) was significantly correlated with ex vivo SUV from matched post-mortem brains ( = 0.90, < 0.001). We further investigated the effect of the dopamine receptor antagonist haloperidol on cerebral glucose metabolism (CMR) and [C]raclopride binding in maternal and fetal brains. Dopamine D2 receptor blockade by haloperidol resulted in significant decreases ( < 0.001, = 33 vs 9 fetuses) in in vivo CMR and ex vivo [F]FDG SUV. Consistently, haloperidol pretreatment significantly decreased [C]raclopride SUV ratio (SUVR) by 17% ( < 0.001, = 6 vs 6 fetuses) in the fetal whole-brain, using the maternal cerebellum as the reference region. In all, our results show that PET/CT imaging of the fetal rat brain can reliably quantify specific molecular targets in vivo, and future translational studies of neurodevelopment are feasible in this model.
临床前正电子发射断层扫描(PET)研究提供了以最小的侵入性阐明早期神经发育潜在分子机制的机会。我们在4只怀孕大鼠(共42只胎儿)中证明了胎儿脑PET的可行性。通过PET成像可以很容易地观察到大鼠胎儿体内[F]氟代脱氧葡萄糖(FDG)的摄取情况。此外,胎儿脑内[F]FDG浓度(标准化摄取值(SUV))与配对的死后大脑的离体SUV显著相关(r = 0.90,P < 0.001)。我们进一步研究了多巴胺受体拮抗剂氟哌啶醇对母体和胎儿大脑中脑葡萄糖代谢(CMR)和[C]雷氯必利结合的影响。氟哌啶醇对多巴胺D2受体的阻断导致体内CMR和离体[F]FDG SUV显著降低(P < 0.001,分别为33只与9只胎儿)。同样,以母体小脑作为参考区域,氟哌啶醇预处理使胎儿全脑中[C]雷氯必利SUV比值(SUVR)显著降低了17%(P < 0.001,分别为6只与6只胎儿)。总之,我们的结果表明,胎鼠脑PET/CT成像能够可靠地在体内定量特定分子靶点,并且在该模型中进行未来神经发育的转化研究是可行的。