PET/CT imaging of the late-gestation fetal brain in pregnant rats: A proof-of-concept study

Abstract

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 (n = 42 fetuses). [¹⁸F]FDG uptake in rat fetuses was readily visualized by PET imaging. Additionally, in vivo fetal brain [¹⁸F]FDG concentration (standardized uptake value (SUV)) was significantly correlated with ex vivo SUV from matched post-mortem brains (R² = 0.90, p < 0.001). We further investigated the effect of the dopamine receptor antagonist haloperidol on cerebral glucose metabolism (CMR_glu) and [¹¹C]raclopride binding in maternal and fetal brains. Dopamine D2 receptor blockade by haloperidol resulted in significant decreases (p < 0.001, n = 33 vs 9 fetuses) in in vivo CMR_glu and ex vivo [¹⁸F]FDG SUV. Consistently, haloperidol pretreatment significantly decreased [¹¹C]raclopride SUV ratio (SUVR) by 17% (p < 0.001, n = 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.