Jiang Donglang, Lu Xiuhong, Li Zijing, Rydberg Nicklas, Zuo Chuantao, Peng Fangyu, Hua Fengchun, Guan Yihui, Xie Fang
PET Center, Huashan Hospital, Fudan University, Shanghai, China.
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, China.
Front Neurosci. 2019 Jan 15;12:1052. doi: 10.3389/fnins.2018.01052. eCollection 2018.
Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT. A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats ( = 6) post sequential intravenous injection of F-PF-(+)-DTBZ, C-CFT, and F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum). Variable uptake of F-PF-(+)-DTBZ and C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of F-PF-(+)-DTBZ and C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively). Age-dependent increases of striatal of F-FDG, F-PF-(+)-DTBZ, and C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation.
青少年大脑的发育和成熟是一个复杂的过程，其代谢和神经传递途径会发生积极变化。正电子发射断层扫描（PET）是一种用于追踪青少年大脑代谢和功能变化的有用成像方式。在本研究中，使用PET/CT研究了大鼠青少年大脑发育过程中葡萄糖代谢、囊泡单胺转运体2和多巴胺转运体的表达变化。对一组Wistar大鼠（n = 6）分别序贯静脉注射F-PF-(+)-DTBZ、C-CFT和F-FDG后，进行了关于青少年大脑中VMAT2、DAT和葡萄糖代谢随年龄变化的纵向PET/CT研究。在2、4、9和12月龄时进行PET采集。对包括纹状体、小脑和海马体在内的不同脑区的放射性示踪剂摄取进行定量，并记录为标准化摄取值（SUV）和纹状体特异性摄取率（SUVR：脑区SUV/小脑SUV）。检测到F-PF-(+)-DTBZ和C-CFT的摄取存在变化，纹状体和伏隔核中的摄取水平最高。从2月龄（SUV分别为：1.36 ± 0.22、1.37 ± 0.39）到4月龄（SUV分别为：2.22 ± 0.29、2.04 ± 0.33）、9月龄（1.98 ± 0.34、2.09 ± 0.18）、12月龄（SUV分别为：1.93 ± 0.19、2.00 ± 0.17），纹状体中F-PF-(+)-DTBZ和C-CFT的摄取随年龄显著增加，F-FDG的SUV也从2月龄到更大年龄增加（纹状体中SUV：2月龄时为3.71 ± 0.78，4、9、12月龄时分别为5.28 ± 0.81、5.14 ± 0.73、4.94 ± 0.50）。在2至4月龄的大鼠中检测到纹状体中F-FDG、F-PF-(+)-DTBZ和C-CFT摄取随年龄增加，表明纹状体发育在出生后的前4个月出现。4月龄可被视为开展脑部疾病研究以排除持续组织发育干扰的安全阈值。这些发现支持进一步研究DAT、VMAT2表达和葡萄糖代谢随年龄的变化，以探讨它们作为研究大脑发育和功能成熟的新型成像生物标志物的潜在用途。
