RT Journal Article SR Electronic T1 Fetal Imaging of Synaptic Density in the Developing Nonhuman Primate using 11C-UCB-J PET JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 273 OP 273 VO 59 IS supplement 1 A1 Rossano, Samantha A1 Fowles, Krista A1 Holden, Daniel A1 Wilson, Steven A1 Asher, Jennifer A1 Benveniste, Helene A1 Carson, Richard YR 2018 UL http://jnm.snmjournals.org/content/59/supplement_1/273.abstract AB 273Objectives: Synaptogenesis begins halfway through gestation in both nonhuman primates (NHP) and humans. The formation and presence of synapses allows for adequate signaling between neurons, which is critical for proper brain function. Previously, post mortem histological analyses in NHPs have shown changes in synaptic density throughout development. In most brain regions, synaptic density approaches the level of the adult by the end of gestation, continues to increase to almost twice the level of the adult by 4 postnatal months, before a decline and plateau at the adulthood level[1-4]. A limitation to these studies is the cross-sectional design. To limit confounding variables across subjects, a longitudinal measure of synaptic density in development is desirable. The objective of this study is to develop methodology and investigate the efficacy of using 11C-UCB-J PET, which has been used in NHP and humans to estimate synaptic density in vivo, to visualize synaptic vesicle glycoprotein 2A (SV2A) density in the fetal NHP and monitor changes throughout the 165-day gestation period. Methods: Two pregnant rhesus macaques (Macaca mulatta) underwent monthly PET scans with 11C-UCB-J during the final 3 months of gestation, at approximately 80, 110, and 140 post-conception days (pcd). Whole-body dynamic images were acquired on the Siemens Biograph mCT using continuous bed motion. A CT image was taken prior to PET scanning for attenuation correction and anatomical delineation. 11C-UCB-J was administered with a bolus plus constant infusion (B/I) protocol (Kbol = 150), so that equilibrium is reached by ~60 min. No blood samples were acquired. Uptake within the fetal and maternal brain, delineated by the skull on the CT, were quantified as Standardized Uptake Values at equilibrium, and SUV ratios (SUVr) were calculated as fetal/maternal SUV. Relative brain volumes were defined from the CT images. Results: Fetal brain volume increased from 18 mL at 85pcd to about 69 mL (about half the maternal volume) at 140pcd. Using B/I administration, tracer uptake in the maternal and fetal brain equilibrated by 70min postinjection. Within the fetus, most activity localized in the brain, with a smaller amount in the abdomen. SUV and SUVr values are reported in Table 1. SUVr increased from 0.20 at 85pcd to 0.36 at 140pcd. These values are lower than values reported with postmortem NHP studies, in which the fetal synaptic density approaches or reaches 100% of the adult level in the month prior to birth [1]. Within the fetal brain, tracer distribution was nonuniform, with higher midbrain and cerebellar activity compared to the cerebral cortex. These regional differences are consistent with post mortem NHP data, where synaptic density in the visual, prefrontal, and limbic cortices reached 5-8 synapses/100 μm2 neuropil at around 140pcd, while the motor and somatosensory regions reached 10-15 synapses/100 μm2 neuropil at that time[1]. Conclusions: PET imaging with 11C-UCB-J in the pregnant NHP demonstrates tracer increasing and regionally varying uptake in the fetal brain. By 140pcd, fetal brain tracer concentration reaches ~35% of the total maternal brain uptake. Future work is necessary for more accurate quantification of radiotracer distribution, including kinetic modeling with an image derived input function from the maternal blood pool or other fetal regions, partial volume corrections, and corrections for nondisplaceable uptake. View this table:Table 1: SUV and SUVr of Maternal and Fetal Brain Uptake of 11C-UCB-J