Human Adult and Adolescent Whole-body Dosimetry of Synaptic Vesicle Glycoprotein 2A Radioligand 11C-UCB-J

1636 Objectives: The synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J has been evaluated in rhesus monkeys,1 baboons2 and human studies2,3 and has demonstrated excellent kinetic properties as a positron emission tomography (PET) radioligand for measuring synaptic density with great potential clinical utility in neuropsychiatric disorders. The ability to scan adolescents, as well as adults, to gain further understanding in vivo of disease progression possibly related to synaptic pruning and density in diseases such as schizophrenia and autism is an important potential application of this tracer. In this study, we performed dynamic whole body scans in young adults and used dosimetry calculations in adult and adolescent phantoms to provide dose estimations of both populations. Methods: Four subjects (2F/2M, 21-30 y) underwent PET/CT imaging after injection of 11C-UCB-J. Mean injected activity was 234±121 MBq and mean injected mass was 0.024±0.019 µg/kg. Subjects were scanned for 1 h with continuous bed motion passes starting with 4x1min then 2x2min and 11x5min passes on a PET/CT scanner. Regions-of-interest (ROI) were drawn manually for the brain, heart, stomach, kidneys, liver, pancreas and spleen on a summed 0-10 min PET image. ROIs for the gallbladder, lungs, urinary bladder and intestines were drawn on a summed 0-30 min PET image. All ROIs were applied to the dynamic PET images to generate time-activity-curves (TACs). Decay correction was removed from the TACs and the area under the curve was calculated for each ROI, extrapolating to infinity using the isotope decay constant. These values were normalized by either the standard 55kg female or 70kg male with appropriate organ size estimations and converted to residence times for each ROI (organ). OLINDA was then used to determine the total dose in each organ, effective dose equivalent and effective dose (mSV/MBq) for each standard OLINDA model: 55kg female, 70kg male and 15-year-old adolescent. Results: Visual evaluation of dosimetry scans detected very high early uptake in the liver and brain (0-10min) (Fig1A). Uptake at 30-60min occurred in the kidneys and urinary bladder, with high radioactivity levels remaining in the brain and liver (Fig 1B). Absorbed doses derived from the 70-kg reference male and 55-kg adult female phantoms are shown in Table 1. Absorbed doses derived from the 15-year-old male and female phantoms are shown in Table 2. The brain is the dose-limiting organ for adults, with a single-study dose limit of 2,908 MBq (78.6 mCi) for a male and 2,105 MBq (56.9 mCi) for female. The lower intestine is the dose-limiting organ in adolescent females, while the bladder is the dose limiting organ in adolescent males (Table 2). According to CFR 361.1, which requires 1/10th of the adult dose for pediatric scans, this produces a single-study dose limit of 229 MBq (6.2mCi) for a male and 225 MBq (6.1 mCi) for females. Conclusions: We have provided dosimetry estimates for adult and adolescent populations showing that this tracer could be used for the study of neuropsychiatric disorders related to synaptic density with 11C-UCB-J in both populations. Based on the high brain SUV in adults (peak of ~ 10), these doses should be more than sufficient for a high-quality scan.REFERENCES: 1. Nabeel, N, et al, JNM 57(5): 777-785 (2016) 2. Finnema, SJ, Sci Transl Med 8 (348): 348ra96 (2016) 3. Finnema, SJ, JCBFM, 38: 2041-2052 (2018)