Abstract
The purpose of this study was to assess safety, biodistribution, and radiation dosimetry in humans for the highly selective σ-1 receptor PET agent (18)F-6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ((18)F-FTC-146). Methods: Ten healthy volunteers (5 women, 5 men; age ± SD, 34.3 ± 6.5 y) were recruited, and written informed consent was obtained from all participants. Series of whole-body PET/MRI examinations were acquired for up to 3 h after injection (357.2 ± 48.8 MBq). Blood samples were collected, and standard vital signs (heart rate, pulse oximetry, and body temperature) were monitored at regular intervals. Regions of interest were delineated, time-activity curves were calculated, and organ uptake and dosimetry were estimated. Results: All subjects tolerated the PET/MRI examination well, and no adverse reactions to (18)F-FTC-146 were reported. High accumulation of (18)F-FTC-146 was observed in σ-1 receptor-dense organs such as the pancreas and spleen, moderate uptake in the brain and myocardium, and low uptake in bone and muscle. High uptake was also observed in the kidneys and bladder, indicating renal tracer clearance. The effective dose of (18)F-FTC-146 was 0.0259 ± 0.0034 mSv/MBq (range, 0.0215-0.0301 mSv/MBq). Conclusion: First-in-human studies with clinical-grade (18)F-FTC-146 were successful. Injection of (18)F-FTC-146 is safe, and absorbed doses are acceptable. The potential of (18)F-FTC-146 as an imaging agent for a variety of neuroinflammatory diseases is currently under investigation.