Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP

Purpose [ 18 F]3F4AP is a novel PET radiotracer that targets voltage-gated potassium (K + ) channels and has shown promise for imaging demyelinated lesions in animal models of neurological diseases. This study aimed to evaluate the biodistribution, safety and radiation dosimetry of [ 18 F]3F4AP in healthy human volunteers. Methods Four healthy volunteers (2 female) underwent a 4-hour dynamic PET scan from cranial vertex to mid-thigh using multiple bed positions after administration of 368 ± 17.9 MBq (9.94 ± 0.48 mCi) of [ 18 F]3F4AP was produced in a cGMP laboratory under IND authorization from the FDA. Volumes of interest for relevant organs were manually drawn guided by the CT and PET images and time-activity curves (TACs) were extracted. Radiation dosimetry was estimated from the integrated TACs using OLINDA software. Safety assessments included measuring vital signs immediately before and after the scan, monitoring for adverse events, as well as obtaining a comprehensive metabolic panel (CMP) and electrocardiogram (ECG) within 30 days before and after the scan. The study was approved by the institutional review board (IRB) and registered at clinicaltrials.gov ( NCT04710550 ) before commencement. Results [ 18 F]3F4AP distributed throughout the body with the highest levels of activity in the kidneys, urinary bladder, stomach, liver, spleen and brain and with low accumulation in muscle and fat. The tracer cleared quickly from circulation and from most organs. The clearance of the tracer was noticeably faster than previously reported clearance in nonhuman primates (NHPs). The average effective dose (ED) across all subjects was 12.1 ± 2.2 µSv/MBq, which is lower than the estimated ED from the NHP studies (21.6 ± 0.6 µSv/MBq) as well as the ED of other fluorine-18 radiotracers such as [ 18 F]FDG (∼20 µSv/MBq). No differences in ED between males and females were observed. No substantial changes in safety assessments or adverse events were recorded. Conclusion The biodistribution and radiation dosimetry of [ 18 F]3F4AP in humans is reported for the first time. The average total ED across four subjects was lower than most 18 F-labeled PET tracers. The tracer and study procedures were well tolerated and no adverse events occurred.