Human biodistribution and radiation dosimetry of [F]DASA-23, a PET probe targeting pyruvate kinase M2.

Purpose: To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([F]DASA-23) in healthy volunteers.

Methods: We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software.

Results: All subjects tolerated the PET/MRI examination, without adverse reactions to [F]DASA-23. [F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [F]DASA-23 was 23.5 ± 5.8 μSv/MBq.

Conclusion: We successfully completed a pilot first-in-human study of [F]DASA-23. Our results indicate that [F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [F]DASA-23 to visualize intracranial malignancies, NCT03539731.

Trial Registration: ClinicalTrials.gov , NCT03539731 (registered 28 May 2018).