Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2
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To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[18F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in healthy volunteers.
We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [18F]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.
All subjects tolerated the PET/MRI examination, without adverse reactions to [18F]DASA-23. [18F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [18F]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 [18F]DASA-23 was 23.5 ± 5.8 μSv/MBq.
We successfully completed a pilot first-in-human study of [18F]DASA-23. Our results indicate that [18F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [18F]DASA-23 to visualize intracranial malignancies, NCT03539731.
ClinicalTrials.gov, NCT03539731 (registered 28 May 2018)
Keywords[18F]DASA-23 PKM2 First-in-human Radiation dosimetry Biodistribution
We thank the Cyclotron and Radiochemistry Facility at Stanford for their support in particular Dr. Fred Chin, Jun Hyung Park, Jessa B. Castillo, and Carmen Azevedo. We would also like to thank Geoffrey Warnock from PMOD Technologies LLC and Stanford Division of Neuro-oncology in particular Drs. Lawrence Recht, Seema Nagpal, Reena Thomas, Priya Yerraballa, Sophie Bertrand, and Mark Santos. CB acknowledges receipt of a Stanford Translational Research and Applied Medicine fellowship.
This work was supported by The Ben and Catherine Ivy Foundation (SSG), GE Healthcare (SSG), and Stanford Translational Research and Applied Medicine Fellowship (CB).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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