Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2

• Published in: European journal of nuclear medicine and molecular imaging Vol. 47; no. 9; pp. 2123 - 2130
• Main Authors: Beinat, Corinne, Patel, Chirag B., Haywood, Tom, Shen, Bin, Naya, Lewis, Gandhi, Harsh, Holley, Dawn, Khalighi, Mehdi, Iagaru, Andrei, Davidzon, Guido, Gambhir, Sanjiv Sam
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2020; Springer Nature B.V
• Subjects: Blood-brain barrier; Cardiology; Diazonium Compounds; Dosimeters; Dosimetry; Emission analysis; Evaluation; Fluorine isotopes; Gallbladder; Humans; Imaging; Informed consent; Injection; Intestine; Magnetic resonance imaging; Medicine; Medicine & Public Health; Nuclear Medicine; Oncology; Organs; Original Article; Orthopedics; Pharmaceuticals; Piperazine; Positron emission; Positron emission tomography; Pyruvate kinase; Pyruvate Kinase - metabolism; Pyruvic acid; Radioactive tracers; Radiochemistry; Radioisotopes; Radiology; Radiometry; Small intestine; Sulfanilic Acids; Tissue Distribution; Tomography; F]DASA-23; Radiation dosimetry; [; PKM2; Biodistribution; First-in-human; [18F]DASA-23
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-020-04687-0

Purpose To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[ 18 F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([ 18 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 [ 18 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 [ 18 F]DASA-23. [ 18 F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [ 18 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 [ 18 F]DASA-23 was 23.5 ± 5.8 μSv/MBq. Conclusion We successfully completed a pilot first-in-human study of [ 18 F]DASA-23. Our results indicate that [ 18 F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [ 18 F]DASA-23 to visualize intracranial malignancies, NCT03539731. Trial registration ClinicalTrials.gov , NCT03539731 (registered 28 May 2018)