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

Corinne Beinat; Chirag B Patel; Tom Haywood; Bin Shen; Lewis Naya; Harsh Gandhi; Dawn Holley; Mehdi Khalighi; Andrei Iagaru; Guido Davidzon; Sanjiv Sam Gambhir

doi:10.1007/s00259-020-04687-0

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

Eur J Nucl Med Mol Imaging. 2020 Aug;47(9):2123-2130. doi: 10.1007/s00259-020-04687-0. Epub 2020 Jan 15.

Authors

Corinne Beinat¹, Chirag B Patel^{1

2}, Tom Haywood¹, Bin Shen¹, Lewis Naya², Harsh Gandhi¹, Dawn Holley¹, Mehdi Khalighi¹, Andrei Iagaru³, Guido Davidzon³, Sanjiv Sam Gambhir^{4

5}

Affiliations

¹ Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
² Division of Neuro-Oncology, Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
³ Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
⁴ Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University, Stanford, CA, 94305, USA. sgambhir@stanford.edu.
⁵ Departments of Bioengineering and Materials Science & Engineering, Bio-X, Stanford University, Stanford, CA, 94305, USA. sgambhir@stanford.edu.

PMID: 31938892
DOI: 10.1007/s00259-020-04687-0

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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

Keywords: Biodistribution; First-in-human; PKM2; Radiation dosimetry; [18F]DASA-23.

Publication types

Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Diazonium Compounds
Humans
Positron-Emission Tomography*
Pyruvate Kinase* / metabolism
Radiometry
Sulfanilic Acids
Tissue Distribution

Substances

Diazonium Compounds
Sulfanilic Acids
Pyruvate Kinase
diazobenzenesulfonic acid

Associated data

ClinicalTrials.gov/NCT03539731