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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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)

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Acknowledgments

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.

Funding

This work was supported by The Ben and Catherine Ivy Foundation (SSG), GE Healthcare (SSG), and Stanford Translational Research and Applied Medicine Fellowship (CB).

Author information

Authors and Affiliations

  1. Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University, Stanford, CA, 94305, USA

    Corinne Beinat, Chirag B. Patel, Tom Haywood, Bin Shen, Harsh Gandhi, Dawn Holley, Mehdi Khalighi & Sanjiv Sam Gambhir

  2. Division of Neuro-Oncology, Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, 94305, USA

    Chirag B. Patel & Lewis Naya

  3. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, School of Medicine, Stanford University, Stanford, CA, 94305, USA

    Andrei Iagaru & Guido Davidzon

  4. Departments of Bioengineering and Materials Science & Engineering, Bio-X, Stanford University, Stanford, CA, 94305, USA

    Sanjiv Sam Gambhir

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  1. Corinne Beinat
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Correspondence to Sanjiv Sam Gambhir.

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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.

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Beinat, C., Patel, C.B., Haywood, T. et al. Human biodistribution and radiation dosimetry of [18F]DASA-23, a PET probe targeting pyruvate kinase M2. Eur J Nucl Med Mol Imaging 47, 2123–2130 (2020). https://doi.org/10.1007/s00259-020-04687-0

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