Radiation dosimetry of the 18 kDa translocator protein ligand [18F]PBR111 in humans

Benjamin B Tournier; Zahra Mansouri; Yazdan Salimi; Kelly Ceyzériat; Gregory Mathoux; Hélène Richard-Lepouriel; Daniele Zullino; Frédéric Bois; Habib Zaidi; Valentina Garibotto; Stergios Tsartsalis; Philippe Millet

doi:10.1016/j.nucmedbio.2025.109011

Radiation dosimetry of the 18 kDa translocator protein ligand [¹⁸F]PBR111 in humans

Nucl Med Biol. 2025 May-Jun:144-145:109011. doi: 10.1016/j.nucmedbio.2025.109011. Epub 2025 Mar 29.

Affiliations

¹ Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.
² Diagnostic Department, Division of Nuclear Medicine and Molecular Imaging, University Hospitals of Geneva, Geneva, Switzerland.
³ CIBM Center for Biomedical Imaging, Geneva, Switzerland.
⁴ Department of Psychiatry, Mood and Anxiety Disorders Unit, University Hospitals of Geneva, Geneva, Switzerland.
⁵ Faculty of Medicine, University of Geneva, Geneva, Switzerland; University Hospitals of Geneva, Geneva, Switzerland.
⁶ Faculty of Medicine, University of Geneva, Geneva, Switzerland; Diagnostic Department, Division of Nuclear Medicine and Molecular Imaging, University Hospitals of Geneva, Geneva, Switzerland.
⁷ Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, Mood and Anxiety Disorders Unit, University Hospitals of Geneva, Geneva, Switzerland.
⁸ Faculty of Medicine, University of Geneva, Geneva, Switzerland; Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. Electronic address: philippe.millet@hcuge.ch.

PMID: 40179687
DOI: 10.1016/j.nucmedbio.2025.109011

Abstract

Purpose: The 18 kDa translocator protein (TSPO) is a mitochondrial protein that becomes overexpressed during neuroinflammatory conditions, such as in Alzheimer's disease or multiple sclerosis. TSPO is of interest because it serves as a marker for microglial and astrocytic activity, measurable via in vivo positron emission tomography (PET) molecular imaging. [¹⁸F]PBR111 is a second-generation TSPO PET radioligand with high signal specificity but a sensitivity to TSPO polymorphism, in comparison with first-generation ligands. This study focused on the biodistribution and dosimetry of [¹⁸F]PBR111 in healthy humans.

Method: Six volunteers (three males, three females) were administered approximately 200 MBq of [¹⁸F]PBR111. Organs such as the lungs and liver showed the highest initial radioactivity level, while the bone marrow and bladder accumulated activity over time, likely reflecting ligand defluorination and elimination.

Results: Dosimetry findings revealed a total effective dose of 16.17 μSv/MBq, equivalent to 3.04 mSv per examination. Compared to animal models, human dosimetry showed lower radiation exposure, highlighting discrepancies in predictive models. Organ-specific dose comparisons with other TSPO ligands ([¹⁸F]PBR06, [¹⁸F]FEPPA, [¹⁸F]FEDAA1106) revealed similar distribution patterns. This study underscores the clinical viability of [¹⁸F]PBR111 for TSPO imaging, providing critical data for optimizing its safe use in research and clinical settings.

Conclusion: The findings support its potential for studying neuroinflammatory and systemic diseases. The trial registration number is NCT06398392.

Keywords: PBR; Radiation dose; TSPO.

Publication types

Clinical Trial

MeSH terms

Adult
Female
Fluorine Radioisotopes*
Humans
Ligands
Male
Middle Aged
Positron-Emission Tomography
Pyridines* / pharmacokinetics
Radiometry*
Receptors, GABA* / metabolism
Tissue Distribution

Substances

Fluorine Radioisotopes
Ligands
Pyridines
Receptors, GABA
TSPO protein, human

Associated data

ClinicalTrials.gov/NCT06398392