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.