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

IF 3.6 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2025-03-29 DOI:10.1016/j.nucmedbio.2025.109011

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

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引用次数: 0

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.

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来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

期刊介绍： Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized. These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field. Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.