Radiation Dosimetry of the 18 kDa Translocator Protein Ligand [18F]PBR111 in Humans

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Dosimetry
• Intervention / Treatment: Drug: [18F]PBR111; Procedure: PBR111 injection; Device: PET scan; Radiation: PBR111 dosimetry

Detailed Description

This study investigated the whole-body biodistribution and radiation dosimetry of the second-generation TSPO radioligand [18F]PBR111 in healthy volunteers. The translocator protein (TSPO, 18 kDa) is a mitochondrial marker overexpressed in activated microglia and astrocytes during neuroinflammatory processes such as Alzheimer's disease, multiple sclerosis, and other neurological or systemic conditions. [18F]PBR111, a fluorine-18 labeled imidazopyridine derivative, offers high affinity and specificity for TSPO but is sensitive to the rs6971 polymorphism, leading to different binding classes (high- and mixed-affinity binders). Establishing accurate human dosimetry was essential before extending its clinical use.

Six healthy volunteers (3 females, 3 males) free from chronic or acute inflammatory, infectious, or allergic conditions were recruited under local ethics approval (Geneva University Hospitals). All participants underwent genotyping for the rs6971 polymorphism to confirm the absence of low-affinity binders. Each subject received approximately 200 MBq of [18F]PBR111 intravenously, synthesized via an automated AllInOne module using [18F]fluoride produced on an IBA 18.5 MeV cyclotron. Radiochemical preparation included QMA cartridge trapping, elution with tetrabutylammonium hydroxide, azeotropic drying, nucleophilic substitution with the precursor, purification by semi-preparative HPLC, and formulation through dual C18 SepPak cartridges, ethanol/saline elution, and sterilizing filtration. The final product was obtained with high radiochemical purity and molar activity.

Dynamic whole-body PET/CT was performed on a Siemens Biograph™ Vision 600 Edge using continuous bed motion and 10 sequential passes of increasing duration over ~130 minutes. Low-dose CT provided attenuation correction. PET images were reconstructed with OP-OSEM (2 iterations, 21 subsets), incorporating TOF and resolution modeling, and expressed as SUV (body weight normalized). Organ segmentation was achieved using a deep-learning model applied to PET/CT data, covering major target organs (liver, lungs, spleen, kidneys, red bone marrow, GI tract, urinary bladder, heart wall, pancreas, adrenals, thyroid, etc.), with the remainder of the body included for dosimetric completeness.

Organ time-activity curves were derived from decay-corrected PET data, integrated, and analyzed using OLINDA/EXM v2.2 to calculate residence times and absorbed doses. Effective dose estimates followed ICRP-103 methodology. Statistical analyses included Mann-Whitney tests (sex effects) and Friedman tests with Dunn's multiple comparisons (organ contributions).

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland
    • Geneva University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged ≥18 (3 male and 3 female participants)
• Fluent in French and able and willing to provide written informed consent.

Exclusion Criteria:

• Homozygosity for the rs6971 polymorphism on TSPO that results in low-affinity binding. This criterion is added because this polymorphism alters significantly the ability of the radiotracer [18F]PBR111 to bind to TSPO, hence precluding quantification.
• Absence of a stable contraceptive regimen (specifically, intrauterine contraceptive device or contraceptive treatment per os). Only women with stable contraception will be added to eliminate the risk of exposure of pregnant women and their foetus to radioactivity.
• Presence of any significant history or current diagnosis of chronic disease or syndrome (including neurological, psychiatric, cardiovascular, oncological, metabolic, rheumatological conditions).
• One or more episode(s) of acute infectious or allergic reaction in the last month before inclusion and during the study period. Again, we cannot exclude that such conditions might produce immune alterations in the brain, thus confounding the results of TSPO quantification with [18F]PBR111.
• Presence of clinically relevant laboratory abnormalities in the haematological and biochemical blood tests, as defined as laboratory values that require clinical workup and/or treatment (e.g. anaemia, hyperglycaemia, electrolyte imbalances)
• A body mass index <20 or >30 (this criterion is necessary because TSPO has been shown to be variable with respect to body mass index (113-115)).
• Exposure to research related radiation in the past five years that, when combined with this study, would place subjects above the allowable limits.
• Conditions precluding entry into the scanners (e.g. claustrophobia).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Drug: radiation dosimetry and biodistribution; 6 healthy adult volunteers (3 men and 3 women) will be assigned to the radiation dosimetry group. [18F]PBR111 will be administered once.

Drug: [18F]PBR111; [18F]PBR111 is a radiotracer produced at University Hospital of Geneva in a radiopharmaceutical GMP facility. The drug product is provided as sterile solution for intravenous injection in a glass vial containing 10 mL (max) of formulated product, the maximal applicable dose being 200 MBq.; Other Names: Preparation; Procedure: PBR111 injection; [18F]PBR111 will be administered once, intravenously in the antecubital fossa at a dose of 200 MBq; Device: PET scan; Upon administration of the radiotracer, a 120-minute PET/CT scan will be initiated.; Radiation: PBR111 dosimetry; to establish the exposure of the organs/tissues to a standard radioactive dose (200 MBq) of [18F]PBR111

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of radiation dosimetry and biodistribution of the translocator protein radiotracer [18F]PBR111 determined with PET/CT in healthy human volunteers (3 male and 3 female participants)	[18F]PBR111 will be manually injected as a smooth bolus followed by a 20-ml saline flush via an intravenous catheter in the antecubital fossa placed before the scan. After injecting a standard [18F]PBR111 activity of 200 MBq, PET/CT scans will be performed on a BiographTM mCT or Vision scanner (Siemens Healthcare, Erlangen, Germany). The whole duration of the scanning protocol is about 120 minutes, consisting of CT and PET dynamic acquisitions.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculation of the total radiation exposure of a PET/CT with 200 MBq of [18F]PBR111	ROIs will be delineated manually using the Osirix software on a number of internal organs directly on the PET images with the help of the CT scan for radiation dosimetry calculations. The selected ROIs will be whole brain, left and right lung and kidney, liver, heart wall, spleen, bladder, bone marrow and organs displaying an activity concentration above background. The delineated ROIs will then be copied on all dynamic PET series to extract the time activity curves (TACs) for each organ/tissue. The total number of disintegrations (formerly referred to as residence times) will be extracted and used as input to the OLINDA/EXM software to estimate the radiation dose to organs and the effective dose to the reference adult male from mimicking the adult subjects enrolled in the study protocol.	6 months

Collaborators and Investigators

• Sponsor: Prof. Daniele Zullino

Publications and helpful links

General Publications

• Tournier BB, Mansouri Z, Salimi Y, Ceyzeriat K, Mathoux G, Richard-Lepouriel H, Zullino D, Bois F, Zaidi H, Garibotto V, Tsartsalis S, Millet P. 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2024
• Primary Completion (Actual): July 30, 2024
• Study Completion (Actual): July 30, 2024

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: May 2, 2024
• First Posted (Actual): May 3, 2024

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Inflammation; Neuroinflammatory Diseases; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Image Interpretation, Computer-Assisted; Image Enhancement; Photography; Tomography, Emission-Computed; Radionuclide Imaging; Diagnostic Techniques, Radioisotope; Positron-Emission Tomography; 2-(6-chloro-2-(4-(3-fluoropropoxy)phenyl)imidazo(1,2-a)pyridin-3-yl)-N,N-diethylacetamide
• Other Study ID Numbers: 2022-00542

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No