Ignite Creation Date:
2025-12-24 @ 3:30 PM
Ignite Modification Date:
2025-12-27 @ 6:41 PM
Study NCT ID:
NCT06398392
Status:
COMPLETED
Last Update Posted:
2025-09-16
First Post:
2024-04-23
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Radiation Dosimetry of the 18 kDa Translocator Protein Ligand [18F]PBR111 in Humans
Sponsor:
Prof. Daniele Zullino
Organization:
Study Overview
Official Title:
Radiation Dosimetry of the 18 kDa Translocator Protein Ligand [18F]PBR111 in Humans
Status:
COMPLETED
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
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).
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: