In Vivo Study of Neuroinflammation in Tobaccosmoking: a Clinical PET Study of TSPO Using [18F]PBR111

Healthy Clinical Trial

Official title:

In Vivo Study of Neuroinflammation in Tobaccosmoking: a Clinical Positron EmissionTomography (PET) Study of 18 kDa TranslocatorProtein (TSPO) Using [18F]PBR111 (Part A)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06398392
• Other study ID #: 2022-00542
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 2, 2024
• Est. completion date: May 1, 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Geneva
• Contact: Stergios Tsratsalis, Dr
• Phone: +41 79 5530791
• Email: stergios.tsartsalis[@]hug.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Tobacco smoking is associated with multiple and well-recognized adverse health effects. However, the direct effects of smoking on the brain are less well understood. On of the mechanisms that could be associated with tobacco-related brain toxicity is neuroinflammation. PET/CT imaging constitutes an excellent means of assessment of neuroinflammation in vivo, with the quantification of TSPO using [18F]PBR111. Nonetheless, this radiopharmaceutical has not been authorized for human use in Switzerland.

Description:

Our study thus includes two parts. Part A involves a dosimetry study (i.e. measure the exposure of the body organs of healthy individuals to radioactivity after the administration of 200 MBq of [18F]PBR111. This is a prerequisite for the authorization of the use of this radiotracer in humans. Next, the main part of this study (part B) involves the comparison of the quantity of TSPO in the brain of otherwise healthy smokers and age- and sex-matched non-smokers.

Part A:

Primary objective: to establish the exposure of the organs/tissues to a standard radioactive dose (200 MBq) of [18F]PBR111.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Dosimetry
• Healthy

Intervention

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.

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Prof. Daniele Zullino

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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