In Vivo Study of Neuroinflammation in Tobaccosmoking: a Clinical PET Study of TSPO Using [18F]PBR111
- Conditions
- DosimetryHealthy
- Interventions
- Drug: [18F]PBR111Procedure: PBR111 injectionDevice: PET scanRadiation: PBR111 dosimetry
- Registration Number
- NCT06398392
- Lead Sponsor
- Prof. Daniele Zullino
- Brief 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.
- Detailed 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 & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 6
- Aged ≥18 (3 male and 3 female participants)
- Fluent in French and able and willing to provide written informed consent.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Drug: radiation dosimetry and biodistribution [18F]PBR111 6 healthy adult volunteers (3 men and 3 women) will be assigned to the radiation dosimetry group. \[18F\]PBR111 will be administered once. Drug: radiation dosimetry and biodistribution PBR111 injection 6 healthy adult volunteers (3 men and 3 women) will be assigned to the radiation dosimetry group. \[18F\]PBR111 will be administered once. Drug: radiation dosimetry and biodistribution PET scan 6 healthy adult volunteers (3 men and 3 women) will be assigned to the radiation dosimetry group. \[18F\]PBR111 will be administered once. Drug: radiation dosimetry and biodistribution PBR111 dosimetry 6 healthy adult volunteers (3 men and 3 women) will be assigned to the radiation dosimetry group. \[18F\]PBR111 will be administered once.
- Primary Outcome Measures
Name Time Method 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) 6 months \[18F\]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.
- Secondary Outcome Measures
Name Time Method Calculation of the total radiation exposure of a PET/CT with 200 MBq of [18F]PBR111 6 months 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.