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

Prof. Daniele Zullino

Status

Not yet enrolling

Conditions

Healthy

Dosimetry

Treatments

Procedure: PBR111 injection

Drug: [18F]PBR111

Device: PET scan

Radiation: PBR111 dosimetry

Study type

Interventional

Funder types

Other

Identifiers

NCT06398392

2022-00542

Details and patient eligibility

About

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.

Full 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.

Enrollment

6 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

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).