Blocking of efflux transporters in rats improves translational validation of brain radioligands.

ABSTRACT:

Background

Positron emission tomography (PET) is a molecular imaging technique that can be used to investigate the in vivo pharmacology of drugs. Initial preclinical evaluation of PET tracers is often conducted in rodents due to the accessibility of disease models as well as economic considerations. Compared to larger species, rodents display a higher expression and/or activity of efflux transporters such as the P-glycoprotein (P-gp). Low brain uptake could, therefore, be species-specific and uptake in rodents not be predictive for that in humans. We hypothesized that a better prediction from rodent data could be achieved when a tracer is evaluated under P-gp inhibition. Consequently, we compared the performance of eight neuroreceptor tracers in rats with and without P-gp inhibitio

SUBMITTER: Shalgunov V 

PROVIDER: S-EPMC7572968 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature