Quantification of P-glycoprotein function using [18F]MC225 PET

Neurodegenerative diseases, such as Parkinson’s disease (PD), involve altered mechanisms, and one area of research suggests that P-glycoprotein (P-gp) dysfunction and blood-brain barrier (BBB) disruption may play a role. P-gp, an efflux transporter, regulates drug access to the brain and organs, affecting drug efficacy and resistance. Dysfunctional P-gp may impede the clearance of harmful substances from the brain, allowing toxic compounds to enter the central nervous system.
This PhD thesis advances P-gp quantification methods using [18F]MC225, a P-gp PET tracer, focusing on sex-related differences, applications in neurodegenerative disorders, and alternative tracer administration techniques. To refine these methods, one study explored the estimation of blood time-activity curves without continuous arterial sampling, testing whether venous blood could serve as a substitute for arterial samples. When sex differences were examined, no substantial variations were found between healthy older males and females; however, further studies in younger populations are warranted. In the PD study, no significant differences in brain and small intestine P-gp function compared to healthy controls were observed.
Furthermore, the thesis examined the potential for the oral administration of PET tracers to investigate gastrointestinal absorption and the gut-brain axis. A preclinical study has shown that [18F]MC225 cannot be administered orally at present.
Future research should concentrate on refining imaging techniques to quantify P-gp in the gastrointestinal tract and on addressing motion correction. Investigating the impact of gut microbiota and environmental factors on P-gp function, along with expanding studies on PD, will deepen our understanding of P-gp’s role in health and disease.