Monitoring the Function of the P-glycoprotein Transporter at the Blood Brain Barrier

The P-glycoprotein (P-gp) transporter located at the blood-brain barrier (BBB) is an efflux transporter that pumps neurotoxic compounds out of the brain. Its main function is to protect the brain to ensure an appropriate neural function. Decreases in the P-gp function can result in increased accumulation of toxic compounds inside the brain such as beta-amyloid and this may cause the development of Alzheimer´s or other neurological disorders. By contrast, increases in the P-gp function can decrease the therapeutic drug concentration inside the brain and influence the efficacy of the treatment (drug resistance) as occurred in patients with intractable epilepsy. Thus, it is of interest to monitor the P-gp function in vivo to facilitate the early diagnosis of brain disorders and to monitor drug resistance. To this aim, we used Positron Emission Tomography (PET) imaging, a non-invasive technique that allows the quantification of biological processes in vivo, and the novel radiotracer [18F]MC225 which measures the P-gp function. The aim was to study the kinetic properties of the radiotracer in different species and prove its efficacy to measure increases and decrease in the P-gp function before its clinical evaluation. We conclude that the obtained results have broadened the knowledge of the P-gp function at the BBB. Moreover, the results highlight that [18F]MC225 may become the first radiofluorinated P-gp PET tracer able to measure both decreases and increases in the P-gp function in vivo. The radiolabeling with fluorine-18 would allow its distribution to other PET centers and improve the image quality.