Imaging the Activity of Efflux Transporters at the Blood–Brain Barrier in Neurologic Diseases: Radiotracer Selection Criteria

Efflux transporters of the adenosine triphosphate–binding cassette (ABC) superfamily, such as P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), are highly expressed at the blood–brain barrier (BBB), where they contribute to maintaining brain homeostasis. P-gp may serve as an imaging biomarker to assess the contribution of BBB functionality rather than integrity to the onset or progression of various neurologic diseases. Considerable efforts have been made to develop radiolabeled P-gp substrates to assess cerebral P-gp activity with PET. However, initially developed radiotracers have limited clinical utility as they lack sensitivity to detect moderate, physiologically relevant changes in cerebral P-gp activity. Learning from this molecular imaging area has called for specific criteria, different from those classically used for other central nervous system targets, for developing and selecting suitable PET tracers to study ABC transporter activity at the BBB in different neurologic diseases.