PET imaging of ABC transporters at the blood-brain barrier

The function of ATP-binding cassette (ABC) transporters at the blood-brain barrier (BBB) is to protect the brain from toxic compounds. Additionally, they play a crucial role in the onset and progression of several central nervous system (CNS) diseases as well as in drug resistance. Many compounds were identified as substrates, inhibitors, inducers, or activators for ABC transporters, causing important drug-drug interactions. PET imaging represents an excellent tool for assessing the function and expression of ABC transporters. Over the last years, many PET tracers with different characteristics have been developed, mainly for measuring P-glycoprotein (P-gp) function at the BBB. Although (R)-[11C]verapamil or [11C]N-desmethylloperamide are considered as the "gold standard" P-gp tracers, they have several drawbacks such as its high affinity to P-gp which limits its use for assessing P-gp increased function. Therefore, PET tracers with lower affinity to the transporter have been developed and studied in different species. The assessment of ABC transporters by PET imaging can provide new insight into the physiology and pathophysiology of different CNS diseases and may open new avenues for therapies. Moreover, PET can be used for screening the affinity of new entities toward various ABC transporters and thus enhance the development of CNS drugs.