Positron emission tomography-based radiopharmaceuticals for imaging the expression and function of multidrug resistance P-glycoprotein.

Multidrug resistance is a major reason for drug resistance in patients undergoing chemotherapy or other drug therapy. The overexpression of efflux proteins, such as multidrug resistance protein or P-glycoprotein (P-gp), has been recognized as a major cause of the drugs' efflux from the brain. P-gp expression is not only responsible for drug resistance, but underactivity leads to the accumulation of amyloid proteins and may become one of the reasons for Alzheimer disease. Hence, measuring the activity of the efflux proteins can indicate whether the candidate is suitable for chemotherapy. Therefore, several radiotracers have been developed to image P-gp activity. Positron emission tomography imaging can assess P-gp function and, therefore, plays a crucial role in informing clinicians' decisions to adjust treatment. This review article discusses advancements in radiopharmaceuticals for imaging P-gp function and expression, particularly at the blood-brain barrier. It highlights the significance of various radiolabeled tracers, including verapamil, metoclopramide, and MC225, in assessing P-gp-mediated drug delivery to the brain and its role in various neurodisorders. This article discusses the outcomes of various radiopharmaceuticals used in imaging P-gp expression and function. SIGNIFICANCE STATEMENT: This review article highlights the evolution of radiopharmaceuticals for imaging P-gp in various disorders, including drug resistance, Alzheimer disease, and epilepsy. P-gp imaging can play a crucial role in drug development and aid in identifying tumors that are responsive or resistant to chemotherapy. It may help clinicians decide whether a patient is suitable for chemotherapy. Positron emission tomography imaging can provide information on P-gp activity, which can be assessed before and during chemotherapy.