[11C]N-desmethyl-loperamide, a substrate that selectively images P-glycoprotein function, is trapped in lysosomes

Introduction: Three efflux transporters of the ATP-binding cassette family block the passage of drugs, or substrates, across the blood–brain barrier: P-glycoprotein (P-gp), multi-drug resistance protein 1 (Mrp1), and breast cancer resistance protein (BCRP). The substrate radiotracer [C]N-desmethyl-loperamide ([C]dLop) has been developed to measure the in vivo activity of these transporters [1–3]. However, two properties of dLop are unknown: 1) its selectivity as a substrate for these three transporters, and 2) its mechanism of unexpected trapping once it enters the brain following P-gp inhibition [1].