Assessment of P-Glycoprotein Transport Activity at the Human Blood-Retina Barrier with (<i>R</i>)-¹¹C-Verapamil PET.

Abstract

P-glycoprotein (ABCB1) is expressed at the blood-retina barrier (BRB), where it may control distribution of drugs from blood to the retina and thereby influence drug efficacy and toxicity. <b>Methods:</b> We performed PET scans with the ABCB1 substrate (<i>R</i>)-¹¹C-verapamil on 5 healthy male volunteers without and with concurrent infusion of the ABCB1 inhibitor tariquidar. We estimated the rate constants for radiotracer transfer across the BRB (<i>K</i>₁, <i>k</i>₂) and total retinal distribution volume <i>V</i>_T<b>Results:</b> During ABCB1 inhibition, retinal <i>V</i>_T and influx rate constant <i>K</i>₁ were significantly, by 1.4 ± 0.5-fold and 1.5 ± 0.3-fold, increased compared with baseline. Retinal efflux rate constant <i>k</i>₂ was significantly decreased by 2.8 ± 1.0-fold. <b>Conclusion:</b> We found a significant increase in (<i>R</i>)-¹¹C-verapamil distribution to the retina during ABCB1 inhibition, which provides first in vivo evidence for ABCB1 transport activity at the human BRB. The increase in retinal distribution was approximately 2.5-fold less pronounced than previously reported for the blood-brain barrier.