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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. Methods: We performed PET scans with the ABCB1 substrate ( R )- 11 C-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 ( K  1 , k  2 ) and total retinal distribution volume V  T  Results: During ABCB1 inhibition, retinal V  T and influx rate constant K  1 were significantly, by 1.4 ± 0.5-fold and 1.5 ± 0.3-fold, increased compared with baseline. Retinal efflux rate constant k  2 was significantly decreased by 2.8 ± 1.0-fold. Conclusion: We found a significant increase in ( R )- 11 C-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.

Assessment of P-Glycoprotein Transport Activity at the Human Blood–Retina Barrier with (R)‐11C-Verapamil PET

Assessment of P-Glycoprotein Transport Activity at the Human Blood–Retina Barrier with (R)‐¹¹C-Verapamil PET