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

作者：Bauer Martin; Karch Rudolf; Tournier Nicolas; Cisternino Salvatore; Wadsak Wolfgang; Hacker Marcus; Marhofer Peter; Zeitlinger Markus; Langer Oliver^*

来源：Journal of Nuclear Medicine, 2017, 58(4): 678-681.

DOI：10.2967/jnumed.116.182147

• eye
• blood-retina barrier
• blood-brain barrier
• P-glycoprotein
• PET

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)-C-11-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 VT 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)-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.

• 出版日期2017-4
• 单位中国地震局