PT  - JOURNAL ARTICLE
AU  - Bauer, Martin
AU  - Karch, Rudolf
AU  - Tournier, Nicolas
AU  - Cisternino, Salvatore
AU  - Wadsak, Wolfgang
AU  - Hacker, Marcus
AU  - Marhofer, Peter
AU  - Zeitlinger, Markus
AU  - Langer, Oliver
TI  - Assessment of P-Glycoprotein Transport Activity at the Human Blood–Retina Barrier with (<em>R</em>)‐<sup>11</sup>C-Verapamil PET
AID  - 10.2967/jnumed.116.182147
DP  - 2017 Apr 01
TA  - Journal of Nuclear Medicine
PG  - 678--681
VI  - 58
IP  - 4
4099  - http://jnm.snmjournals.org/content/58/4/678.short
4100  - http://jnm.snmjournals.org/content/58/4/678.full
SO  - J Nucl Med2017 Apr 01; 58
AB  - 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)-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 (K1, k2) and total retinal distribution volume VT. Results: During ABCB1 inhibition, retinal VT and influx rate constant K1 were significantly, by 1.4 ± 0.5-fold and 1.5 ± 0.3-fold, increased compared with baseline. Retinal efflux rate constant k2 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.