RT Journal Article
SR Electronic
T1 Assessment of P-Glycoprotein Transport Activity at the Human Blood–Retina Barrier with (<em>R</em>)‐<sup>11</sup>C-Verapamil PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 678
OP 681
DO 10.2967/jnumed.116.182147
VO 58
IS 4
A1 Bauer, Martin
A1 Karch, Rudolf
A1 Tournier, Nicolas
A1 Cisternino, Salvatore
A1 Wadsak, Wolfgang
A1 Hacker, Marcus
A1 Marhofer, Peter
A1 Zeitlinger, Markus
A1 Langer, Oliver
YR 2017
UL http://jnm.snmjournals.org/content/58/4/678.abstract
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.