phaidra.vetmeduni.ac.at o:4452 DOI 10.1177/0271678X231202336 [11C]metoclopramide is a sensitive radiotracer to measure moderate decreases in P-glycoprotein function at the blood-brain barrier The efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier limits the cerebral uptake of various xenobiotics. To assess the sensitivity of [11C]metoclopramide to measure decreased cerebral P-gp function, we performed [11C]metoclopramide PET scans without (baseline) and with partial P-gp inhibition by tariquidar in wild-type, heterozygous Abcb1a/b(+/−) and homozygous Abcb1a/b(−/−) mice as models with controlled levels of cerebral P-gp expression. Brains were collected to quantify P-gp expression with immunohistochemistry. Brain uptake of [11C]metoclopramide was expressed as the area under the brain time-activity curve (AUCbrain) and compared with data previously obtained with (R)-[11C]verapamil and [11C]N-desmethyl-loperamide. Abcb1a/b(+/−) mice had intermediate P-gp expression compared to wild-type and Abcb1a/b(−/−) mice. In baseline scans, all three radiotracers were able to discriminate Abcb1a/b(−/−) from wild-type mice (2.5- to 4.6-fold increased AUCbrain, p ≤ 0.0001). However, only [11C]metoclopramide could discriminate Abcb1a/b(+/−) from wild-type mice (1.46-fold increased AUCbrain, p ≤ 0.001). After partial P-gp inhibition, differences in [11C]metoclopramide AUCbrain between Abcb1a/b(+/−) and wild-type mice (1.39-fold, p ≤ 0.001) remained comparable to baseline. There was a negative correlation between baseline [11C]metoclopramide AUCbrain and ex-vivo-measured P-gp immunofluorescence (r = −0.9875, p ≤ 0.0001). Our data suggest that [11C]metoclopramide is a sensitive radiotracer to measure moderate, but (patho-)physiologically relevant decreases in cerebral P-gp function without the need to co-administer a P-gp inhibitor. eng P-Glycoprotein Blood-Brain Barrier PET [11C]metoclopramide Heterozygous Abcb1a/b Knockout Mice 2025-10-10T09:07:59.701Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Mairinger;Severin; FN:Severin Mairinger END:VCARD BEGIN:VCARD VERSION:3.0 N:Leterrier;S.; FN:S. Leterrier END:VCARD BEGIN:VCARD VERSION:3.0 N:Filip;Thomas; FN:Thomas Filip X-ORCID:https://orcid.org/0009-0006-9169-6032 END:VCARD BEGIN:VCARD VERSION:3.0 N:Loebsch;Mathilde; FN:Mathilde Loebsch END:VCARD BEGIN:VCARD VERSION:3.0 N:Pahnke;Jens; FN:Jens Pahnke END:VCARD BEGIN:VCARD VERSION:3.0 N:Hernández-Lozano;Irene; FN:Irene Hernández-Lozano END:VCARD BEGIN:VCARD VERSION:3.0 N:Stanek;J.; FN:J. Stanek END:VCARD BEGIN:VCARD VERSION:3.0 N:Tournier;Nicolas; FN:Nicolas Tournier END:VCARD BEGIN:VCARD VERSION:3.0 N:Zeitlinger;Markus; FN:Markus Zeitlinger END:VCARD BEGIN:VCARD VERSION:3.0 N:Hacker;Marcus; FN:Marcus Hacker END:VCARD BEGIN:VCARD VERSION:3.0 N:Langer;Oliver; FN:Oliver Langer END:VCARD BEGIN:VCARD VERSION:3.0 N:Wanek;Thomas; FN:Thomas Wanek END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 747273 https://phaidra.vetmeduni.ac.at/o:4452 https://phaidra.vetmeduni.ac.at/api/object/o:4452/thumbnail LOMv1.0 discipline