title: Radiosynthesis and in vivo evaluation of [(11)C]MC80 for P-glycoprotein imaging.
abstract: P-glycoprotein (P-gp) is an ATP-dependent efflux pump protecting the body against xenobiotics. The in vitro characterized modulator 6,7-dimethoxy-2-(6-methoxy-naphthalen-2-ylmethyl)-1,2,3,4-tetrahydroisoquinoline (MC80) of the P-gp pump was labelled with (11)C and evaluated in vivo for its potential to image P-gp function and expression. Radiochemical pure (>98%) [(11)C]MC80 was obtained within 25 min starting from [(11)C]methyl iodide with radiochemical yield of 26%. Biodistribution studies in FVB mice demonstrated a high baseline brain uptake (7.66 + or - 1.38%ID/g at 1 min pi). Cerebral uptake was increased in mdr1a knock-out mice as well as after CsA pretreatment. Pre-administration of an excess of non-radioactive MC80 caused a reduced uptake in several target organs including brain, pancreas and intestines. The results indicate that [(11)C]MC80 kinetics are modulated by P-gp. Reversed phase-HPLC analysis of brain revealed an excellent metabolic profile (>90% intact [(11)C]MC80).
authors.affiliation: Laboratory for Radiopharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium. sylviedebruyne@hotmail.com
authors.forename: Sylvie De
authors.initials: SD
authors.lastname: Bruyne
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
authors.forename: Lieselotte
authors.initials: L
authors.lastname: Moerman
authors.forename: Johan
authors.initials: J
authors.lastname: Sambre
authors.forename: Nicola A
authors.initials: NA
authors.lastname: Colabufo
authors.forename: Francesco
authors.initials: F
authors.lastname: Berardi
authors.forename: Roberto
authors.initials: R
authors.lastname: Perrone
authors.forename: Filip De
authors.initials: FD
authors.lastname: Vos
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: C555688:6,7-dimethoxy-2-(6-methoxynaphthalen-2-ylmethyl)-1,2,3,4-tetrahydroisoquinoline; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D044005:Tetrahydroisoquinolines