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ID: ALA1240494
Journal: Bioorg Med Chem
Title: Radiosynthesis and in vivo evaluation of [(11)C]MC80 for P-glycoprotein imaging.
Authors: Bruyne SD, Wyffels L, Moerman L, Sambre J, Colabufo NA, Berardi F, Perrone R, Vos FD.
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).
CiteXplore: 20685124