Publication
Title
Radiosynthesis and in vivo evaluation of for P-glycoprotein imaging
Author
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 11C and evaluated in vivo for its potential to image P-gp function and expression. Radiochemical pure (>98%) [11C]MC80 was obtained within 25 min starting from [11C]methyl iodide with radiochemical yield of 26%. Biodistribution studies in FVB mice demonstrated a high baseline brain uptake (7.66 ± 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 [11C]MC80 kinetics are modulated by P-gp. Reversed phase-HPLC analysis of brain revealed an excellent metabolic profile (>90% intact [11C]MC80).
Language
English
Source (journal)
Bioorganic and medicinal chemistry. - Oxford
Publication
Oxford : 2010
ISSN
0968-0896
Volume/pages
18:17(2010), p. 6489-6495
ISI
000281203300030
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 05.03.2014
Last edited 27.09.2017