Title
Radiosynthesis and in vivo evaluation of <tex>$[^{11}C]MC80$</tex> for P-glycoprotein imaging Radiosynthesis and in vivo evaluation of <tex>$[^{11}C]MC80$</tex> for P-glycoprotein imaging
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Oxford ,
Subject
Pharmacology. Therapy
Source (journal)
Bioorganic and medicinal chemistry. - Oxford
Volume/pages
18(2010) :17 , p. 6489-6495
ISSN
0968-0896
ISI
000281203300030
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
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).
E-info
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