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Title
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Radiosynthesis and in vivo evaluation of for P-glycoprotein imaging
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Author
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Abstract
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| 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). |
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Language
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English
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Source (journal)
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Bioorganic and medicinal chemistry. - Oxford
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Publication
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Oxford
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2010
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ISSN
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0968-0896
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DOI
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10.1016/J.BMC.2010.06.097
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Volume/pages
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18
:17
(2010)
, p. 6489-6495
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ISI
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000281203300030
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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