Radiosynthesis and in vivo evaluation of [¹¹C]MC80 for P-glycoprotein imaging

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• 作者：Sylvie De Bruyne ; Leonie wyffels ; Lieselotte Moerman ; Johan Sambre ; Nicola A. Colabufo ; Francesco Berardi ; Roberto Perrone ; Filip De Vos
• 关键词：P-glycoprotein ; PET ; Blood– ; brain barrier ; Drug resistance
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：1 September 2010
• 年：2010
• 卷：18
• 期：17
• 页码：6489-6495
• 全文大小：480 K

文摘

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).