Optimizing an online SPE-HPLC method for analysis of (R)-[11C]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide [(R)-[11C]PK11195] and its metabolites in humans |
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| Authors: | Greuter Henri N J M van Ophemert Patricia L B Luurtsema Gert van Berckel Bart N M Franssen Eric J F Windhorst Bert D Lammertsma Adriaan A |
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| Affiliation: | Department of Nuclear Medicine and PET Research, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. hnjm.greuter@vumc.nl |
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| Abstract: | (R)-[11C]PK11195 is used as a positron emission tomography tracer for activated microglia in several neurological disorders. Quantification of specific binding requires a metabolite-corrected plasma input function. In this study, a high-performance liquid chromatography (HPLC) procedure with online solid phase extraction was modified for analyzing (R)-[11C]PK11195 plasma samples, yielding total sample recoveries of more than 98%. When applied to human studies, the use of two HPLC systems enabled analysis of up to seven plasma samples under regular conditions. Online radioactivity detection was compared with offline sample measurements of HPLC profiles. Offline measurements provided the most reliable results especially for late plasma samples. In 10 patients, an average decrease of parent compound from 94.6% at 2.5 min to 45.2% at 1 h after administration was observed. |
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