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000052934 0247_ $$2DOI$$a10.1016/j.nucmedbio.2006.07.006
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000052934 084__ $$2WoS$$aRadiology, Nuclear Medicine & Medical Imaging
000052934 1001_ $$0P:(DE-Juel1)138474$$aMatusch, A.$$b0$$uFZJ
000052934 245__ $$aMetabolism of the A1 adenosine receptor PET ligand [18F]CPFPX by CYP1A2: implications for bolus/infusion PET studies
000052934 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2006
000052934 300__ $$a891 - 898
000052934 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000052934 440_0 $$04644$$aNuclear Medicine and Biology$$v33$$x0883-2897
000052934 500__ $$aRecord converted from VDB: 12.11.2012
000052934 520__ $$aThe A1 adenosine receptor positron emission tomography (PET) ligand 8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine ([18F]CPFPX, ) undergoes a fast hepatic metabolism. An optimal design of PET quantitation approaches (e.g., bolus/infusion studies) necessitates the knowledge of factors that influence this metabolism. Metabolites of were separated by radio thin-layer chromatography. Metabolism in vivo, in pooled human liver microsomes and in recombinant human cytochrome isoenzyme preparations was studied. Dynamic PET studies using were performed on three controls and two patients, one treated with the antidepressant and inhibitor of cytochrome CYP1A2 fluvoxamine, the other suffering from liver cirrhosis. CPFPX is metabolized by cytochrome CYP1A2 with high selectivity [KM=1.1 microM (95% confidence interval, or CI, 0.6-2.0 microM) and Vmax=243 pmol min(-1) mg(-1) (95% CI, 112-373 pmol min(-1) mg(-1)) corresponding to 2.4 pmol min(-1) pmol(-1) cytochrome P-450]. This metabolism can competitively be inhibited by fluvoxamine with KI=68 nM (95% CI, 34-138 nM). At least eight compounds found in human plasma and in the CYP1A2 in vitro preparations have an identical migration pattern and account together for >90% and >80% of the respective metabolite yield. Metabolism was considerably delayed in the two patients. In conclusion, is metabolized by cytochrome CYP1A2. Its metabolism is therefore subdued to disease-related or xenobiotic-induced changes of CYP1A2 activity. The identification of the metabolic pathway of 1 allows to optimize image quantification in A1 adenosine receptor PET studies.
000052934 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems$$cP33$$x0
000052934 588__ $$aDataset connected to Web of Science, Pubmed
000052934 65320 $$2Author$$aCPFPX
000052934 65320 $$2Author$$aCYP1a2
000052934 65320 $$2Author$$aradio-TLC
000052934 65320 $$2Author$$aPET
000052934 65320 $$2Author$$afluvoxamine
000052934 650_2 $$2MeSH$$aAnimals
000052934 650_2 $$2MeSH$$aCytochrome P-450 CYP1A2: metabolism
000052934 650_2 $$2MeSH$$aCytochromes
000052934 650_2 $$2MeSH$$aInfusions, Parenteral
000052934 650_2 $$2MeSH$$aMale
000052934 650_2 $$2MeSH$$aMetabolic Clearance Rate
000052934 650_2 $$2MeSH$$aPositron-Emission Tomography: methods
000052934 650_2 $$2MeSH$$aRats
000052934 650_2 $$2MeSH$$aRats, Inbred F344
000052934 650_2 $$2MeSH$$aReceptor, Adenosine A1: metabolism
000052934 650_2 $$2MeSH$$aXanthines: administration & dosage
000052934 650_2 $$2MeSH$$aXanthines: diagnostic use
000052934 650_2 $$2MeSH$$aXanthines: pharmacokinetics
000052934 650_7 $$00$$2NLM Chemicals$$a8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine
000052934 650_7 $$00$$2NLM Chemicals$$aCytochromes
000052934 650_7 $$00$$2NLM Chemicals$$aReceptor, Adenosine A1
000052934 650_7 $$00$$2NLM Chemicals$$aXanthines
000052934 650_7 $$09035-50-1$$2NLM Chemicals$$acytochrome P-448
000052934 650_7 $$0EC 1.14.14.1$$2NLM Chemicals$$aCytochrome P-450 CYP1A2
000052934 650_7 $$2WoSType$$aJ
000052934 7001_ $$0P:(DE-HGF)0$$aMeyer, P. T.$$b1
000052934 7001_ $$0P:(DE-Juel1)VDB2513$$aBier, D.$$b2$$uFZJ
000052934 7001_ $$0P:(DE-Juel1)VDB20516$$aHolschbach, M. H.$$b3$$uFZJ
000052934 7001_ $$0P:(DE-HGF)0$$aWoitalla, D.$$b4
000052934 7001_ $$0P:(DE-Juel1)131679$$aElmenhorst, D.$$b5$$uFZJ
000052934 7001_ $$0P:(DE-Juel1)VDB59790$$aWinz, O. H.$$b6$$uFZJ
000052934 7001_ $$0P:(DE-Juel1)131714$$aZilles, K.$$b7$$uFZJ
000052934 7001_ $$0P:(DE-Juel1)131672$$aBauer, A.$$b8$$uFZJ
000052934 773__ $$0PERI:(DE-600)1498538-x$$a10.1016/j.nucmedbio.2006.07.006$$gVol. 33, p. 891 - 898$$p891 - 898$$q33<891 - 898$$tNuclear medicine and biology$$v33$$x1872-9614$$y2006
000052934 8567_ $$uhttp://dx.doi.org/10.1016/j.nucmedbio.2006.07.006
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000052934 9201_ $$0I:(DE-Juel1)VDB54$$d31.12.2006$$gIME$$kIME$$lInstitut für Medizin$$x0
000052934 9201_ $$0I:(DE-Juel1)VDB53$$d31.12.2006$$gINC$$kINC$$lInstitut für Nuklearchemie$$x1
000052934 9201_ $$0I:(DE-82)080010_20140620$$gJARA$$kJARA-BRAIN$$lJülich-Aachen Research Alliance - Translational Brain Medicine$$x2
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