Home > Publications database > Metabolism of the A1 adenosine receptor PET ligand [18F]CPFPX by CYP1A2: implications for bolus/infusion PET studies > print

001     52934
005     20200617075724.0
024 7 _ |2 pmid
|a pmid:17045169
024 7 _ |2 DOI
|a 10.1016/j.nucmedbio.2006.07.006
024 7 _ |2 WOS
|a WOS:000241530100009
024 7 _ |2 ISSN
|a 1872-9414
037 _ _ |a PreJuSER-52934
041 _ _ |a eng
082 _ _ |a 610
084 _ _ |2 WoS
|a Radiology, Nuclear Medicine & Medical Imaging
100 1 _ |0 P:(DE-Juel1)138474
|a Matusch, A.
|b 0
|u FZJ
245 _ _ |a Metabolism of the A1 adenosine receptor PET ligand [18F]CPFPX by CYP1A2: implications for bolus/infusion PET studies
260 _ _ |a Amsterdam [u.a.]
|b Elsevier
|c 2006
300 _ _ |a 891 - 898
336 7 _ |0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
|a Journal Article
336 7 _ |2 DataCite
|a Output Types/Journal article
336 7 _ |0 0
|2 EndNote
|a Journal Article
336 7 _ |2 BibTeX
|a ARTICLE
336 7 _ |2 ORCID
|a JOURNAL_ARTICLE
336 7 _ |2 DRIVER
|a article
440 _ 0 |0 4644
|a Nuclear Medicine and Biology
|v 33
|x 0883-2897
500 _ _ |a Record converted from VDB: 12.11.2012
520 _ _ |a The 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.
536 _ _ |0 G:(DE-Juel1)FUEK409
|2 G:(DE-HGF)
|a Funktion und Dysfunktion des Nervensystems
|c P33
|x 0
588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Animals
650 _ 2 |2 MeSH
|a Cytochrome P-450 CYP1A2: metabolism
650 _ 2 |2 MeSH
|a Cytochromes
650 _ 2 |2 MeSH
|a Infusions, Parenteral
650 _ 2 |2 MeSH
|a Male
650 _ 2 |2 MeSH
|a Metabolic Clearance Rate
650 _ 2 |2 MeSH
|a Positron-Emission Tomography: methods
650 _ 2 |2 MeSH
|a Rats
650 _ 2 |2 MeSH
|a Rats, Inbred F344
650 _ 2 |2 MeSH
|a Receptor, Adenosine A1: metabolism
650 _ 2 |2 MeSH
|a Xanthines: administration & dosage
650 _ 2 |2 MeSH
|a Xanthines: diagnostic use
650 _ 2 |2 MeSH
|a Xanthines: pharmacokinetics
650 _ 7 |0 0
|2 NLM Chemicals
|a 8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine
650 _ 7 |0 0
|2 NLM Chemicals
|a Cytochromes
650 _ 7 |0 0
|2 NLM Chemicals
|a Receptor, Adenosine A1
650 _ 7 |0 0
|2 NLM Chemicals
|a Xanthines
650 _ 7 |0 9035-50-1
|2 NLM Chemicals
|a cytochrome P-448
650 _ 7 |0 EC 1.14.14.1
|2 NLM Chemicals
|a Cytochrome P-450 CYP1A2
650 _ 7 |2 WoSType
|a J
653 2 0 |2 Author
|a CPFPX
653 2 0 |2 Author
|a CYP1a2
653 2 0 |2 Author
|a radio-TLC
653 2 0 |2 Author
|a PET
653 2 0 |2 Author
|a fluvoxamine
700 1 _ |0 P:(DE-HGF)0
|a Meyer, P. T.
|b 1
700 1 _ |0 P:(DE-Juel1)VDB2513
|a Bier, D.
|b 2
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB20516
|a Holschbach, M. H.
|b 3
|u FZJ
700 1 _ |0 P:(DE-HGF)0
|a Woitalla, D.
|b 4
700 1 _ |0 P:(DE-Juel1)131679
|a Elmenhorst, D.
|b 5
|u FZJ
700 1 _ |0 P:(DE-Juel1)VDB59790
|a Winz, O. H.
|b 6
|u FZJ
700 1 _ |0 P:(DE-Juel1)131714
|a Zilles, K.
|b 7
|u FZJ
700 1 _ |0 P:(DE-Juel1)131672
|a Bauer, A.
|b 8
|u FZJ
773 _ _ |0 PERI:(DE-600)1498538-x
|a 10.1016/j.nucmedbio.2006.07.006
|g Vol. 33, p. 891 - 898
|p 891 - 898
|q 33<891 - 898
|t Nuclear medicine and biology
|v 33
|x 1872-9614
|y 2006
856 7 _ |u http://dx.doi.org/10.1016/j.nucmedbio.2006.07.006
909 C O |o oai:juser.fz-juelich.de:52934
|p VDB
913 1 _ |0 G:(DE-Juel1)FUEK409
|b Gesundheit
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|l Funktion und Dysfunktion des Nervensystems
|v Funktion und Dysfunktion des Nervensystems
|x 0
914 1 _ |y 2006
915 _ _ |0 StatID:(DE-HGF)0010
|a JCR/ISI refereed
920 1 _ |0 I:(DE-Juel1)VDB54
|d 31.12.2006
|g IME
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|l Institut für Medizin
|x 0
920 1 _ |0 I:(DE-Juel1)VDB53
|d 31.12.2006
|g INC
|k INC
|l Institut für Nuklearchemie
|x 1
920 1 _ |0 I:(DE-82)080010_20140620
|g JARA
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|l Jülich-Aachen Research Alliance - Translational Brain Medicine
|x 2
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980 _ _ |a UNRESTRICTED
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981 _ _ |a I:(DE-Juel1)INM-5-20090406
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