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@ARTICLE{Matusch:52934,
author = {Matusch, A. and Meyer, P. T. and Bier, D. and Holschbach,
M. H. and Woitalla, D. and Elmenhorst, D. and Winz, O. H.
and Zilles, K. and Bauer, A.},
title = {{M}etabolism of the {A}1 adenosine receptor {PET} ligand
[18{F}]{CPFPX} by {CYP}1{A}2: implications for
bolus/infusion {PET} studies},
journal = {Nuclear medicine and biology},
volume = {33},
issn = {1872-9614},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {PreJuSER-52934},
pages = {891 - 898},
year = {2006},
note = {Record converted from VDB: 12.11.2012},
abstract = {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.},
keywords = {Animals / Cytochrome P-450 CYP1A2: metabolism / Cytochromes
/ Infusions, Parenteral / Male / Metabolic Clearance Rate /
Positron-Emission Tomography: methods / Rats / Rats, Inbred
F344 / Receptor, Adenosine A1: metabolism / Xanthines:
administration $\&$ dosage / Xanthines: diagnostic use /
Xanthines: pharmacokinetics /
8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine (NLM
Chemicals) / Cytochromes (NLM Chemicals) / Receptor,
Adenosine A1 (NLM Chemicals) / Xanthines (NLM Chemicals) /
cytochrome P-448 (NLM Chemicals) / Cytochrome P-450 CYP1A2
(NLM Chemicals) / J (WoSType)},
cin = {IME / INC / JARA-BRAIN},
ddc = {610},
cid = {I:(DE-Juel1)VDB54 / I:(DE-Juel1)VDB53 /
$I:(DE-82)080010_20140620$},
pnm = {Funktion und Dysfunktion des Nervensystems},
pid = {G:(DE-Juel1)FUEK409},
shelfmark = {Radiology, Nuclear Medicine $\&$ Medical Imaging},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:17045169},
UT = {WOS:000241530100009},
doi = {10.1016/j.nucmedbio.2006.07.006},
url = {https://juser.fz-juelich.de/record/52934},
}