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Titolo:
Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [F-18]altanserin in human and rodent
Autore:
Tan, PZ; Baldwin, RM; Van Dyck, CH; Al-Tikriti, M; Roth, B; Khan, N; Charney, DS; Innis, RB;
Indirizzi:
Yale Univ, Sch Med, Dept Psychiat 116A2, VA Med Ctr,Yale VA Pet Ctr, W Haven, CT 06511 USA Yale Univ W Haven CT USA 06511 Ctr,Yale VA Pet Ctr, W Haven, CT 06511 USA Case Western Reserve Univ, Sch Med, Cleveland, OH USA Case Western ReserveUniv Cleveland OH USA v, Sch Med, Cleveland, OH USA
Titolo Testata:
NUCLEAR MEDICINE AND BIOLOGY
fascicolo: 6, volume: 26, anno: 1999,
pagine: 601 - 608
SICI:
0969-8051(199908)26:6<601:CORMO5>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; F-18 ALTANSERIN; HUMAN BRAIN; BINDING; RADIOLIGAND; KETANSERIN; RATS;
Keywords:
altanserin; serotonin-2A; PET; fluorine-18; metabolism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Tan, PZ Yale Univ, Sch Med, Dept Psychiat 116A2, VA Med Ctr,Yale VA Pet Ctr, 333 Cedar St, W Haven, CT 06511 USA Yale Univ 333 Cedar St W Haven CT USA 06511 W Haven, CT 06511 USA
Citazione:
P.Z. Tan et al., "Characterization of radioactive metabolites of 5-HT2A receptor PET ligand [F-18]altanserin in human and rodent", NUCL MED BI, 26(6), 1999, pp. 601-608

Abstract

This study was performed to identify and characterize the radiometabolitesof the serotonin 5-HT2A receptor ligand [F-18]altanserin in supporting quantification of the target receptors by positron emission tomography. In analogy to its analog ketanserin, we postulated 4-(4 fluorobenzoyl)piperidine (FBP) and altanserinol for the previously observed two polar radiometabolites, corresponding to dealkylation at the piperidine nitrogen and reduction at the ketone, respectively. To test this hypothesis and characterize the in vivo and in vitro behavior of the radiometabolites, we synthesized nonradioactive authentic compounds altanserinol, 1-(4-fluorophenyl)-1-(piperidin-4-yl)meth (FBPOH), and isolated nonradioactive FBP metabolite from monkey plasma. [F-18]Altanserinol was obtained by NaBH4 reduction of [F-18]altanserin, followed by acid hydrolysis. Identification of radiometabolites was carried out by high performance liquid chromatography and thin layer chromatography comparison of the radioactive plasma after injection of tracers with five authentic compounds. Human studies revealed that at least four radiometabolites, one identified as [F-18]altanserinol, resulted from reduction ofthe ketone functionality. The N-dealkylation product [F-18]FBP was not detectable; however, a radiometabolite of FBP was present in plasma after administration of [F-18]altanserin. Monkey studies showed nonradioactive FBP was converted rapidly to a less polar metabolite. In rat, altanserin and altanserinol were converted to each other in vivo, and all the radiometaboliteslikely penetrated the blood-brain barrier and entered the brain. Displacement binding of altanserin to cloned serotonin 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors showed K-i values of 0.3, 6.0, 1,756, and 15 nM; the binding of FBP and altanserinol to these four 5-HT subtypes was negligible. We conclude from these studies that the radiometabolites of [F-18]altanserin from N-dealkylation and ketone reduction should not interfere with specific receptor quantification in an equilibrium paradigm. NUCL MED BIOL 26;6:601-608,1999. (C) 1999 Elsevier Science Inc. All rights reserved.

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Documento generato il 18/01/20 alle ore 02:05:35