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Titolo:
Carbon-11 PB-12: An attempt to visualize the dopamine D-4 receptor in the primate brain with positron emission tomography
Autore:
Langer, O; Halldin, C; Chou, YH; Sandell, J; Swahn, CG; Nagren, K; Perrone, R; Berardi, F; Leopoldo, M; Farde, L;
Indirizzi:
Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-17176 Sect, S-17176 Stockholm, Sweden Turku Pet Ctr, Radiopharmaceut Chem Lab, Turku, Finland Turku Pet Ctr Turku Finland r, Radiopharmaceut Chem Lab, Turku, Finland Univ Bari, Dipartimento Farmacochim, Bari, Italy Univ Bari Bari ItalyUniv Bari, Dipartimento Farmacochim, Bari, Italy
Titolo Testata:
NUCLEAR MEDICINE AND BIOLOGY
fascicolo: 8, volume: 27, anno: 2000,
pagine: 707 - 714
SICI:
0969-8051(200011)27:8<707:CPAATV>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
C-11 METHYL TRIFLATE; I-125 EPIDEPRIDE; HIGH-AFFINITY; D4 RECEPTORS; RAT-BRAIN; PET; BINDING; LIGAND; LOCALIZATION; RADIOLIGANDS;
Keywords:
dopamine D-4 receptor; [C-11]PB-12; PET; brain; primate;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Langer, O Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden Karolinska Hosp Stockholm Sweden S-17176 176 Stockholm, Sweden
Citazione:
O. Langer et al., "Carbon-11 PB-12: An attempt to visualize the dopamine D-4 receptor in the primate brain with positron emission tomography", NUCL MED BI, 27(8), 2000, pp. 707-714

Abstract

The dopamine D-4 receptor (D4R) is expressed in low density in various extrastriatal brain regions. This receptor subtype is discussed in relation tothe pathophysiology and treatment of schizophrenia but no selective positron emission tomography (PET) ligand is available to date to study the distribution in vivo. The arylpiperazine derivative N-[2-[4-(4-chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (PB-12) is a never, high affinity (K-i= 0.040 nM) and selective D4R ligand. We radiolabeled PB-12 with carbon-11(t(1/2) 20.4 min) by O-methylation of the corresponding desmethyl analogueN-[2-[4-(4-chloro phenyl)piperazin-1-yl]ethyl]-3-hydroxybenzamide (LM-190)with [C-11]methyl triflate. Derivative LM-190 was prepared by condensing 3-hydroxybenzoic acid with the appropriate amine. For the radiolabeling, theincorporation yield was >90% and the total synthesis time including high performance liquid chromatography (HPLC) purification was about 35 min, The specific radioactivity of [C-11]PB-12 at time of injection was 67-118 GBq .mu mol(-1). PET studies in a cynomolgus monkey showed a high uptake and widespread distribution of radioactivity in the brain, including the neocortex and thalamus. About 40% of total radioactivity in plasma represented unchanged radioligand at 60 min after injection as determined by HPLC. Pretreatment with the D4R ligand 3-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}-1H-pyrollo[2,3-b]pyridine (L-745,870) prior to radioligand injection failed to demonstrate receptor specific binding in the monkey brain. Furthermore, the brain radioactivity distribution was left unaffected by pretreating with unlabeled PB-12. This failure to detect a D4R-specific signal may be related to a very low density of the D4R in primate brain, insufficient binding affinity of the radioligand, and a high background of nonspecific binding. It can be concluded from these findings that [C-11]PB-12 is not suitable to Visualize the D4R in the primate brain with PET. NUCL MED BIOL 27;8:707-714, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.

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Documento generato il 20/11/19 alle ore 02:29:53