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Titolo:
Absolute quantification by positron emission tomography of the endogenous ligand
Autore:
Delforge, J; Bottlaender, M; Pappata, S; Loch, C; Syrota, A;
Indirizzi:
CEA, Serv Hosp Frederic Joliot, F-91406 Orsay, France CEA Orsay France F-91406 erv Hosp Frederic Joliot, F-91406 Orsay, France
Titolo Testata:
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
fascicolo: 5, volume: 21, anno: 2001,
pagine: 613 - 630
SICI:
0271-678X(200105)21:5<613:AQBPET>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
BENZODIAZEPINE RECEPTOR CONCENTRATION; STRIATAL DOPAMINE RELEASE; C-11 RACLOPRIDE; HUMAN-BRAIN; KINETIC-PROPERTIES; H-3 RACLOPRIDE; BASAL GANGLIA; PET; BINDING; INVIVO;
Keywords:
apparent affinity; endogenous ligand; ligand-receptor model; quantification by positron emission tomography;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Delforge, J Ctr Etud Bruyeres Le Chatel, CEA, Lab Radiotoxicol, BP 12, F-91680 Bruyeres Le Chatel, France Ctr Etud Bruyeres Le Chatel BP 12 Bruyeres Le Chatel France F-91680
Citazione:
J. Delforge et al., "Absolute quantification by positron emission tomography of the endogenous ligand", J CEREBR B, 21(5), 2001, pp. 613-630

Abstract

The results of several recent papers have shown a significant influence ofthe endogenous neurotransmitters on the exogenous ligand kinetics measuredby positron emission tomography. For example, several groups found that the percentage of D2 receptor sites occupied by the endogenous dopamine ranged from 25% to 40% at basal level. An obvious consequence of this significant occupancy is that the ligand-receptor model parameters, usually estimatedby a model that does not rake into account the endogenous ligand (EL) kinetics, can be significantly biased. In the current work, the authors studiedthe biases obtained by using the multiinjection approach. The results showed that in the classical ligand-receptor model, the receptor concentration is correctly estimated and that only the apparent affinity is biased by nottaking the EL into account. At present, all absolute quantifications of the EL have been obtained through pharmacologic manipulation of the endogenous transmitter concentration, which is often too invasive a method to be used in patients. A theoretical reasoning showed that a noninvasive approach is necessarily based on both the apparent affinity measurement and on a multiregion approach. The correlation between the receptor concentration and the apparent affinity, previously observed with some ligands, verifies these two conditions: thus, the authors suggest that this correlation could be the result of the EL effect. To test this assumption experimentally, the effect of reserpine-induced dopamine depletion on the interactions between the D2 receptor sites and the FLB 457 is studied. With untreated baboons, the apparent FLB 457 affinity was smaller in the receptor-rich regions (striatum) than in the receptor-poor regions. This discrepancy disappeared after dopamine depletion, strongly suggesting that this affinity difference was related to the EL effect. Therefore, the purpose of the current study was to test the ability to quantify the EL based on the observed correlation betweenthe receptor concentration and the apparent affinity. This approach offersa method fur estimating the percentage of receptor sites occupied by the EL and, if its affinity is known, the free EL concentration. From the data obtained using FLB 457 with baboons, the authors found that approximately 53% of the D2 receptor sites are occupied by dopamine in the striatum and that the free dopamine concentration is approximately 120 nmol/L at basal level. This approach is transferable to patients, because the experimental dataare obtained without pharmacologically induced modification of the EL.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/01/20 alle ore 15:32:49