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Titolo:
In vivo quantification of brain serotonin transporters in humans using [C-11]McN 5652
Autore:
Parsey, RV; Kegeles, LS; Hwang, DR; Simpson, N; Abi-Dargham, A; Mawlawi, O; Slifstein, M; Van Heertum, RL; Mann, JJ; Laruelle, M;
Indirizzi:
New York State Psychiat Inst, Dept Neurosci, Div Brain Imaging, New York, NY 10032 USA New York State Psychiat Inst New York NY USA 10032 New York, NY 10032 USA Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA
Titolo Testata:
JOURNAL OF NUCLEAR MEDICINE
fascicolo: 9, volume: 41, anno: 2000,
pagine: 1465 - 1477
SICI:
0161-5505(200009)41:9<1465:IVQOBS>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; H-3 PAROXETINE BINDING; UPTAKE SITES; COMPUTED-TOMOGRAPHY; PREFRONTAL CORTEX; C-11 (+)MCN5652; BETA-CIT; PET; RADIOTRACER; DOPAMINE;
Keywords:
serotonin transporter; PET; [C-11]McN 5652; human brain; selective serotonin reuptake inhibitors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Parsey, RV New York State Psychiat Inst, Dept Neurosci, Div Brain Imaging,1051 Riverside Dr,Box 42, New York, NY 10032 USA New York State Psychiat Inst 1051 Riverside Dr,Box 42 New York NY USA 10032
Citazione:
R.V. Parsey et al., "In vivo quantification of brain serotonin transporters in humans using [C-11]McN 5652", J NUCL MED, 41(9), 2000, pp. 1465-1477

Abstract

Abnormal brain regional densities of serotonin (5-hydroxytryptamine [5-HT]) transporters have been reported in postmortem studies in several neuropsychiatric conditions, such as major depression and schizophrenia. trans-1,2,3,5,6,10-beta-Hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline ([C-11]McN 5652) is the first PET radioligand successfully developed to label 5-HT transporters in the living human brain. The purpose of this studywas to develop an imaging protocol and analytic method to measure regional5-HT transporter binding potential (BP) with [C-11]McN 5652 in humans. Methods: The arterial input function and brain uptake of (+)-[C-11]McN 5652 and (-)-[C-11]McN 5652, the active and inactive enantiomers, respectively, were measured in 6 healthy volunteers. Results: (+)-[C-11]McN 5652 concentrated in brain regions rich in 5-HT transporters (midbrain, thalamus, basal ganglia, and medial temporal lobe structures), whereas the uptake of (-)-[C-11]McN 5652 was more uniformly distributed. Total distribution volumes (VT) were derived using kinetic 2-compartment analysis and graphic analysis. VT derived by both methods were highly correlated. (+)-[C-11]McN 5652 regionalV-T ranged from 18 +/- 2 mL/g in the cerebellum to 46 +/- 13 mL/g in the midbrain. (-)-[C-11]McN 5652 regional V-T ranged from 10 +/- 2 mL/g in the cerebellum to 14 +/- 3 mL/g in the thalamus. (+)-[C-11]McN 5652 V-T were higher than (-)-[C-11]McN 5652 V-T, in all regions, including the cerebellum, a region devoid of 5-HT transporters. Blocking experiments were also performed in baboons with saturating doses of citalopram and in humans with nonsaturating doses of paroxetine. Cerebellar and neocortical (+)-[C-11]McN 5652V-T were unaffected by pretreatment with 5-HT transporter blockers. In areas of high receptor concentration (midbrain, caudate, and thalamus) 5-HT transporter blockers decreased (+)-[C-11]McN 5652 V-T to the level of cerebellum (+)-[C-11]McN 5652 VT. Conclusion: These experiments indicate that the use of the difference between (+)- and (-)-[C-11]McN 5652 V-T to define specific binding to 5-HT transporters leads to an overestimation of specific binding. 5-HT transporter BP was derived as the difference between the regional and cerebellar (+)-[C-11]McN 5652 V-T BP values were in good agreement with the distribution of 5-HT transporters in the human brain, except for regions of relatively low 5-HT transporter concentration, such as the prefrontal cortex, where no specific binding was detected using (+)-[C-11]McN 5652. (+)-[C-11]McN 5652 is an appropriate radiotracer to quantify 5-HT transporters in regions with relatively high concentration of 5-HT transporters, such as the midbrain, thalamus, and basal ganglia, and should prove useful in elucidating abnormalities of 5-HT transmission in neuropsychiatric conditions.

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Documento generato il 27/01/20 alle ore 14:38:46