4.6 Article

Compartmental modeling and simplified quantification of [11C]sertraline distribution in human brain

期刊

ARCHIVES OF PHARMACAL RESEARCH
卷 35, 期 9, 页码 1591-1597

出版社

PHARMACEUTICAL SOC KOREA
DOI: 10.1007/s12272-012-0910-4

关键词

Kinetic modeling; Serotonin transporters; Pharmacokinetics; PET; [C-11]sertraline; Microdose

资金

  1. Ministry of Health, Welfare & Family Affairs, Republic of Korea [A070001]
  2. National Research Foundation of Korea (NRF)
  3. Korea government (MEST) [2011-0018636]

向作者/读者索取更多资源

Sertraline hydrochloride (ZoloftA (R), Pfizer) is an antidepressant drug of the selective serotonin reuptake inhibitor (SSRI). The aims of this study were evaluating its in vivo distribution and kinetic models in human brain. Also, this study was to determine optimal scan duration of dynamic positron emission tomography (PET) for accurate [C-11]sertraline kinetic parameters and the feasibility of semi-quantitative approach for assessing distribution volume ratio (DVR). [C-11]sertraline dynamic PET and magnetic resonance imaging (MRI) scans were performed in 5 healthy males. Blood sampling were collected for the input function. Tissue time-activity curves (TAC) were obtained in 7 brain regions using MRI. Goodness-of-fit for TAC using simple tissue compartment model (2C2P) and 3-compartment models with irreversible (3C3P) and reversible (3C4P) were compared. Total distribution volume (DV) for each region of interest (ROI) and DVR were calculated. Also, ratio between the standard uptake value (SUV) of each ROI and that of cerebellum (SUVr) was computed and correlated with the DVR. Akaike information criteria analysis showed that the 2C2P was the most suitable model. Average values of K (1) (mL/min/g) and k (2) (1/min) were 0.54 and 0.012 in putamen. PET scan time longer than 50 min was required for the accurate estimation of DV. SUVr in 50-90 min was well correlated with DVR.

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