Abstract
Sertraline hydrochloride (Zoloft®, 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 [11C]sertraline kinetic parameters and the feasibility of semi-quantitative approach for assessing distribution volume ratio (DVR). [11C]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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Boecker, H., Sprenger, T., Henriksen, G., Toelle, T. R., and Spilker, M. E., Optimal duration of PET studies with 18Ffluoroethyl-diprenorphine. J. Nucl. Med., 46, 2092–2096 (2005).
Dahl, A. A., Ravindran, A., Allgulander, C., Kutcher, S. P., Austin, C., and Burt, T., Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors. Acta Psychiat. Scand., 111, 429–435 (2005).
Dayan, P. and Huys, Q. J., Serotonin, inhibition, and negative mood. PLos. Comput. Biol., 4, e4 (2008).
Esposito, E., Serotonin-dopamine interaction as a focus of novel antidepressant drugs. Curr. Drug Targets, 7, 177–185 (2006).
Fazaeli, Y., Jalilian, A. R., Amini, M. M., Ardaneh, K., Rahiminejad, A., Bolourinovin, F., Moradkhani, S., and Majdabadi, A., Development of a 68Ga-fluorinated porphyrin complex as a possible PET imaging agent. Nucl. Med. Mol. Imaging, 46, 20–26 (2011)
Frankle, W. G., Huang, Y., Hwang, D. R., Talbot, P. S., Slifstein, M., Van Heertum, R., Abi-Dargham, A., and Laruelle, M., Comparative evaluation of serotonin transporter radioligands 11C-DASB and 11C-McN 5652 in healthy humans. J. Nucl. Med., 45, 682–694 (2004).
Huang, T. Y., Hwang, D. R., Narendran, R., Sudo, Y., Chatterjee, R., Bae, S. A., Mawiawi, O., Kegeles, L. S., Wilson, A. A., Kung, H. F., and Laruelle, M., Comparative evaluation in nonhuman primates of five PET radiotracers for imaging the serotonin transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM. J. Cereb. Blood Flow Metab., 22, 1377–1398 (2002).
Kapur, S. and Remington, G., Serotonin-dopamine interaction and its relevance to schizophrenia. Am. J. Psychiatry, 153, 466–476 (1996).
Kim, S. J., Lee, J. S., Im, K. C., Kim, S. Y., Park, S. A., Lee, S. J., Oh, S. J., Lee, D. S., and Moon, D. H., Kinetic modeling of 3′-deoxy-3′-18F-fluorothymidine for quantitative cell proliferation imaging in subcutaneous tumor models in mice. J. Nucl. Med., 49, 2057–2066 (2008a).
Kim, S. J., Lee, J. S., Kim, Y. K., Frost, J., Wand, G., McCaul, M. E., and Lee, D. S., Multiple linear analysis methods for the quantification of irreversibly binding radiotracers. J. Cereb. Blood Flow Metab., 28, 1965–1977(2008b)
Kim, S. W., Park, S. Y., and Hwang, O., Up-regulation of tryptophan hydroxylase expression and serotonin synthesis by sertraline. Mol. Pharmacol., 61, 778–785 (2002).
Lee, J. S., Lee, D. S., Kim, S. J., Kim, Y. K., Kang, E., Kang, H., Kang, K. W., Lee, J. M., Kim, J. J., Park, H. J., Kwon, J. S., Kim, S. I., Yoo, T. W., Chang, K. H., and Lee, M. C., Development of korean standard brain templates. J. Korean Med. Sci., 20, 483–488 (2005).
Lee, J. S., Lee, D. S., Ahn, J. Y., Yeo, J. S., Cheon, G. J., Kim, S. K., Park, K. S., Chung, J. K., and Lee, M. C., Generation of parametric image of regional myocardial blood flow using H(2)(15)O dynamic PET and a linear least-squares method. J. Nucl. Med., 46, 1687–1695 (2005).
Lim, K. S., Kwon, J. S., Jang, I. J., Jeong, J. M., Lee, J. S., Kim, H. W., Kang, W. J., Kim, J. R., Cho, J. Y., Kim, E., Yoo, S. Y., Shin, S. G., and Yu, K. S., Modeling of brain D2 receptor occupancy-plasma concentration relationships with a novel antipsychotic, YKP1358, using serial PET scans in healthy volunteers. Clin. Pharmacol. Ther., 81, 252–258 (2007).
Lopresti, B. J., Klunk, W. E., Mathis, C. A., Hoge, J. A., Ziolko, S. K., Lu, X., Meltzer, C. C., Schimmel, K., Tsopelas, N. D., DeKosky, S. T., and Price, J. C., Simplified quantification of pittsburghcompound β amyloid imaging PET studies:a comparative analysis. J. Nucl. Med., 46, 1959–1972 (2005).
Ludden, T. M., Beal, S. L., and Sheiner, L. B., Comparison of the akaike information criterion, the schwarz criterion and the F-test as guides to model selection. J. Pharmacokinet. Biopharm., 22, 431–445 (1994).
Munhoz, R. P., Serotonin syndrome induced by a combination of bupropion and SSRIs. Clin. Neuropharmacol., 27, 219–222 (2004).
Sanacora, G., Mason, G. F., Rothman, D. L., and Krystal, J. H., Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. Am. J. Psychiatry, 159, 663–665 (2002).
Shields, A. F. and Price, P., In vivo imaging of cancer therapy: An Overview, In Saleem, A. and Price, P. (Eds.). Positron emission tomography measurement of drugkinetics. Springer, pp. 169–204, (2007).
Szabo, Z., Scheffel, U., Mathews, W. B., Ravert, H. T., Szabo, K., Kraut, M., Palmon, S., Ricaurte, G. A., and Dannals, R. F., Kinetic analysis of [11C]McN5652: A serotonin transporter radioligand. J. Cereb. Blood Flow Metab., 19, 967–981 (1999).
Valk, P. E., Bailey, D. L., Townsend, D. W., and Maisey, M. N., Positron emission tomography: An Overview, In Carson, R. E. (Eds.). Tracer kinetic modeling in PET. Springer, pp. 147–179, (2003).
Voineskos, A. N., Wilson, A. A., Boovariwala, A., Saqrati, S., Houle, S., Rusjan, P., Sokolove, S., Spencer, E. P., Ginovart, N., and Meyer, J. H., Serotonin transporteroccupancy of high-dose selective serotonin reuptake inhibitors during majordepressive disorder measured with [11C] DASB positron emission tomography. Psychopharmacology, 193, 539–545 (2007).
Yamaoka, K., Nakagawa, T., and Uno, T., Application of Akaike’s information criterion (AIC) in the evaluationof linear pharmacokinetic equations. J. Pharmacokinet. Biopharm., 6, 165–175 (1978).
Zhu, A. and Shim, H., Current Molecular Imaging Positron Emitting Radiotracers in Oncology. Nucl. Med. Mol. Imaging, 45, 1–14 (2011).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, J.W., Lee, J.S., Kim, S.J. et al. Compartmental modeling and simplified quantification of [11C]sertraline distribution in human brain. Arch. Pharm. Res. 35, 1591–1597 (2012). https://doi.org/10.1007/s12272-012-0910-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-012-0910-4