HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hwang, D.-R. Articles by Laruelle, M. Search for Related Content PubMed PubMed Citation Articles by Hwang, D.-R. Articles by Laruelle, M.

Quantitative Analysis of (-)-N-¹¹C-Propyl-Norapomorphine In Vivo Binding in Nonhuman Primates

¹ Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York
² Department of Radiology, Columbia University College of Physicians and Surgeons, New York, New York
³ New York State Psychiatric Institute, New York, New York

(-)-N-¹¹C-propyl-norapomorphine (¹¹C-NPA) is a new dopamine agonist PET radiotracer that holds potential for imaging the high-affinity states of dopamine D₂-like receptors in the living brain. The goal of this study was to develop and evaluate analytic strategies to derive in vivo ¹¹C-NPA binding parameters. Methods: Two baboons were scanned 4 times after ¹¹C-NPA injections. The metabolite-corrected arterial input functions were measured. Regional brain time-activity curves were analyzed with kinetic and graphical analyses, using the arterial time-activity curve as the input function. Data were also analyzed with the simplified reference-tissue model (SRTM) and graphical analysis with reference-region input. Results: ¹¹C-NPA exhibited moderately fast metabolism, with 31% ± 5% of arterial plasma concentration corresponding to the parent compound at 40 min after injection. Plasma clearance was 29 ± 1 L/h, and plasma free fraction (f₁) was 5% ± 1%. For kinetic analysis, a 1-tissue compartment model (1TCM) provided a good fit to the data and more robust derivations of the tissue distribution volumes (V_T, in mL/g) than a 2-tissue compartment model (2TCM). Using 1TCM, V_Ts in the cerebellum and striatum were 3.4 ± 0.4 and 7.5 ± 2 mL/g, respectively, which led to estimates of striatal binding potential (BP) of 4.0 ± 1.1 mL/g and striatal equilibrium specific-to-nonspecific partition coefficient (V₃'') of 1.2 ± 0.2. V_T values derived with graphical analysis were well correlated with but slightly lower than V_T values derived with kinetic analysis. V₃'' values derived with SRTM were well correlated with but slightly higher than V₃'' values derived with kinetic analysis. Using any method, a significant difference was detected in BP and V₃'' values between the 2 animals. It was determined that 30 min of scanning data were sufficient to derive V₃'' values using kinetic, graphical (arterial input and reference-region input), and SRTM analyses. Conclusion: This study indicates that ¹¹C-NPA is a suitable PET tracer to quantify the agonist high-affinity sites of D₂-like receptors.

Key Words: dopamine • D₂ agonist • nonhuman primate • ¹¹C-NPA • PET

This article has been cited by other articles:

				C. M. Laymon, N. S. Mason, W. G. Frankle, J. P. Carney, B. J. Lopresti, M. Y. Litschge, C. A. Mathis, J. M. Mountz, and R. Narendran Human Biodistribution and Dosimetry of the D2/3 Agonist 11C-N-Propylnorapomorphine (11C-NPA) Determined from PET J. Nucl. Med., May 1, 2009; 50(5): 814 - 817. [Abstract] [Full Text] [PDF]

				R. Narendran, D.-R. Hwang, M. Slifstein, Y. Hwang, Y. Huang, J. Ekelund, O. Guillin, E. Scher, D. Martinez, and M. Laruelle Measurement of the Proportion of D2 Receptors Configured in State of High Affinity for Agonists in Vivo: A Positron Emission Tomography Study Using [11C]N-Propyl-norapomorphine and [11C]Raclopride in Baboons J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 80 - 90. [Abstract] [Full Text] [PDF]