HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS 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 Related articles in JNM 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 Staley, J. K. Articles by Seibyl, J. P. Search for Related Content PubMed PubMed Citation Articles by Staley, J. K. Articles by Seibyl, J. P.

¹²³I-5-IA-85380 SPECT Measurement of Nicotinic Acetylcholine Receptors in Human Brain by the Constant Infusion Paradigm: Feasibility and Reproducibility

¹ Department of Psychiatry, Yale University School of Medicine and the Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut
² Institute for Neurodegenerative Disorders, New Haven, Connecticut

¹²³I-5-IA-85380 (¹²³I-5-IA; [¹²³I]-5-iodo-3-[2(S)-azetidinylmethoxy]pyridine) is a promising SPECT radiotracer for imaging ß₂-containing nicotinic acetylcholine receptors (ß₂-nAChRs) in brain. ß₂-nAChRs are the initial site of action of nicotine and are implicated in various neuropsychiatric disorders. The feasibility and reproducibility of the bolus-plus-constant-infusion paradigm for equilibrium modeling of ¹²³I-5-IA using SPECT in healthy nonsmokers was studied. Methods: Ten healthy nonsmokers (mean age ± SD, 43.7 ± 9.9 y) underwent two ¹²³I-5-IA SPECT scans within 4 wk. ¹²³I-5-IA was administered as a bolus (125.8 ± 14.6 MBq) plus constant infusion (18.1 ± 1.5 MBq/h). SPECT acquisitions (30 min) and venous blood sampling were performed every 60 min throughout the infusion (10–14 h). The test–retest variability and reliability of plasma activity (kBq/mL), the regional brain activity reflected by units of kBq/mL and %ID/mL (injected dose/mL brain tissue), and the equilibrium outcome measures V_T' (ratio of total uptake to total plasma parent concentration) and V_T (ratio of total uptake to free plasma parent concentration) were evaluated in 4 brain areas, including thalamus, striatum, cortex, and cerebellum. Results: Linear regression analysis revealed that time–activity curves for both plasma and brain ¹²³I-5-IA activity stabilized by 5 h, with an average change of [2.5%/h between 6 and 8 h of infusion, permitting equilibrium modeling. The plasma free fraction (f₁), total parent, and clearance demonstrated good test–retest variability (mean, 10.9%–12.5%), whereas the variability of free parent was greater (mean, 24.3%). Regional brain activity (kBq/mL) demonstrated good test–retest variability (11.1%–16.4%) that improved when corrected for infusion rate (mean, 8.2%–9.9%) or for injected dose (mean, 9.5%–13.3%). V_T' demonstrated better test–retest variability (mean, 7.0%–8.9%) than V_T (mean, 12.9%–14.6%). Reliability assessed by the intraclass correlation coefficient (ICC) was superior for kBq/mL (ICC = 0.83–0.90) and %ID/mL (ICC = 0.93–0.96) compared with V_T' (ICC = 0.30–0.64) and V_T (ICC = 0.28–0.60). The lower reliability of V_T was attributed to the poor reliability of the free fraction (ICC = 0.35) and free parent (ICC = 0.68). Conclusion: These results support the feasibility and reproducibility of equilibrium imaging with ¹²³I-5-IA for measurement of ß₂-nAChRs in human brain.

Key Words: ¹²³I-5-IA-85380 • SPECT • nicotinic acetylcholine receptor

Related articles in JNM:

THIS MONTH IN JNM

JNM 2005 46: 8a-9a. [Full Text]  

This article has been cited by other articles:

				T. B. Baker, K. M. Cummings, D. K. Hatsukami, C. A. Johnson, C. Lerman, R. Niaura, and S. S. O'Malley Transdisciplinary Tobacco Use Research Centers: Research achievements and future implications Nicotine Tob Res, October 1, 2009; 11(10): 1231 - 1244. [Full Text] [PDF]

				E. M. Mitsis, K. M. Reech, F. Bois, G. D. Tamagnan, M. G. MacAvoy, J. P. Seibyl, J. K. Staley, and C. H. van Dyck 123I-5-IA-85380 SPECT Imaging of Nicotinic Receptors in Alzheimer Disease and Mild Cognitive Impairment J. Nucl. Med., September 1, 2009; 50(9): 1455 - 1463. [Abstract] [Full Text] [PDF]

				K. P. Cosgrove, J. Batis, F. Bois, P. K. Maciejewski, I. Esterlis, T. Kloczynski, S. Stiklus, S. Krishnan-Sarin, S. O'Malley, E. Perry, et al. {beta}2-Nicotinic Acetylcholine Receptor Availability During Acute and Prolonged Abstinence From Tobacco Smoking Arch Gen Psychiatry, June 1, 2009; 66(6): 666 - 676. [Abstract] [Full Text] [PDF]

				K. P. Cosgrove, E. M. Mitsis, F. Bois, E. Frohlich, G. D. Tamagnan, E. Krantzler, E. Perry, P. K. Maciejewski, C. N. Epperson, S. Allen, et al. 123I-5-IA-85380 SPECT Imaging of Nicotinic Acetylcholine Receptor Availability in Nonsmokers: Effects of Sex and Menstrual Phase J. Nucl. Med., October 1, 2007; 48(10): 1633 - 1640. [Abstract] [Full Text] [PDF]

				J. K. Staley, S. Krishnan-Sarin, K. P. Cosgrove, E. Krantzler, E. Frohlich, E. Perry, J. A. Dubin, K. Estok, E. Brenner, R. M. Baldwin, et al. Human Tobacco Smokers in Early Abstinence Have Higher Levels of beta2* Nicotinic Acetylcholine Receptors than Nonsmokers. J. Neurosci., August 23, 2006; 26(34): 8707 - 8714. [Abstract] [Full Text] [PDF]