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 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 Mamede, M. Articles by Saji, H. Search for Related Content PubMed PubMed Citation Articles by Mamede, M. Articles by Saji, H.

Quantification of Human Nicotinic Acetylcholine Receptors with ¹²³I-5IA SPECT

¹ Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, Kyoto, Japan
² Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan
³ Brain Function Imaging Division, Human Brain Research Center, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain, especially the ₄ß₂ subtype of nAChR. The cholinergic systems have roles in various neurophysiologic functions, such as learning, memory, and cognition, whereas normal aging and neurodegenerative diseases have been associated with changes in nAChRs. Recently, 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA) has been synthesized as a radioligand for imaging nAChRs with SPECT. ¹²³I-5IA shows higher affinity toward the nAChR ₄ß₂ subtype, enhanced receptor subtype selectivity, good safety, and low nonspecific binding. Methods: In this study, a SPECT quantitative study of human nAChRs binding with ¹²³I-5IA was conducted in healthy volunteers. An arterial input function was obtained for each subject and a 2-compartment model was used to determine the kinetic parameters of ¹²³I-5IA using data from a 6-h scan. The distribution volume (V_T) (mL/mL), which is related to the number of unoccupied binding sites in the brain, was calculated and values were compared with results of a graphical analysis (Logan plot, V_LG). Results: Analysis of the unmetabolized compound showed a high parent fraction of ¹²³I-5IA in plasma. The results from the 2-compartment model analysis showed high V_T values for the thalamus; moderate values for the brain stem, cerebellum, and basal ganglia; and low values for the cortical regions. Good agreement was observed between V_T values and results of autoradiographic experiments done in vitro for nAChR density in human brain. A high correlation index was observed between distribution volumes from model and graphical analyses. Conclusion: Our results indicated that ¹²³I-5IA SPECT is suitable for the quantification of nAChRs in human brain.

Key Words: 5-¹²³I-iodo-3-(2(S)-azetidinylmethoxy)pyridine • SPECT • nicotinic acetylcholine receptors • human brain • distribution volume • quantitative measurement • Logan plot • compartmental model analysis

Related articles in JNM:

THIS MONTH IN JNM

JNM 2004 45: 8A-9A. [Full Text]  

This article has been cited by other articles:

				S J Colloby, S Pakrasi, E K Perry, S L Pimlott, D J Wyper, E D Williams, I G McKeith, and J T O'Brien The effects of donepezil on nicotinic receptor status in dementia: a 123I-5IA-85380 SPECT study J. Neurol. Neurosurg. Psychiatry, April 1, 2008; 79(4): 485 - 487. [Full Text] [PDF]

				K HERHOLZ, S F CARTER, and M JONES Positron emission tomography imaging in dementia Br. J. Radiol., December 1, 2007; 80(Special_Issue_2): S160 - S167. [Abstract] [Full Text] [PDF]

				M. Mamede, K. Ishizu, M. Ueda, T. Mukai, Y. Iida, H. Kawashima, H. Fukuyama, K. Togashi, and H. Saji Temporal Change in Human Nicotinic Acetylcholine Receptor After Smoking Cessation: 5IA SPECT Study J. Nucl. Med., November 1, 2007; 48(11): 1829 - 1835. [Abstract] [Full Text] [PDF]

				J T O'Brien, S J Colloby, S Pakrasi, E K Perry, S L Pimlott, D J Wyper, I G McKeith, and E D Williams {alpha}4{beta}2 nicotinic receptor status in Alzheimer's disease using 123I-5IA-85380 single-photon-emission computed tomography J. Neurol. Neurosurg. Psychiatry, April 1, 2007; 78(4): 356 - 362. [Abstract] [Full Text] [PDF]

				J. K. Staley, C. H. van Dyck, D. Weinzimmer, E. Brenner, R. M. Baldwin, G. D. Tamagnan, P. Riccardi, E. Mitsis, and J. P. Seibyl 123I-5-IA-85380 SPECT Measurement of Nicotinic Acetylcholine Receptors in Human Brain by the Constant Infusion Paradigm: Feasibility and Reproducibility J. Nucl. Med., September 1, 2005; 46(9): 1466 - 1472. [Abstract] [Full Text] [PDF]