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 Fujimura, Y. Articles by Ito, H. Search for Related Content PubMed PubMed Citation Articles by Fujimura, Y. Articles by Ito, H.

Quantitative Analyses of ¹⁸F-FEDAA1106 Binding to Peripheral Benzodiazepine Receptors in Living Human Brain

¹ Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan; ² Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; ³ Clinical Neuroscience, Medical Sciences for Control of Pathological Processes, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan; ⁴ Department of Medical Imaging, National Institute of Radiological Sciences, Chiba, Japan; and ⁵ SHI Accelerator Service Co. Ltd., Tokyo, Japan

Correspondence: For correspondence or reprints contact: Tetsuya Suhara, MD, PhD, Brain Imaging Project, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inage-ku, Chiba, 263-8555, Japan. E-mail: suhara{at}nirs.go.jp

N-(5-Fluoro-2-phenoxyphenyl)-N-(2-¹⁸F-fluoroethyl-5-methoxybenzyl)acetamide (¹⁸F-FEDAA1106) is a potential PET ligand with highly selective and specific binding to peripheral benzodiazepine receptor (PBR). It has been reported that the regional density of PBR in the brain is increased in several neurodegenerative and psychiatric disorders. Thus, a reliable tracer method for evaluating PBR would be of use clinically and for research. To our knowledge, this is the first study to investigate the ¹⁸F-FEDAA1106 binding to PBR in living human brain by PET. We also aimed to evaluate various analytic methods to quantify the density of PBR. Methods: PET studies with ¹⁸F-FEDAA1106 were performed on 7 healthy men. Volumes of interest (VOIs) were drawn on PET images. In each VOI, binding potential (BP) was calculated by nonlinear least-squares (NLS) fitting based on the 2-tissue compartment model, and the distribution volume (DV) was also estimated by NLS, Logan plot, and multilinear analysis (MA) methods. To estimate errors in calculation of BP and DV, simulation studies were also performed. Results: The DVs estimated with each of the methods were significantly correlated. There was also significant correlation between BP with NLS and DV with NLS, Logan plot, or MA. But the interindividual differences in the distribution volume of the free and nonspecific binding compartment (K₁/k₂) were relatively large. In a simulation study, variation of the DV estimated by Logan plot was relatively small, but it was underestimated as the noise increased. By MA, the bias of DV was smaller, but the variation of DV was larger than by Logan plot. Within a 3% noise level, there was almost no difference between Logan plot and MA in both bias and variation. DVs estimated by both Logan plot and MA were underestimated by 10%–20%. Although the variation of DV was larger by NLS than by Logan plot, it was small enough in the noise level of VOI analysis, and the bias of DV was 0%–2%. Conclusion: The simulation studies indicated that NLS is a suitable method for the estimation of ¹⁸F-FEDAA1106 binding to PBRs.

Key Words: ¹⁸F-FEDAA1106 • microglia • peripheral benzodiazepine receptor • binding potential • PET

This article has been cited by other articles:

				Y. Fujimura, S. S. Zoghbi, F. G. Simeon, A. Taku, V. W. Pike, R. B. Innis, and M. Fujita Quantification of Translocator Protein (18 kDa) in the Human Brain with PET and a Novel Radioligand, 18F-PBR06 J. Nucl. Med., July 1, 2009; 50(7): 1047 - 1053. [Abstract] [Full Text] [PDF]

				M. Miyoshi, H. Ito, R. Arakawa, H. Takahashi, H. Takano, M. Higuchi, M. Okumura, T. Otsuka, F. Kodaka, M. Sekine, et al. Quantitative Analysis of Peripheral Benzodiazepine Receptor in the Human Brain Using PET with 11C-AC-5216 J. Nucl. Med., July 1, 2009; 50(7): 1095 - 1101. [Abstract] [Full Text] [PDF]

				B. Ji, J. Maeda, M. Sawada, M. Ono, T. Okauchi, M. Inaji, M.-R. Zhang, K. Suzuki, K. Ando, M. Staufenbiel, et al. Imaging of Peripheral Benzodiazepine Receptor Expression as Biomarkers of Detrimental versus Beneficial Glial Responses in Mouse Models of Alzheimer's and Other CNS Pathologies J. Neurosci., November 19, 2008; 28(47): 12255 - 12267. [Abstract] [Full Text] [PDF]

				M. L. James, R. R. Fulton, J. Vercoullie, D. J. Henderson, L. Garreau, S. Chalon, F. Dolle, S. Selleri, D. Guilloteau, and M. Kassiou DPA-714, a New Translocator Protein-Specific Ligand: Synthesis, Radiofluorination, and Pharmacologic Characterization J. Nucl. Med., May 1, 2008; 49(5): 814 - 822. [Abstract] [Full Text] [PDF]

				A. K. Brown, M. Fujita, Y. Fujimura, J.-S. Liow, M. Stabin, Y. H. Ryu, M. Imaizumi, J. Hong, V. W. Pike, and R. B. Innis Radiation Dosimetry and Biodistribution in Monkey and Man of 11C-PBR28: A PET Radioligand to Image Inflammation J. Nucl. Med., December 1, 2007; 48(12): 2072 - 2079. [Abstract] [Full Text] [PDF]

				M.-R. Zhang, K. Kumata, J. Maeda, K. Yanamoto, A. Hatori, M. Okada, M. Higuchi, S. Obayashi, T. Suhara, and K. Suzuki 11C-AC-5216: A Novel PET Ligand for Peripheral Benzodiazepine Receptors in the Primate Brain J. Nucl. Med., November 1, 2007; 48(11): 1853 - 1861. [Abstract] [Full Text] [PDF]

				H. Boutin, F. Chauveau, C. Thominiaux, M.-C. Gregoire, M. L. James, R. Trebossen, P. Hantraye, F. Dolle, B. Tavitian, and M. Kassiou 11C-DPA-713: A Novel Peripheral Benzodiazepine Receptor PET Ligand for In Vivo Imaging of Neuroinflammation J. Nucl. Med., April 1, 2007; 48(4): 573 - 581. [Abstract] [Full Text] [PDF]