Mika Naganawa1,2, Yuichi Kimura3, Masahiro Mishina4, Yoshitsugu Manabe5, Kunihiro Chihara5, Keiichi Oda1, Kenji Ishii1, Kiichi Ishiwata1. 1. Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Naka, Itabashi, Tokyo, 173-0022, Japan. 2. Japan Society for the Promotion of Science, Tokyo, Japan. 3. Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1, Naka, Itabashi, Tokyo, 173-0022, Japan. ukimura@ieee.org. 4. Neurological Institute, Nippon Medical School Chiba-Hokusoh Hospital, Chiba, Japan. 5. Graduate School of Information Science, Nara Institute of Science and Technology, Nara, Japan.
Abstract
PURPOSE: [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) is a positron-emitting adenosine A(2A) receptor (A2AR) antagonist for visualisation of A2AR distribution by positron emission tomography (PET). The aims of this paper were to use a kinetic model to analyse the behaviour of [(11)C]TMSX in the brain and to examine the applicability of the Logan plot. We also studied the applicability of a simplified Logan plot by omitting metabolite correction and arterial blood sampling. METHODS: The centrum semiovale was used as a reference region on the basis of a post-mortem study showing that it has a negligibly low density of A2ARs. Compartmental analysis was performed in five normal subjects. Parametric images of A2AR binding potential (BP) were also generated using a Logan plot with or without metabolite correction and with or without arterial blood sampling. To omit arterial blood sampling, we applied a method to extract the plasma-related information using independent component analysis (EPICA). RESULTS: The estimated K (1)/k (2) was confirmed to be common in the centrum semiovale and main cortices. The three-compartment model was well fitted to the other regions using the fixed value of K (1)/k (2) estimated from the centrum semiovale. The estimated BPs using the Logan plot matched those derived from compartment analysis. Without the metabolite correction, the estimate of BP underestimated the true value by 5%. The estimated BPs agreed regardless of arterial blood sampling. CONCLUSION: A three-compartment model with a reference region, the centrum semiovale, describes the kinetic behaviour of [(11)C]TMSX PET images. A2ARs in the human brain can be visualised as a BP image using [(11)C]TMSX PET without arterial blood sampling.
PURPOSE:[7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) is a positron-emitting adenosine A(2A) receptor (A2AR) antagonist for visualisation of A2AR distribution by positron emission tomography (PET). The aims of this paper were to use a kinetic model to analyse the behaviour of [(11)C]TMSX in the brain and to examine the applicability of the Logan plot. We also studied the applicability of a simplified Logan plot by omitting metabolite correction and arterial blood sampling. METHODS: The centrum semiovale was used as a reference region on the basis of a post-mortem study showing that it has a negligibly low density of A2ARs. Compartmental analysis was performed in five normal subjects. Parametric images of A2AR binding potential (BP) were also generated using a Logan plot with or without metabolite correction and with or without arterial blood sampling. To omit arterial blood sampling, we applied a method to extract the plasma-related information using independent component analysis (EPICA). RESULTS: The estimated K (1)/k (2) was confirmed to be common in the centrum semiovale and main cortices. The three-compartment model was well fitted to the other regions using the fixed value of K (1)/k (2) estimated from the centrum semiovale. The estimated BPs using the Logan plot matched those derived from compartment analysis. Without the metabolite correction, the estimate of BP underestimated the true value by 5%. The estimated BPs agreed regardless of arterial blood sampling. CONCLUSION: A three-compartment model with a reference region, the centrum semiovale, describes the kinetic behaviour of [(11)C]TMSX PET images. A2ARs in the human brain can be visualised as a BP image using [(11)C]TMSX PET without arterial blood sampling.
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