title: Evaluation of simplified kinetic analyses for measurement of brain acetylcholinesterase activity using N-[11C]Methylpiperidin-4-yl propionate and positron emission tomography.
abstract: The applicability of two reference tissue-based analyses without arterial blood sampling for the measurement of brain regional acetylcholinesterase (AChE) activity using N-[11C]methylpiperidin-4-yl propionate ([11C]MP4P) was evaluated in 12 healthy subjects. One was a linear least squares analysis derived from Blomqvist's equation, and the other was the analysis of the ratio of target-tissue radioactivity relative to reference-tissue radioactivity proposed by Herholz and coworkers. The standard compartment analysis using arterial input function provided reliable quantification of k3 (an index of AChE activity) estimates in regions with low (neocortex and hippocampus), moderate (thalamus), and high (cerebellum) AChE activity with a coefficient of variation (COV) of 12% to 19%. However, the precise k3 value in the striatum, where AChE activity is the highest, was not obtained. The striatum was used as a reference because its time-radioactivity curve was proportional to the time integral of the arterial input function. Reliable k3 estimates were also obtained in regions with low-to-moderate AChE activity with a COV of less than 21% by striatal reference analyses, though not obtained in the cerebellum. Shape analysis, the previous method of direct k3 estimation from the shape of time-radioactivity data, gave k3 estimates in the cortex and thalamus with a somewhat larger COV. In comparison with the standard analysis, a moderate overestimation of k3 by 9% to 18% in the linear analysis and a moderate underestimation by 2% to 13% in the Herholz method were observed, which were appropriately explained by the results of computer simulation. In conclusion, simplified kinetic analyses are practical and useful for the routine analysis of clinical [11C]MP4P studies and are nearly as effective as the standard analysis for detecting regions with abnormal AChE activity.
authors.affiliation: Department of Medical Imaging, National Institute of Radiological Sciences, Chiba University, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukushi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shinotoh
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nagatsuka
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Akiyo
authors.initials: A
authors.lastname: Aotsuka
authors.forename: Tsuneyoshi
authors.initials: T
authors.lastname: Ota
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Shuji
authors.initials: S
authors.lastname: Tanada
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Irie
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism* / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D008875:Middle Aged; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism*; D011422:Propionates / Q000737:chemistry / Q000378:metabolism*; D011849:Radioactive Tracers; D012016:Reference Values; D013223:Statistics as Topic; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D002250:Carbon Radioisotopes; C100519:N-methyl-4-piperidyl propionate; D010880:Piperidines; D011422:Propionates; D011849:Radioactive Tracers; D000110:Acetylcholinesterase