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Titolo:
Kinetic analysis of [C-11]MP4A using a high-radioactivity brain region that represents an integrated input function for measurement of cerebral acetylcholinesterase activity without arterial blood sampling
Autore:
Nagatsuka, S; Fukushi, K; Shinotoh, H; Namba, H; Iyo, M; Tanaka, N; Aotsuka, A; Ota, T; Tanada, S; Irie, T;
Indirizzi:
Natl Inst Radiol Sci, Inage Ku, Chiba 2638555, Japan Natl Inst Radiol SciChiba Japan 2638555 Inage Ku, Chiba 2638555, Japan Chiba Univ, Sch Med, Asahi Neurol Hosp, Chiba 280, Japan Chiba Univ Chiba Japan 280 Sch Med, Asahi Neurol Hosp, Chiba 280, Japan Chiba Univ, Sch Med, Dept Psychiat, Chiba 280, Japan Chiba Univ Chiba Japan 280 niv, Sch Med, Dept Psychiat, Chiba 280, Japan Chiba Univ, Sch Med, Dept Neurol, Chiba 280, Japan Chiba Univ Chiba Japan 280 Univ, Sch Med, Dept Neurol, Chiba 280, Japan Daiichi Pure Chem Co Ltd, ADME TOX Res Inst, Ibaraki, Osaka, Japan DaiichiPure Chem Co Ltd Ibaraki Osaka Japan Inst, Ibaraki, Osaka, Japan Hamamatsu Univ, Sch Med, Dept Neurosurg, Shizuoka, Japan Hamamatsu Univ Shizuoka Japan Sch Med, Dept Neurosurg, Shizuoka, Japan Tokyo Womens Med Coll, Dept Neurosurg, Tokyo 162, Japan Tokyo Womens Med Coll Tokyo Japan 162 , Dept Neurosurg, Tokyo 162, Japan Juntendo Univ, Sch Med, Dept Psychiat, Tokyo 113, Japan Juntendo Univ Tokyo Japan 113 , Sch Med, Dept Psychiat, Tokyo 113, Japan
Titolo Testata:
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
fascicolo: 11, volume: 21, anno: 2001,
pagine: 1354 - 1366
SICI:
0271-678X(200111)21:11<1354:KAO[UA>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; IN-VIVO; DEMENTIA; RAT;
Keywords:
acetylcholinesterase; Alzheimer disease; kinetic analysis; N-[C-11]methylpiperidin-4-yl acetate; positron emission tomography;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Irie, T Natl Inst Radiol Sci, Inage Ku, 9-1,Anagawa 4 Chome, Chiba 2638555, Japan Natl Inst Radiol Sci 9-1,Anagawa 4 Chome Chiba Japan 2638555 apan
Citazione:
S. Nagatsuka et al., "Kinetic analysis of [C-11]MP4A using a high-radioactivity brain region that represents an integrated input function for measurement of cerebral acetylcholinesterase activity without arterial blood sampling", J CEREBR B, 21(11), 2001, pp. 1354-1366

Abstract

N-[C-11]methylpiperidin-4-yl acetate ([C-11]MP4A) is an acetylcholine analog. It has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET). [C-11]MP4A is specifically hydrolyzed by AChE in the bra-in to a hydrophilic metabolite, which is irreversibly trapped locally in thebrain. The authors propose a new method of kinetic analysis of brain AChE activity by PET without arterial blood sampling, that is, reference tissue-based linear least squares (RLS) analysis. In this method, cerebellum or striatum is used as a reference tissue. These regions, because of their high AChE activity, act as a biologic integrator of plasma input function duringPET scanning, when regional metabolic rates of [C-11]MP4A through AChE (k(3); an AChE index) are calculated by using Blomqvist's linear least squaresanalysis. Computer simulation studies showed that RLS analysis yielded k(3) with almost the same accuracy as the standard nonlinear least squares (NLS) analysis in brain regions with low (such as neocortex and hippocampus) and moderately high (thalamus) k(3) values. The authors then applied these methods to [C-11]MP4A PET data in 12 healthy subjects and 26 patients with Alzheimer disease (AD) using the cerebellum as the reference region. There was a highly significant linear correlation in regional k(3) estimates between RLS and NLS analyses (456 cerebral regions, [RLS k(3)] = 0.98 x [NLS k(3)], r = 0.92, P < 0.001). Significant reductions were observed in k(3) estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral neocortices (P < 0.001, single-tailed t-test), and hippocampus (P = 0.012) in patients with AD as compared with controls when using RLS analysis. Meanreductions (19.6%) in these 6 regions by RLS were almost the same as thoseby NTLS analysis (20.5%). The sensitivity of RLS analysis for detecting cortical regions with abnormally low k(3) in the 26 patients with AD (138 of 312 regions, 44%) was somewhat less than NLS analysis (52%), but was greater than shape analysis (33%), another method of [C-11]MP4A kinetic analysis without blood sampling. The authors conclude that RLS analysis is practicaland useful for routine analysis of clinical [C-11]MP4A studies.

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Documento generato il 04/12/20 alle ore 09:39:33