Japanese
Title脳内MAO-B活性評価のためのポジトロントレーサーの開発 - その理論的解析と11C-ジメチルフェネチルアミンの評価 -
Subtitle原著
Authors井上修*, 富永俊義*, 福田信男*, 鈴木和年**, 山崎統四郎*
Authors(kana)
Organization*放射線医学総合研究所臨床研究部, **サイクロトロン管理課
Journal核医学
Volume21
Number6
Page671-678
Year/Month1984/6
Article原著
Publisher日本核医学会
Abstract「要旨」メタボリック-トラッピングトレーサーを応用した, 脳内酵素活性のIn Vivoにおける評価法の開発に関して, 簡単なモデル系を用いて考察を加えた. この方法においては目的とする酵素に対する特異性, および, 測定範囲, 感度ともに, RIトレーサーとして用いる基質の酵素化学的性質(Vmax/Km値)により大きく変化することが示された. また測定範囲は, 基質トレーサーの脳内の排泄速度(Kel)にも依存することが分かり, この排泄速度を決める因子として末梢での代謝反応速度が重要であることが分かった. 外部計測値より評価でき得る脳内の酵素活性の変動範囲を0〜αとすると, αの値はVmax/Km値が小さい程大きくなることが判明し, 基質トレーサーを化学修飾することにより, 測定範囲を比較的任意にデザインすることが可能であることが示された. 脳内MAO活性評価のためのトレーサーとして, N, Nジメチルフェネチルアミンを選択し11Cで標識した. 11C-DMPEAはマウスに静注後, 1分で非常に高い脳への移行を認め, 以後比較的長時間脳内に停まった. 投与1時間後の脳放射能は, 1-deprenylによるMAO-Bの阻害に対し, 特異的に著明な減少を示したが, clorgylineによるMAO-Aの阻害に対しては顕著な変化を認めなかった. この放射能の減少は脳内でのトレーサーの11C-ジメチルアミンへの変換率の減少によることが推定される. 阻害実験における投与1時間後における全脳の放射能と残存するMAO-B活性とは良好な対応を示し, 11C-DMPEAが脳内のMAO-B活性の変化を特異的にとらえ得るトレーサーであることが判明した.
Practice臨床医学：一般
KeywordsMetabolic-trapping, Brain, MAO-B Positron tracer.
English
TitleDevelopment of Positron Tracer for in Vivo Estimation of Brain MAO-B Activity : Theoretical Consideration of Metabolic-trapping Tracers and Evaluation of 11C-N, N Dimethylphenylethylamine
SubtitleOriginal Articles
AuthorsOsamu INOUE, Toshiyoshi TOMINAGA, Nobuo FUKUDA, Kazutoshi SUZUKI, Toshio YAMASAKI
Authors(kana)
OrganizationDivision of Clinical Research, National Institute of Radiological Sciences
JournalThe Japanese Journal of nuclear medicine
Volume21
Number6
Page671-678
Year/Month1984/6
ArticleOriginal article
PublisherTHE JAPANESE SOCIETY OF NUCLEAR MEDICINE
Abstract[Summary]In order to develop a suitable radiotracer for the estimation of brain enzyme activity, we performed a theoretical consideration about a principle of metabolic-trapping tracer method using a simplified model. Both the specificity and the measurable range of enzyme activity of this method were found to be much dependent upon the enzymatic properties of substrate-tracer. The measurable range of brain enzyme activity was found to be from zero to the maximum value which was dependent upon two factors; the elimination rate of substrate-tracer from the brain (Kel) and the Vmax/Km value of substrate. The detectable range of changes in enzyme activity can be made wider by using another substrate as a tracer which has a lower Vmax/Km value or larger Kel value. The specificity can be also favorably designed by selection of substrate with various enzymatic or physicochemical properties as a tracer. N, N-dimethylphenylethylamine (DMPEA) was selected as a substrate-tracer for the estimation of brain MAO-B activity. Very high accumulation of radioactivity into mouse brain at 1 min after intravenous injection of 11C-DMPEA, and a long-term retention of radioactivity in the brain were observed. 11C-DMPEA seemed to be metabolized to 11C-dimethylamine by brain MAO, and be trapped by the blood-brain barrier. When various dosage of 1-deprenyl (a specific MAO-B inhibitor) were pretreated, brain radioactivity at 1 hr after injection of 11C-DMPEA significantly decreased in a dosage (1-deprenyl)-dependent way, while pretreatment with clorgyline (a specific MAO-A infibitor) had no effect. This decrease in radioactivity might be due to the decrease of the production rate of labeled metabolite (11C-dimethylamine) in the brain. The relationship between the radioactivity remaining at 1 hr after injection and MAO-B activity remaining in the brain was quite parallel. 11C-DMPEA seems to be a specific radiotracer for the external detection of alterations in MAO-B activity in the brain with a fair sensitivity.
PracticeClinical medicine
KeywordsMetabolic-trapping, Brain, MAO-B Positron tracer.

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