18F-fluorodeoxyglucoseと14C-iodoantipyrineを用いた定量的二重標識オートラディオグラフィー

QUANTITATIVE DOUBLE TRACER AUTORADIOGRAPHIC TECHNIQUE FOR SIMULTANEOUS MEASUREMENT OF LCBF AND LCGU USING 14C-IAP AND 18F-FDG

　抄録　¹⁸F-fluorodeoxyglucose （FDG）と¹⁴C-iodoantipyrine （IAP）を用いて，局所脳グルコース利用率（LCGU）と局所脳血流（LCBF）を同時に定量的に測定できる二重標識オートラディオグラフィーについて報告した。測定は覚醒正常ラットおよび左中大脳動脈（MCA）閉塞ラットで行った。露光開始時の¹⁸F-FDGの組織濃度が¹⁴C-IAPの50倍以上であれば¹⁸F-FDG像における¹⁴Cのcross contaminationは生理的状態では2％以下で，病的状態においても無視できるものであった。この二重標識オートラディオグラフィーではコンピューターを用いたイメージアナライザーによりLCGU／LCBF比の像を得ることができ，正常ラットではその値は76±8％μmol／mlでMCA閉塞3時間後には約2〜3倍に上昇しその約50％は嫌気性解糖が行われていることが示された。この方法は単にグルコース利用率と脳血流の同時測定のみならず，現在市販されている¹⁴Cでラベルされたトレーサーを用い¹⁸F化合物と組み合わせ，いろいろなパラメーターを同時に測定できる可能性を示した。

We have reported a quantitative double tracer autoradiographic technique for the simultaneous measurement of local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) using ¹⁴C-IAP and ¹⁸F-FDG respectively.

Six awake normal rats and 3 left middle cerebral artery (MCA) occluded rats were used for this experiments. A 50-hold greater radioactivity of ¹⁸F was administered and the first exposure was done for 2 hours to obtain a ¹⁸F image. Three days later (39 half-lives of ¹⁸F), a second exposure was done for 5 to 6 days to obtain the ¹⁴C image. Tissue concentration of ¹⁴C was measured relative to the commercially available ¹⁴C-methyl metha-crylate standards. ¹⁸F standards were prepared in each experiment. Cross contamination of ¹⁴C in the first exposure was less than 2% in the normal state and less than 4% even in the uncoupling condition. The values obtained by this methods for LCBF and LCGU agreed closely with thoseobtained by a single tracer technique preveously reported in the literature.

The technique outlined in this paper also pro-vided local glucose utilization flow ratio (LGFR) for the first time. LGFR was obtained by dividing the LCGU image by LCBF image and was express-ed as percent μmol/ml. The mean LGFR of cont-rol rats was 76±8% gmol/m/. In a MCA occlusion group, LGFR of ischemic cortex increased until 2 to 3 times higher than that of contralateral non-ischemic cortex. Oxygen glucose index image which was obtained from the LCGU and A-V differences of O₂ showed that approximately half of the glucose was metabolized anerobically. In spite of the fact that we made several assumptions in this study, we believe the present methods to be useful.

The present double tracer autoradiograohic tech-nique using ¹⁸F-FDG and ¹⁴C-IAP is the simplest and most acurate method for measuring LCBF and LCGU described to date. There are many ways to combine not only 18F-FDG and other ¹⁴C-label-led compounds but also other 18F-labelled tracers with ¹⁴C-labelled tracers.