Coincidence Planar Imaging for Dynamic [18F] FDG Uptake in Nude Mice with Tumors and Inflammation: Correlated with Histopathology and Micro-autoradiography

裸鼠腫瘤及發炎模式之動態［氟-18］去氧葡萄糖攝取符時平面造影－組織病理學及微放射自動顯像術之相關對照研究

孫英玲(Ying-Ling Sun) ； 詹美齡(Meei-Ling Jan) ； 高潘福(Pan-Fu Kao) ； 范國賢(Kuo-Hsien Fan) ； 許惠婷(Hui-Ting Hsu) ； 張文震(Wen-Chen Chang) ； 沈永吉(Young-Chi Shen) ； 李德偉(Te-Wei Lee)

《The Kaohsiung Journal of Medical Sciences》 21卷6期 (2005/06) Pp. 258-266

摘要

核能研究所自行研發一部符時偵測儀，可用以進行小鼠正子放射製劑造影之研究，本實驗應用該符時偵測儀進行裸鼠腫瘤及發炎模式的［氟-18］去氧葡萄糖(FDG)藥物動力學研究，以動態連續造影方法觀察FDG在病灶處的攝取模式，以作為研發或測試治療癌症及發炎新藥的研究基礎。應用6隻腫瘤及2隻發炎模式裸鼠，在接受25.9百萬貝克(MBq)的FDG靜脈注射後進行連續4小時的動態攝影。資料經影像處理後，分別圈選病灶及對側大腿以作為計算病灶與背景放射活性的比值，當比值達到穩定時即定義為平衡狀態。所有裸鼠的病灶均接受組識學切片檢查，有6隻裸鼠的病灶並進行微放射自動顯像術檢查。在藥物動力學方面，FDG在腫瘤及發炎病灶都在注射後三小時達到平衡狀態。腫瘤與背景放射活性的比值在2.0-4.0之間，發炎病灶在第四天及第八天的病灶與背景放射活性的比值分別為2.3及5.5。組識學切片顯示巨嗜細胞及中性白血球在腫瘤周圍及發炎病灶浸潤現象。顯微自動放射顯像術顯示有明顯銀染沉積現象。本研究顯示應用符時偵測儀可以決定裸鼠腫瘤及發炎模式的FDG最適切造影時間為靜脈注射後3小時。本研究映證應用動態連續造影方法可觀察未來新治療藥物處理後的FDG攝取變化的追蹤反應。

關鍵字

［氟-18］去氧葡萄糖 ； 裸鼠 ； 動態符時平面造影

並列摘要

The Institute of Nuclear Energy Research of Taiwan has developed a dynamic coincidence detection device for positron emitted radiotracer pharmacodynamic study in small mice models. In this study, we set up an experimental paradigm by determining [fluorine-18]-2-deoxy-2-fluoro-D-glucose ([18F]FDG) dynamic uptake in tumors and inflammations in nude mice as the foundation for future applications in therapy development. Histopathology and micro-autoradiography of these tumors and inflammations were obtained for confirmation. Dynamic coincidence planar images of six tumors and two inflammations in nude mice were acquired over 4 hours immediately after injection of 25.9 MBq of [18F]FDG into the right thigh of each animal. After image reconstruction, the lesion-to-background ratios were calculated in regions of interest over the lesion and contralateral thigh to determine the equilibrium status of the radiotracer. All mice were sacrificed for histopathologic examination and six of the mice were examined with micro-autoradiography. [18F]FDG uptake in tumors and inflammations both reached equilibrium about 3 hours after injection. At equilibrium, [18F]FDG uptake into tumors was two to four times higher than the background. Uptake into the 4-day and 8-day inflammations was 2.3 and 5.5 times higher than the background, respectively. Histopathology showed macrophage and neutrophil infiltration around the tumors and in the inflammations. Micro-autoradiography showed dense silver grains in the granulation tissue surrounding the tumors and inflammations. The preliminary results suggested that dynamic [18F]FDG coincidence planar imaging can help in determining the suitable time for static [18F]FDG imaging in nude mice models. The optimal time for static [18F]FDG positron emission tomography imaging was around 3 hours after injection. The paradigm for determining a dynamic [18F]FDG uptake pattern was demonstrated for future new therapeutic drug experimental use.

並列關鍵字

[fluorine-18]-2-deoxy-2-fluoro-D-glucose ； nude mice ； dynamic coincidence planar image