前言: 腫瘤細胞的增生，血管新生(Angiogenesis)扮演著重要的角色。在內皮細胞血管新生時會表現一種細胞粘著分子(CAM)稱之為整合素(Integrin)，其中αvβ3成員在惡性神經膠質瘤(Glioblastoma multiforme)生長期細胞中發現有大量的表現。αvβ3整合素與Argnine-Glycin-Aspartic acid (RGD)序列的胜肽具有高度特異性親和力，RGD已為多數腫瘤治療及診斷之標靶試劑。藥劑傳遞至腦內須通過血腦障壁(BBB)。本研究利用在微氣泡存在下施予低能量超音波短暫打開血腦障壁以易於輸送藥物的技術，探討放射性試劑131I-E[c(RGDyK)]2傳遞至腦腫瘤之效果。
方法: 利用Iodogen放射性碘標誌的方法製備131I-E[c(RGDyK)]2。實驗利用原位神經膠質瘤小鼠模式。將準備妥植有U87MG-fLuc細胞的裸鼠，利用生物冷光造影(BLI)及核磁共振造影(MRI)偵測腫瘤的生長位置及大小。以7T-核磁共振造影(7T-MRI)的影像作腦瘤的定位及偵測體積，再以奈米級單光子發射電腦斷層掃描及電腦斷層掃描造影(nano-SPECT/CT)作動物體內放射試劑131I-E[c(RGDyK)]2 之追蹤造影，並利用PMOD軟體做影像定量融合分析以及自發放射線顯影(Autoradiography)定量分析以確定此放射性試劑傳遞至腦腫瘤之效果。
結果: 131I-E[c(RGDyK)]2放射化學產率可達95%。以BLI及MRI偵測腫瘤生長位置及大小，兩種造影結果具有高度相關性 (R2 = 0.97)。實驗組與控制組動物於給藥前腫瘤大小控制於6.53±3.71 mm3與6.09±4.54 mm3附近。施予聚焦式超音波的實驗組，在給藥0.5小時後的腦腫瘤吸收放射劑量(4.97±0.49 %ID/ml)約為未施予聚焦式超音波的控制組(2.41±0.48 %ID/ml)的2.03±0.32倍。在給藥後24 小時的定量分析，實驗組(2.02±0.25 %ID/ml)大於控制組(0.44±0.02 %ID/ml)的4.57±2.04倍。同時於自發放射線顯影定量分析亦得到類似結果，在給藥0.5小時後施加聚焦式超音波的腫瘤放射累積劑量(4.890±0.510 %ID/ml)為未施予聚焦式超音波的控制組(1.820±0.031 %ID/ml)之2.682±0.279倍。
結論:經由以上實驗驗證放射性試劑131I-E[c(RGDyK)]2在經施加聚焦式超音波，不但能夠增加藥劑傳遞至原位腦腫瘤，而且可能具有延長藥劑停滯腦腫瘤的效果。

Introduction: Angiogenesis plays a critical role in tumor growth. Integrin αVβ3 is a kind of cell adhesion molecule (CAM) that overexpresses on active angiogenic endothelium and glioblastoma cells. The arginine-glycin-aspartic acid (RGD) peptide is recognized to possess specific affinity with integrin αVβ3. The blood-brain barrier (BBB) is an obstacle for drugs for treating and diagnosing CNS diseases. This study utilized focused ultrasound (FUS) of low-energy burst wave in the presence of microbubbles to transiently disrupt the BBB to increase the radiotracer 131I-E[c(RGDyK)]2 delivery to brain tumor.
Methods: U87MG-fLuc glioma-bearing nude mice were prepared. The radiotracer, 131I-E[c(RGDyK)]2 was prepared by iodogen method. Bioluminescence imaging (BLI) and magnetic resonance imaging (MRI) were utilized to measure tumor areas and volumes of the mice. Nano-SPECT/CT imaging was performed after administering the radiotracer into the glioma-bearing mice after sonication with focused ultrasound. Finally, quantitative autoradiography was applied to double confirm the results from fused SPECT and MRI.
Results: 131I-E[c(RGDyK)]2 was obtained in high radiolabeled yield (RCP > 95%). There was a good correlation (R2 = 0.97) between BLI and MRI for monitoring the tumor volumes. The tumor sizes of experimental group and control group were controlled in ranges of 6.534±3.7 and 6.09±4.54 mm3, respectively. By SPECT/CT and MRI analyses, there was 2.03±0.32 fold increase of the tumor uptake comparing FUS (4.97±0.49 %ID/ml) with W/O FUS (2.41±0.48 %ID/ml) at 0.5 h postinjection. The tumor uptake of the FUS treated mice (2.02±0.25 %ID/ml) was found to reach 4.57±2.04 fold increase compared to that of W/O FUS mice (0.44±0.02 %ID/ml) at 24 h postinjection. Autoradiography showed that the accumulation of the radiotracer in the brain tumor of the FUS group (4.890±0.510 %ID/ml) was 2.682±0.279 fold greater than that of the W/O FUS group (1.820±0.031 %ID/ml) at 0.5 h postinjection, which was similar to SPECT/CT and MRI analysis.
Conclusion: This study demonstrated that the focused ultrasound technique to disrupt BBB could enhance and probably prolong the tumor uptake of 131I-E[c(RGDyK)]2.

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