Schneider G, Seidel R, Uder M, Wagner D, Weinmann H J, Kramann B
Department of Diagnostic Radiology, University Hospital, Homburg/Saar, Germany.
Invest Radiol. 2000 Sep;35(9):564-70. doi: 10.1097/00004424-200009000-00008.
The extravasation properties of two macromolecular MR imaging contrast media (CM) in relation to structural differences of the terminal vascular bed were investigated to determine whether differentiation between normal (physiological) and tumor (pathological) tissue can be achieved by means of extravasation characteristics.
Gd-DTPA-polylysine (50 kD, CM1) and Gd-DOTA cascade polymer (Gadomer 17; 20 kD, CM2) were labeled with fluorescein isothiocyanate (FITC) to enable in vivo fluorescence microscopy of the microcirculation. After implantation of a dorsal skinfold chamber and 7 days (range, 6-8) after induction of an amelanotic melanoma (A-Mel-3), 14 male hamsters weighing 85 g (range, 70-95 g) received 200 micromol/kg of CM1 by intravenous injection into the jugular vein. CM2 was similarly investigated after an interval of 24 hours. Fluorescence microscopy was performed in areas of subcutaneous tissue, striated muscle, and tumor tissue. Microscopic images were registered by a charge-coupled-device video camera and transferred to a video system. Distribution intensities of CM were evaluated on a digitally based measurement system. A control investigation was performed with FITC-dextran (150 kD).
Gd-DTPA-polylysine showed no extravasation into physiological tissue for the first 10 minutes after injection. After this period, however, the first signs of leakage became apparent. Gd-DOTA cascade polymer was extravasated after 5 minutes into the tumor-free tissue. In tumor capillaries, Gd-DTPA-polylysine could be detected in the extravasal space as well as in physiological tissue after 15 minutes. After injection of Gd-DOTA cascade polymer, direct leakage from tumor capillaries was observed, with a contrast maximum between tumor and surrounding tissue occurring 3 to 5 minutes after CM injection. Good delineation of tumor vascularization from striated muscle and subcutaneous tissue was achieved.
The CM studied showed different microvascular permeation properties. Faster leakage of Gd-DOTA cascade polymer was observed in areas with neoplastic tumor vessels, whereas extravasation in physiological tissue was detected after a period of 5 minutes. Gd-DTPA-polylysine demonstrated nonspecific leakage at later time points.
研究两种大分子磁共振成像造影剂（CM）的外渗特性与终末血管床结构差异的关系，以确定能否通过外渗特征实现正常（生理）组织与肿瘤（病理）组织的区分。
用异硫氰酸荧光素（FITC）标记钆-二乙三胺五乙酸-聚赖氨酸（50kD，CM1）和钆-多胺大环配体级联聚合物（Gadomer 17；20kD，CM2），以便对微循环进行体内荧光显微镜观察。在植入背部皮褶小室并诱导无黑色素黑色素瘤（A-Mel-3）7天（范围6-8天）后，14只体重85g（范围70-95g）的雄性仓鼠经颈静脉静脉注射200μmol/kg的CM1。24小时后以同样方式研究CM2。在皮下组织、横纹肌和肿瘤组织区域进行荧光显微镜检查。通过电荷耦合器件摄像机记录显微图像并传输到视频系统。在基于数字的测量系统上评估CM的分布强度。用FITC-葡聚糖（150kD）进行对照研究。
钆-二乙三胺五乙酸-聚赖氨酸在注射后的前10分钟内未渗入生理组织。然而，在此之后，渗漏的最初迹象变得明显。钆-多胺大环配体级联聚合物在5分钟后渗入无肿瘤组织。在肿瘤毛细血管中，15分钟后在血管外间隙以及生理组织中均可检测到钆-二乙三胺五乙酸-聚赖氨酸。注射钆-多胺大环配体级联聚合物后，观察到肿瘤毛细血管直接渗漏，在注射CM后3至5分钟肿瘤与周围组织之间的对比度达到最大值。实现了肿瘤血管与横纹肌和皮下组织的良好区分。
所研究的CM显示出不同的微血管渗透特性。在肿瘤血管区域观察到钆-多胺大环配体级联聚合物更快渗漏，而在5分钟后检测到其渗入生理组织。钆-二乙三胺五乙酸-聚赖氨酸在后期显示出非特异性渗漏。
