Yuan Zheng, Li Wen-Tao, Ye Xiao-Dan, Liu Shi-Yuan, Xiao Xiang-Sheng
Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032;
Exp Ther Med. 2012 May;3(5):903-907. doi: 10.3892/etm.2012.504. Epub 2012 Mar 5.
Targeted delivery is a highly desirable strategy for diagnostic imaging due to enhanced efficacy and reduced dosage/toxicity. The need to develop target-specific magnetic resonance imaging (MRI) contrast agents to aid in disease characterization is highly essential. In this study, a specific contrast agent, Gd-DTPA-poly-L-lysine (PL-Gd-DTPA)-folate, was synthesized and evaluated for its efficacy as a targeted agent for the imaging of tumors that overexpress the folate receptor. Folic acid was conjugated to PL-Gd-DTPA via the ε-amino groups. The receptor binding properties of folate-PL-Gd-DTPA were studied in cultured tumor cells that overexpressed the folate receptor. The tumor-selecting properties of folate-PL-Gd-DTPA were then evaluated in BALB/c mice bearing subcutaneously implanted folate receptor-positive tumors. Tissue MR signal intensities were measured at six different time-points. In the in vitro study, the folate-PL-Gd-DTPA was able to bind to these cells, which overexpressed the folate receptor, as with free folic acid. Excellent tumor selectivity was also shown in the animal model; after the success of injection of folate-PL-Gd-DTPA, a maximum intensity increase of 125.4% was observed from pre-injection compared to post-injection images of the tumor at the 48 h time-point. The liver enhancement was non-specific and the muscle signal intensity at any time-point after injection showed no statistical difference with that observed before injection. Folate-PL-Gd-DTPA is a promising, novel receptor-specific MRI contrast agent with potential applications in the imaging of human folate receptor-positive tumors.
由于疗效增强且剂量/毒性降低，靶向递送是诊断成像中非常理想的策略。开发靶向特异性磁共振成像（MRI）造影剂以辅助疾病特征描述的需求至关重要。在本研究中，合成了一种特异性造影剂钆喷酸葡胺-聚-L-赖氨酸（PL-Gd-DTPA）-叶酸，并评估了其作为靶向剂对过表达叶酸受体的肿瘤进行成像的效果。叶酸通过ε-氨基与PL-Gd-DTPA偶联。在过表达叶酸受体的培养肿瘤细胞中研究了叶酸-PL-Gd-DTPA的受体结合特性。然后在皮下植入叶酸受体阳性肿瘤的BALB/c小鼠中评估叶酸-PL-Gd-DTPA的肿瘤选择性特性。在六个不同时间点测量组织MR信号强度。在体外研究中，叶酸-PL-Gd-DTPA能够像游离叶酸一样与这些过表达叶酸受体的细胞结合。在动物模型中也显示出优异的肿瘤选择性；注射叶酸-PL-Gd-DTPA成功后，在48小时时间点，与肿瘤注射前图像相比，观察到最大强度增加了125.4％。肝脏增强是非特异性的，注射后任何时间点的肌肉信号强度与注射前观察到的信号强度无统计学差异。叶酸-PL-Gd-DTPA是一种有前景的新型受体特异性MRI造影剂，在人类叶酸受体阳性肿瘤成像中具有潜在应用价值。
