中文摘要：

目的研究能通过叶酸受体介导靶向叶酸受体阳性肿瘤细胞实现MR肿瘤靶向成像的对比剂叶酸-PL-Gd-DTPA，探讨该试剂MR靶向诊断裸鼠入肺癌模型可行性。方法（1）在碱性条件下聚赖氨酸（poly-L-Lysine，PL）经二乙三胺五酸（DTPA）修饰后，得到大分子载体PL-DTPA，装载Gd^3＋制成大分子对比剂PL-Gd-DTPA，在适宜的反应条件下，连接上叶酸得到肿瘤靶向对比剂叶酸-PL-Gd-DTPA。（2）采用高效液相色谱法（HPLC）测定大分子纯度，高频电感耦合等离子体发射光谱法（ICP-AES）测定Gd^3＋含量，使用细胞叶酸受体竞争结合法证明试剂活性。（3）用人肺腺癌裸鼠模型进行MR成像研究，将动物分成两组，进行MR平扫后，分别经鼠尾静脉注射叶酸-PL-Gd-DTPA、Gd-DTPA试剂后0．5、3、6、14、24、38、48、62和72h行MR扫描，测定各时间点瘤体和肌肉信号强度。结果（1）制备出高纯度叶酸-PL-Gd-DTPA，该多聚体具备与叶酸受体高亲和力结合特性，每分子对比剂载带56个Gd“离子。（2）在肿瘤模型活体MR成像中，瘤体各扫描时间点信号值差异有统计学意义（F=7．82，P=0．0052），平均强化率125．4％。（3）实验组瘤体各时间点信号值差异有统计学意义，强化峰值出现在24-48h时间点，对照组瘤体各扫描时间点信号值差异亦有统计学意义，强化峰值出现在0．5h时间点。实验组肌肉各扫描时间点信号值差异无统计学意义（F=1．86，P=0．0579）。结论叶酸-PL-Gd-DTPA能与叶酸受体高亲和力结合，在活体内能靶向叶酸受体阳性细胞的肿瘤，实现MR靶向诊断。

英文摘要：

Objective To study folate-conjugated Gd-DTPA-Poly-L-Lysine （folate-PL-Gd-DTPA） as MR targeting agent to tumor cells via folate receptor, to evaluate feasibility and effectiveness by observing MR signal variations and imaging feature of pulmonary tumor xenografts in nude mice using this contrast material. Methods （ 1 ） Using Poly-L-Lysine （PL） as linker, after PL was tethered with caDTPA, GdCl3 was added to label DTPA- PL, then PL-Gd-DTPA was conjugated to folate, a specific MR contrast agent, was thus prepared. （2） Using high performance liquid chromatography （HPLC） to evaluate the conjugate purity, and the ICP-AES to test Gd^3＋ concentration, while the activity evaluated by competitive folate receptor binding with folic acid. （3） Folate-PL-Gd-DTPA as specific contrast agents （ study group, n = 6） and Gd-DTPA as non-specific contrast agents （ control group, n = 4） was injected respectively into caudal vein of the nude mice which was pulmonary tumor xenografts as experimental model in the study. MRI was performed with plain scans, enhanced scans at 30 minutes,3 hours ,6 hours, 14 hours,24 hours, 38 hours ,48 hours ,62 hours and 72 hours after the success of injection. Signal intensities of tumors and muscles were measured. Results （ 1 ） folate-PL-Gd-DTPA was successfully synthesized with high affinity to folate receptor and high concentration of Gd^3＋ （56 Gd^3＋/folate ）. （2） folate-PL-Gd-DTPA had an excellent tumor selectivity in pulmonary tumor xenografts in the animal model. After injection, the tumor signal intensity in the study group was significantly higher than that observed before injection; An average intensity increase of 125. 4% was observed from pre-contrast to post-contrast images of the tumor, which was observed at 24-48 hours after injection; The muscle signal intensity at any time-point after injection showed no statistically difference with that observed before injection. In control group, the tumor signal intensity showed statistically difference