School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
Pharm Res. 2010 May;27(5):933-42. doi: 10.1007/s11095-010-0100-3. Epub 2010 Mar 11.
A novel conjugate, Folate-PEG-CKK(2)-DTPA, was designed and prepared as a carrier for lymphatic metastasized tumor imaging diagnosis and targeting therapy.
Folate-PEG-CKK(2)-DTPA was synthesized and characterized by analysis High Performance Liquid Chromatography, Size Exclusive Chromatography and (1)H-NMR. (99m)Tc-labeled conjugation was prepared, and in vivo quantitative biodistribution and SPECT imaging were studied after subcutaneously injected into the rats and rabbits, respectively. Cell uptake study was carried in a KB cell line using fluorescent methods. In vivo and ex vivo fluorescent imaging study was carried in tumor-bearing nude mouse to evaluate its targeting ability.
Folate-PEG-CKK(2)-DTPA was synthesized with high purity. Both in vivo biodistribution study and SPECT imaging study show the rapid direction and high distribution of the conjugation to the lymph nodes. The uptake of fluorescence-labeled Folate-PEG-CKK(2)-DTPA in human oral epidermis carcinoma cells was observed. In vivo and ex vivo fluorescent imaging study indicated it could accumulate in tumor region after vein tail injection in nude mouse.
All these findings suggested Folate-PEG-CKK(2)-DTPA as a novel and dependable carrier for tumor diagnosis and therapy, especially for lymph-metastasized tumors.
设计并制备一种新型缀合物叶酸-PEG-CKK(2)-DTPA，作为淋巴转移瘤成像诊断和靶向治疗的载体。
通过高效液相色谱、尺寸排阻色谱和（1）H-NMR 分析对叶酸-PEG-CKK(2)-DTPA 进行了合成和表征。（99m）Tc 标记的缀合物进行了制备，并分别在皮下注射到大鼠和兔子后进行了体内定量生物分布和 SPECT 成像研究。使用荧光法进行了 KB 细胞系的细胞摄取研究。在荷瘤裸鼠中进行了体内和体外荧光成像研究，以评估其靶向能力。
叶酸-PEG-CKK(2)-DTPA 的合成纯度较高。体内生物分布研究和 SPECT 成像研究均显示该缀合物迅速向淋巴结方向分布并高分布。观察到人口腔表皮癌细胞中荧光标记的叶酸-PEG-CKK(2)-DTPA 的摄取。静脉尾注裸鼠后，体内和体外荧光成像研究表明其可在肿瘤部位蓄积。
所有这些发现表明，叶酸-PEG-CKK(2)-DTPA 是一种新型、可靠的肿瘤诊断和治疗载体，特别是用于治疗淋巴转移瘤。
