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  • Title: [Folate-poly-L-lysine-Gd-DTPA as MR contrast agent for tumor imaging via folate receptor-targeted delivery].
    Author: Yuan Z, Liu SY, Xiao XS, Zhong GR, Jiang QJ.
    Journal: Zhonghua Yi Xue Za Zhi; 2007 Mar 13; 87(10):673-8. PubMed ID: 17553304.
    Abstract:
    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, GdCl(3) 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 with that observed before injection at 0.5 hour and 3 hours, the biggest difference appeared at 0.5 hour; The muscle signal intensity at 0.5 hour time-point showed statistically difference with that observed before injection. CONCLUSION: Folate-PL-Gd-DTPA could be combined to tumor cells appetencially via folate receptor and significantly targeted to tumor cells with rich folate receptors for MR imaging.
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