肿瘤血管靶向分子探针多肽RRL(g2)的作用研究

Technetium-99m-Arg-Arg-Leu(g2):A Modified Peptide Probe Targeted to Neovascularization in Molecular Tumor Imaging

[目的]设计合成分子结构更小的多肽RRL(g2),并用放射性核素99mTc标记,得到新型优化肿瘤新生血管分子探针。[方法]应用化学合成法合成多肽RRL(g2)及对照肽片段GGG(g2),应用高效液相色谱(HPLC)及电喷雾离子质谱(EMI-MS)对合成化合物的分子量及纯度进行鉴定,进而对放射性核素99mTc标记的RRL(g2)多肽探针及对照肽进行体内外生物学性质评价。[结果]应用化学合成法合成的RRL(g2)及GGG(g2)纯度达99%以上,放射性核素99mTc的标记率约73%,稳定性较好。静脉注射分子探针后30min,99mTc-RRL(g2)相对于对照肽99mTc-GGG(g2),在肿瘤组织中有较高的摄取率,而且在肿瘤组织中能滞留较长时间。[结论]新型肿瘤新生血管多肽探针99mTc-RRL(g2)相比于131I-tRRL,在肿瘤新生血管分子显像应用中拥有更大的优势,如肿瘤摄取率的增加,是更有前景的新型肿瘤新生分子显像多肽探针。

[Purpose] To develop smaller structure cyclic RRL（g2） and radiolabeled with 99mTc as a novel and optimized peptide probe on tumor angiogenesis molecular imaging.[Methods] Both RRL（g2） and control peptide GGG（g2） peptide chains were synthesized and characterized by HPLC and EMI-MS analysis.After synthesized and purified,the peptides were radiolabeled with 99mTc by a one-step method for physicochemical property assay and biodistribution experiments.[Results] The purity of peptide RRL（g2） and GGG（g2） were more than 99% after synthesized and purified.The radiolabeling of 99mTc-RRL（g2） has reached 73% and it is stable in vitro.99mTc-RRL（g2） had higher tumor uptake（30min after injection） and longer tumor retention than 99mTc-GGG（g2） in tumor models tested.[Conclusions] The 99mTc-RRL（g2） has more good characteristics such as higher tumor uptake radio and short halflife-time compared with 131I-tRRL.The information obtained here may guide the future development of RRL peptide-based tumor angiogenesis molecular imaging and internal radiotherapeutic agents targeting tumor neavascular.