α_vβ_3受体显像剂^(99)Tc^m(N)(PNP6)(Cys-RGD)的制备及动物实验

Preparation and Biological Study of ^(99)Tc^m(N)(PNP6)(Cys-RGD) for Integrin α_vβ_3-positive Tumor Imaging

为探讨99Tcm标记的小分子环形Cys-RGD肽用于αvβ3受体阳性肿瘤显像的可行性,以99Tcm(N)核联合协同配体二膦基胺类化合物二[二(乙氧基丙基膦)-乙基]-乙氧基乙基胺(PNP6)对环形Cys-RGD肽(c(Arg-Gly-Asp-D-Tyr-Lys)-Cys)进行了标记,并考察了标记物的体外稳定性及正常小鼠和荷FWK-1胰腺癌裸鼠模型的体内生物分布和平面显像。标记条件经优化后,标记率大于92%,且具有良好的体外稳定性。生物分布实验表明,99Tcm(N)(PNP6)(Cys-RGD)在血液中清除较快,主要通过肾脏排泄;注药后1h标记物在肿瘤中的摄取值为2.92±0.71%/g,注药后4h肿瘤与血和肿瘤与肌肉的放射性摄取比(T/NT)分别为11.0和3.1;注药后1h,肿瘤显像清晰。以上结果提示,99Tcm(N)(PNP6)(Cys-RGD)有望成为αvβ3受体阳性肿瘤显像剂。

The Cys-RGD peptide is labelled with ^99Tc^m-nitrido core combined with PNP6 ligand （PNP6 = bis （diethoxypropylphosphino ethyl） ethoxy ethylamine） to investigate the possibility of radiolabelled RGD peptides for tumor αvβ3 integrin receptor scintigraphy. The radiochemical purity is measured with HPLC, the in vitro stability is investigated at room temperature and at 37 ℃ incubated in the cystein and serum solution. Biodistribution studies and gamma camera imaging are performed in normal mice and nude mice bearing FWK-1 pancreatic tumor xenografts. More than 92% radiolabelling yield is achieved under optimized condition. The high in vitro stability is found for ^99Tc^m （N）（PNP6）（Cys-RGD）. In vivo biodistribution studies indicate the radiolabelled peptide is cleared rapidly from blood and mainly excreted via urinary system. Tumor uptake is 2.92±0.71% /g at 1 h after injection. The uptake ratios of tumor to blood and tumor to muscle （T/NT） are 11.0 and 3. 1 at 4 h after injection, respectively. Scintigraphic imaging allows contrasting visualisation of αvβ3-expressed tumors at 1 h after injection. The results suggest ^99Tc^m （N）（PNP6）（Cys- RGD） may be the potential agent for αvβ3-positive tumor imaging.