肝癌早期诊断是提高预后的关键。分子影像学是活体早期诊断的希望。分子探针构建是分子影像的核心。MR/SPECT双模探针因兼有两种成像方式的优点而最具临床价值。当前使用Gd(SPIO)和Tc99m分别作为成像核心组合双模探针有许多缺点，本课题组拟采用独特思路构建一种极具应用前景的单核心小分子双模探针：在前期成功构建Gd类MR探针的基础上，根据同位素化学性质相同的原理，以适合SPECT成像的放射性同位素153Gd替代稳定同位素157Gd作为双模成像核心、以能稳定螯合Gd的大环类配体DOTA为双功能连接剂、以能同SSTR2特异性结合的Octreotide为配体，构成双模探针，选择SSTR2阳性和阴性表达的人BEL-7402细胞系和A549细胞系构建裸鼠双瘤模型，借助专用小动物线圈和3.0T超高场磁共振，以及SPECT成像仪，科学直观地完成受体定量特异性显像，为临床提供肿瘤早期诊断和鉴别诊断新方法。

Early diagnosis for human hepatocelluar carcinoma is crucial to the prognosis. Molecular imaging is promising to early diagnosis for tumor due to its native imaging pattern. Construction of competent probe is the key content to molecular imaging. Multi-modality probe which possessed the imaging abilities of corresponding modality is apparently outweighed the conventional single modality probe and therefore multi-modality probe is more valuable in clinical practice. Among these multi-modality probes, MR/SPECT bimodality probe is becoming prominent and mainstream. However, there are a lot of defects found in currently developed MR/SPECT bimodality probes which almost stationary combinated Gd(SPIO) as MR imaging core and Tc99m as SPECT imaging core, respectively.In view of this, our team aimed to developed a novel low molecular weight of MR/SPECT bimodality probe with single imaging core 153Gadolinium both as MR and SPECT imaging media rooted on the principle that radioactive isotopes have identical chemical properties. Based on the related work that our team has successfully developed a Gd-based MR probe before, we plan to select the molecule somatostatin receptor 2(SSTR2) over-expressed on surface of BEL-7402 human hepatocellular carcinoma cells as the specific imaging target which cound specifically bind to its ligand-octreotide (OCT), conjugate OCT with chemically stable bifuncional cyclic linker DOTA (1,4,7,10-Tetraazacyclododecane), then the compoud chelates with 153Gd just did as stable isotope 157Gd, to obtain a bimadality probe 153Gd-DOTA-Octreotide eventually. The probe will be testified in vitro to further exploit its biological and chemical properties for preparation of in vivo experiments in nude mice bearing both BEL-7402 human hepatocellular carcinoma (SSTR2-positive) and A-549 human non-small cell lung cancer (NSCLC) (SSTR2-negative) in bilateral axillary fossa of the animal. 3.0T high field strenth MR scanner (Ge Healthcare) matched with dedicated coil for small animal and dual head coincidence SPECT scanner are applied to perform the coresponding shares of the experiment. Due to its internal character of single imaging core double functional ability, the construction method and procedure of the probe will be simplified greatly, meamwhile, the tumor will be depicted both quantitatively (SPECT) and in high resolution manner(MR) at the same set so as to eliminate those uncontrollable biases other MR/SPECT bimodality probes can not do before. And it also will obviously show the difference of the two tumors in signal intensity or in radionuclide concentration under the condition of direct viewing in a same mouse as a result of different expression of SSTR2 of the two tumors. This project therefore would provide a novel method to develop multi-modality probe, put forward the development of probe construction, cast light on early diagnosis and differentiation of tumors, and benefit the clinical patients in the near future.

肝癌早期诊断是提高预后的关键。分子影像学是活体早期诊断的希望。分子探针构建是分子影像的核心。MR/SPECT双模探针因兼有两种成像方式的优点而最具临床价值。当前使用Gd(SPIO)和Tc99m分别作为成像核心组合双模探针有许多缺点，本课题组拟采用独特思路构建一种极具应用前景的单核心小分子双模探针：在前期成功构建Gd类MR探针的基础上，根据同位素化学性质相同的原理，以适合SPECT成像的放射性同位素153Gd替代稳定同位素157Gd作为双模成像核心、以能稳定螯合Gd的大环类配体DOTA为双功能连接剂、以能同SSTR2特异性结合的Octreotide为配体，构成双模探针，选择SSTR2阳性和阴性表达的人BEL-7402细胞系和A549细胞系构建裸鼠双瘤模型，借助专用小动物线圈和3.0T超高场磁共振，以及SPECT成像仪，科学直观地完成受体定量特异性显像，为临床提供肿瘤早期诊断和鉴别诊断新方法。主要研究内容分两部分，一是构建分子探针，以Gd为成像核心的MR探针构建成功，尽管构建模式比较简单、高效，但由于Gd同位素来源的问题，具有放射性的152Gd探针构建困难，仍将是后续课题的主要突破方向。另一部分是裸鼠双瘤模型构建，双瘤模型的有点是直观，注射SSTR2特异性对比剂后，理论上二者由于SSTR2表达不同，而直观地产生效果不同的增强模式，因此，再同一个体上只需进行简单的图像对比和测量，就可以验证SSTR2特异性与分子探针结合，但由于SSTR2作为对照的A549细胞系，同时表达SSTR2而导致双侧增强对比减弱，影响实验结果。今后可对A549细胞系进行SSTR2基因敲除后，再进行移植，作为BEL-7402人肝癌细胞的SSTR2阴性对照细胞，非常有希望完成裸鼠双瘤模型分子探针特异性成像，使得课题进一步深入，并且具有更大的实际应用前景。