不同标记方法对188^Re－环九肽新型探针靶向三阴性乳腺癌的影响

The effect of c（CGRRAGGSC） labeled with 188Re using different methods on targeting the triple-negative breast cancer

目的探讨不同方法制备的2种188Re－环九肽探针稳定性及其对三阴性乳腺癌的靶向性。方法分别采用直接法（预锡化法）和间接法[标记双功能螯合剂联肼尼克酰胺（HYNIC）]188Re标记环九肽[c（CGRRAGGSC）]，对2种产物分别进行质控与稳定性检测。建立荷MDA－MB－468三阴性乳腺癌裸鼠模型，测定2种标记产物的生物学分布，比较两者肿瘤/正常组织（T/NT）放射性比值，鉴定探针的靶向性及生物学活性。采用两样本t检验分析数据。结果直接法标记的188Re－c（CGRRAGGSC）标记率〉87%，但血清温育2 h后降解率约为40%，荷瘤裸鼠体内2 h时T/NT约为2.82±0.23 （n＝3）；间接法标记的188Re－HYNIC－c（CGRRAGGSC）标记率为61%，血清温育2 h后降解率约为10%，荷瘤裸鼠体内2 h时T/NT约为6.27±0.51 （n＝3），与直接法标记产物差异有统计学意义（t＝2.13，P〈0.05）。结论直接法标记率较间接法高，但稳定性及靶向性略差；间接法制备的188Re－HYNIC－c（CGRRAGGSC）在稳定性及保持生物活性方面有显著优势。

ObjectiveTo prepare 188Re-c（CGRRAGGSC） by different labeling methods, and compare the stability and targeting ability for triple-negative breast cancer （TNBC）.Methods188Re labeled c（CGRRAGGSC） was prepared by direct method （pre-tinning method） and indirect method （the hydrazinonicotinamide （HYNIC） conjugated c（CGRRAGGSC） peptide） respectively. Quality control and stabilities of radiolabeled probes were measured. Nude mice bearing TNBC cells （MDA-MB-468） were established and used for detecting the distribution in vivo. Tumor/non-tumor （T/NT） ratios of radiolabeled probes prepared by direct method and indirect method were compared to certify the targeting ability and biological activity. Two-sample t test was used to analyze the data.ResultsThe labeling rate of 188Re-c（CGRRAGGSC） by direct method was 〉87%, but the serum stability was poor （the degradation rate was about 40% at 2 h）, and the T/NT ratio was 2.82±0.23 （n=3） at 2 h. On the other hand, the labeling rate of 188Re-HYNIC-c（CGRRAGGSC） by indirect method was 61%, while the serum stability was about 10% at 2 h, and T/NT ratio was about 6.27±0.51 （n=3） at 2 h, which was significantly higher （t=2.13, P〈0.05）.ConclusionsThe direct method may have higher labeling rate than the indirect method, but the radiolabeled compound by the direct method has poor stability and tumor targeting ability. 188Re-HYNIC-c（CGRRAGGSC） prepared by indirect method may have remarkable advantages on stability and biological activity.