^131Ⅰ-NGR-γ显像及切伦科夫光学显像用于肿瘤显像的实验研究

Experiment study of Cerenkov luminescence imaging and gamma scintigraphy with ^131Ⅰ-NGR in tumor

【摘要】目的比较肿瘤^131Ⅰ-NGR-γ显像及切伦科夫光学显像（CLI）的特征与差异，探讨肿瘤多模态显像的有效方法。方法检测并比较小鼠腹腔注射不同活度（0、740kBq及7-4MBq）^131Ⅰ时，体表185kBq及1．85MBq^131Ⅰ的γ显像与CLI信号；γ显像及CLI检测不同活度（0、231、463、925和1850kBq）^131Ⅰ-NGR与CD13表达阳性的HT1080细胞及表达阴性的HP29细胞的结合情况；对荷瘤裸鼠在尾静脉注射18．5MBq^131Ⅰ-NGR后2、4、8及12h进行动态^y显像与CLI，12h后切除体表肿瘤并移植至腹腔，再次进行1显像与CLI。结果γ显像及CLI均能清晰显示体表185kBq及1．85MBq的^131Ⅰ；但随腹腔注射^131Ⅰ的增加.γ显像显示的体表^131Ⅰ信号逐步减弱。当腹腔注射7．4MBq^131Ⅰ时，体表185kBq^131Ⅰ难以显示，而体表1．85MBq^131Ⅰ则仍可显示，但信号明显减低；CLI对体表^131Ⅰ的检测则几乎不受腹腔^131Ⅰ的影响，腹腔注射7．4MBq^131Ⅰ仍可清晰显示体表^131Ⅰ。1显像及CLI均显示CD13受体表达阳性的HT10180细胞与^131Ⅰ-NGR特异结合，而阴性表达的HP29细胞不与^131Ⅰ-NGR结合，且HT10180细胞与^131Ⅰ-NGR的结合随^131Ⅰ-NGR的增加而增加。荷瘤裸鼠注射18．5MBq^131Ⅰ-NGR后2hCLI可清晰显示肿瘤，12h1显像显示肿瘤；12h切除肿瘤移植至腹腔，γ显像清晰显示肿瘤，但CLI却无显示。结论CLI与1显像对肿瘤的显像存在差异。CLI对体表肿瘤的早期检测较好，而核素显像对深部肿瘤的检测较好，两者联合的多模态显像有助于提高对肿瘤的检测。

Objective To compare the＇differences and characteristics between Cerenkov lumines- cence imaging （CLI） and gamma scintigraphy with ^131Ⅰ-NGR in tumor imaging and to evaluate an effective method for imaging tumor by combining both techniques. Methods （1） The ^131Ⅰ sources with radioactivity of 185 kBq and 1.85 MBq were placed at the chest skin surface of 4 mice. CLI and gamma scintigraphy of the surface sources were performed at different peritoneal background by intraperitoneal injection of with dif- ferent radioactivities （0 kBq, 740 kBq and 7.4 MBq）. （2） The uptakes of ^131Ⅰ-NGR under various radioac- tivities （0, 231, 463, 925, 1850 kBq） in CD13-positive HT1080 cells and CD13-negative HP29 cells were evaluated by CLI and gamma scintigraphy. The multi-phase imaging of CLI and gamma scintigraphy for the tumor bearing nude mice was acquired at 2, 4, 8 and 12 h after injection of 18.5 MBq ^131Ⅰ-NGR. The tumor was resected and implanted at peritoneum for CLI and gamma scintigraphy 12 h post-injection. Results （1） Both CLI and gamma scintigraphy were able to clearly visualize surface sources with radioactivities of 185 kBq and 1.85 MBq. However, the signal on gamma scintigraphy decreased with increased radioactivity in peritoneal cavity. When the peritoneal cavity was injected with 7.4 MBq, the surface source of 185 kBqcould not be identified and the source of 1.85 MBq was greatly underestimated. However, Cerenkov signals were less affected by the background activity of peritoneal cavity. Both sources of 185 kBq and 1.85 MBq could be clearly visualized under the background of 7.4 MBq. （2） Both gamma scintigraphy and CLI could show CD13-positive HT1080 cells and were negative for CD13-negative HP29 cells. The higher the dose of ^131Ⅰ- NGR was, the binding with HT1080 cells was more. Subcutaneous tumors could be clearly identified at 2 h by CLI after injection of 18.5 MBq ^131Ⅰ-NGR, but could only be clearly detected by gamma scintigraphy at 12 h. When the tumor was resected and implanted in peritoneal cavity, it could only be detected by gamma scintigraphy. Conclusions CLI is better for detecting surface tumors at its early stage, while gamma scintig- raphy is a better choice for the detection of tumor in the body. Combined use of CLI and gamma scintigraphy might improve tumor detection.