131I-rhTSH在荷人分化型甲状腺癌裸鼠模型的体内分布和放射免疫显像

Biodistribution and radioimmunoimaging of 131I-rhTSH in human differentiated thyroid carcinoma-bearing nude mice model

摘要:

目的：以重组人促甲状腺素（recombinant human thyrotropin，rhTSH）为靶向探针，测定131I标记rhTSH的标记率、放化纯度和比活度，并探讨其在荷人分化型甲状腺癌（differentiated thyroid carcinoma，DTC）裸鼠模型中的体内分布情况和放射免疫显像（radioimmunoimaging，RII）。方法：采用氯胺T法，利用131I标记rhTSH，Sephadex G25M 柱纯化放射性标记物，纸层析法测定其标记率、放化纯度、室温稳定性及血清稳定性，并计算其放射性比活度，进而研究该放射性标记药物在荷K1裸鼠模型中的生物分布及RII情况。结果：131I-rhTSH标记率为（93.04±1.13）%，放化纯度为（97.71±1.14）%，比活度为（4.92±0.06）MBq/μg；131I-rhTSH放于室温1、6、12、24 h后所测得的放射性化学纯度分别为（92.94±0.34）%、（91.81±0.64）%、（91.38±1.20）%、（90.43±0.74）%；而与血清孵育1、6、12、24 h后所测得的放射性化学纯度分别为（92.59±0.73）%、（91.33±0.98）%、（91.01±0.73）%、（89.58±1.33）%。荷K1裸鼠模型的体内分布及单光子发射型计算机断层成像（single photon emission computed tomography，SPECT）显示分子探针131I-rhTSH可以在肿瘤组织中靶向聚集，在24 h 时肿瘤/肌肉（T/NT）比达最高，且肿瘤显影最清晰。结论：成功制备了分子探针131I-rhTSH，在荷人DTC裸鼠模型中有较好的靶向作用，为DTC的进一步诊治奠定基础。

Abstract:

Objective：To measure the labeling rate，radiochemical purity，and specific activity of 131I-labeled recombinant human thy－rotropin（rhTSH） as a targeting probe，and to investigate the distribution in vivo and radioimmunoimaging（RII） of 131I-rhTSH in a human differentiated thyroid carcinoma（DTC）-bearing nude mice model. Methods：rhTSH was labeled with 131I by the chloramine T method，and radioactively labeled rhTSH was purified using Sephadex G25M column. The labeling rate，radiochemical purity，room temperature stability，and serum stability were determined using paper chromatography，and the specific activity was calculated. Fur－thermore，the biodistribution and RII of the radioactively labeled drug in the K1 nude mice model were studied. Results：The labeling rate，radiochemical purity，and specific activity of 131I-rhTSH were（93.04±1.13）%，（97.71±1.14）%，and（4.92±0.06） MBq/μg，respectively. The radiochemical purity of 131I-rhTSH placed at room temperature for 1，6，12，and 24 hours was（92.94±0.34）%，（91.81±0.64）%，（91.38±1.20）%，and（90.43±0.74）%，respectively；after incubation with serum for 1，6，12，and 24 hours，the radiochemical purity was（92.59±0.73）%，（91.33±0.98）%，（91.01±0.73）%，and（89.58±1.33）%. Biodistribution and single photon emission computed tomography in the tumor-bearing K1 nude mice model showed that 131I-rhTSH was selectively concentrated in tumor tissues and the target/non-target ratio reached the highest at 24 hours with the clearest tumor imaging. Conclusion：The 131I-rhTSH molecular probe was successfully prepared，which has a good targeting effect in DTC-bearing nude mice model，laying a foundation for further diagnosis and treatment of DTC.