分化型甲状腺癌(DTC)细胞可能会失去NIS表达和碘摄取,但通常表达TSH受体(TSHR)。因此,我们的研究目的是比较两种放射性标记的超激动剂TSH类似物的DTC成像效果.这些类似物(即TR1401和TR1402)具有比重组人TSH(Thyrogen®)更高的TSHR结合亲和力。使用间接方法通过HYNIC缀合用the-99m进行放射性标记,然后进行体外质量控制和对TSHR阳性细胞系(ML-1)的结合测定。还进行了体外结合测定,并与放射性标记的人重组TSH进行比较。用99mTc-TR1401SPECT/CT对四只患有实质性低分化区域的自发性滤泡性甲状腺癌的狗进行了体内成像,99mTc-TR1402SPECT/CT,在2周内的不同天和[18F]FDGPET/CT。TR1401和TR1402具有高的比活性(8.3±1.2MBq/µg),并保留了其生物活性和结构完整性。与99mTc-Thyrogen(Kd=8.4nM)相比,两种激动剂均能够有效结合由细胞系表达的TSHR受体,对于99mTc-TR1401,解离常数(Kd)为2.7nM,对于99mTc-TR1402,解离常数(Kd)为0.5nM。在肿瘤靶向实验中,在患有自发性腺内甲状腺癌的狗中观察到局灶性摄取,其中通过免疫组织化学证实了TSHR的表达。99mTc-TR1402提供的T/B高于99mTc-TR1401和[18F]FDG(分别为12.9±1.3、10.2±0.7和3.8±0.6;所有p<0.001)。鉴于这些结果,99mTc-TR1402似乎是甲状腺癌体内成像的有用工具。
Differentiated thyroid cancer (DTC) cells may lose NIS expression and iodine uptake, but usually express TSH receptors (TSHR). Therefore, the aim of our study was to compare two radiolabeled superagonist TSH analogues for DTC imaging. These analogues (namely TR1401 and
TR1402) have a higher TSHR binding affinity than recombinant human TSH (Thyrogen®). Radiolabeling was performed with technetium-99m using an indirect method via HYNIC conjugation and was followed by in vitro quality controls and binding assay on TSHR-positive cell lines (ML-1). An in vitro binding assay was also performed and compared with radiolabeled human recombinant TSH. In vivo imaging was performed in four dogs with spontaneous follicular thyroid carcinoma with solid poorly differentiated areas with 99mTc-TR1401 SPECT/CT, 99mTc-
TR1402 SPECT/CT, and [18F]FDG PET/CT on different days within 2 weeks. TR1401 and
TR1402 were labeled with high specific activity (8.3 ± 1.2 MBq/µg) and retention of their biological activity and structural integrity. Both agonists were able to efficiently bind TSHR receptors expressed by cell lines with dissociation constants (Kd) of 2.7 nM for 99mTc-TR1401 and 0.5 nM for 99mTc-TR1402 compared with 99mTc-Thyrogen (Kd = 8.4 nM). In tumor-targeting experiments, a focal uptake was observed in dogs with spontaneous intraglandular thyroid carcinoma, in which TSHR expression was confirmed by immunohistochemistry. 99mTc-
TR1402 provided higher T/B than 99mTc-TR1401 and [18F]FDG (12.9 ± 1.3, 10.2 ± 0.7, and 3.8 ± 0.6, respectively; all p < 0.001). Given these results, 99mTc-
TR1402 appears to be a useful tool for in vivo imaging of thyroid cancer.