Corsetti Frederica, Chianelli Marco, Cornelissen Bart, Van de Wiele Christophe, D'Alessandria Calogero, Slegers Guido, Mather Stephen J, Di Mario Umberto, Filetti Sebastiano, Scopinaro Francesco, Signore Alberto
University "La Sapienza," Rome, Rome, Italy.
Cancer Biother Radiopharm. 2004 Feb;19(1):57-63. doi: 10.1089/108497804773391685.
The follow-up of differentiated thyroid cancer (DTC) is currently performed by serum Tg levels determination and whole body scan (WBS) with 131I. In this regard, the latter represents the main tool to localize metastatic tissue, but is characterized by the induction of severe hypothyroidism. Moreover, WBS displays poor sensitivity in poorly differentiated tumors due to a loss of iodine uptake capacity.
In this study we describe an alternative tracer, radiolabeled rhTSH, for the diagnosis of non-iodine uptaking DTC metastases.
rhTSH was iodinated with 125I or 123I using an enzymatic method with lactoperoxidase/glucose oxidase. In vitro stability of labeled compounds was assessed in saline and serum and in vivo studies were performed in tumor-bearing nude mice. Three mice were inoculated with ARO cells (TSH receptor negative) and three with PTC-1 cells (TSH receptor positive). After 25 days, mice were injected with 10 microg of 123I-rhTSH (100 microCi) and static images were acquired at 30 minutes, 1, 2, and 3 hours. Animals were then sacrificed and dissected for organ counting.
RhTSH was radioiodinated to high specific activity: 132.2 mCi/mg for 123I-rhTSH, 94.3 for 125I-rhTSH. In vitro stability tests revealed no significant release of radioiodine. A clear tumor uptake was detectable after 2 hours in all animals implanted with PTC-1.
Results obtained so far suggest that radiolabeled rhTSH might be a promising radiopharmaceutical for diagnosis and follow-up of DTC.
目前，分化型甲状腺癌（DTC）的随访是通过测定血清Tg水平和进行131I全身扫描（WBS）来进行的。在这方面，后者是定位转移组织的主要工具，但其特点是会导致严重的甲状腺功能减退。此外，由于碘摄取能力丧失，WBS在低分化肿瘤中的敏感性较差。
在本研究中，我们描述了一种用于诊断不摄取碘的DTC转移灶的替代示踪剂——放射性标记的重组人促甲状腺素（rhTSH）。
使用乳过氧化物酶/葡萄糖氧化酶的酶促方法，用125I或123I对rhTSH进行碘化。在生理盐水和血清中评估标记化合物的体外稳定性，并在荷瘤裸鼠中进行体内研究。给三只小鼠接种ARO细胞（促甲状腺素受体阴性），三只接种PTC - 1细胞（促甲状腺素受体阳性）。25天后，给小鼠注射10μg的123I - rhTSH（100μCi），并在30分钟、1小时、2小时和3小时采集静态图像。然后处死动物并解剖进行器官计数。
rhTSH被放射性碘化至高比活度：123I - rhTSH为132.2mCi/mg，125I - rhTSH为94.3mCi/mg。体外稳定性测试显示没有明显的放射性碘释放。在所有植入PTC - 1的动物中，2小时后可检测到明显的肿瘤摄取。
目前获得的结果表明，放射性标记的rhTSH可能是一种用于DTC诊断和随访的有前景的放射性药物。
