Radioiodinated recombinant human TSH: A novel radiopharmaceutical for thyroid cancer metastases detection

The follow-up of differentiated thyroid cancer (DTC) is currently performed by serum Tg levels determination and whole body scan (WBS) with I-131. 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. Aim: In this study we describe an alternative tracer, radiolabeled rhTSH, for the diagnosis of non-iodine uptaking DTC metastases. Methods: rhTSH was iodinated with I-125 or I-123 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 mug of I-123-rhTSH (100 muCi) and static images were acquired at 30 minutes, 1, 2, and 3 hours. Animals were then sacrificed and dissected for organ counting. Results: RhTSH was radioiodinated to high specific activity: 132.2 mCi/mg for I-123-rhTSH, 94.3 for I-125-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. Conclusion: Results obtained so far suggest that radiolabeled rhTSH might be a promising radiopharmaceutical for diagnosis and follow-up of DTC.