A new study has found that a targeted alpha therapy may benefit patients with thyroid cancer that does not respond to standard radioactive iodine treatment. Researchers have tested the use of 211At (astatine), an alpha-emitting radionuclide, in patients whose differentiated thyroid cancer (DTC) had become refractory to traditional beta-emitting radioactive iodine.
Standard care for recurrent or metastatic DTC after total thyroidectomy involves repeated doses of radioactive iodine. Some patients, however, see their disease progress despite this approach and are classified as refractory. At that point, they are typically treated with molecular-targeted agents such as kinase inhibitors.
The research team led by Watabe developed a therapy using 211At-NaAt and conducted a phase I clinical trial to evaluate its safety and efficacy. The trial used three escalating doses—1.25, 2.5, and 3.5 MBq/kg—administered intravenously to assess adverse events, pharmacokinetics, absorbed dose, and therapeutic effect. Response was measured through thyroglobulin levels, CT imaging, and 131I SPECT imaging.
Results indicated that the targeted alpha-therapy could be safely administered at all doses tested, though some dose-limiting toxicities were observed at the highest level of 3.5 MBq/kg but remained within tolerable limits. Early signs of effectiveness were seen in patients receiving either 2.5 or 3.5 MBq/kg; these included more than a 50 percent reduction in thyroglobulin and decreased uptake in lesions visible on imaging.
"Our findings provide the first evidence that 211At based therapy is both feasible and therapeutically promising in patients who no longer respond to conventional radioactive iodine," stated Watabe. "Because 211At (astatine) therapy may achieve disease control without requiring molecular targeted drugs, it has the potential to reduce treatment burden, limit adverse effects associated with systemic therapies, and broaden access to effective care for patients with refractory disease."
"In addition," he noted, "211At can be produced using accelerator cyclotrons, and its availability will expand globally as more production facilities come online. The successful clinical application of 211At in this study marks an important milestone for the field, opening the door to widespread adoption of cyclotron-based alpha-therapy and accelerating future innovations in molecular imaging and targeted radionuclide therapy."
The study's findings were published in the December issue of The Journal of Nuclear Medicine.
