Development and clinical application of targeted alpha therapy using astatine (²¹¹At)

Targeted alpha therapy (TAT) is gaining attention for its superior therapeutic efficacy compared to conventional radionuclide therapy using beta-emitters. Recently, astatine (²¹¹At) has been garnering attention as an alpha-emitting radionuclide, as it can be produced by irradiating natural bismuth targets with alpha beams using a 30-MeV cyclotron. We are conducting an investigator-initiated clinical trial using [²¹¹At] NaAt as an iodine analogue for patients with refractory thyroid cancer. Compared to beta-emitters such as ¹³¹I or ¹⁷⁷Lu, the administration dose is small for alpha-emitters. Furthermore, ²¹¹At emits lower-energy gamma rays than beta-emitters, resulting in reduced radiation exposure to the surrounding individuals. We have already conducted investigations and demonstrated that radiation exposure remains far below the limits for the general public and caregivers, even if the patient leaves the radiation-controlled area immediately after the administration of [²¹¹At] NaAt (Watabe T, et al. Ann Nucl Med. 2021). Therefore, hospitalisation in an isolation ward within the RI-controlled area is not required for targeted alpha therapy using [²¹¹At] NaAt. Moreover, the imaging capability of ²¹¹At enables precise estimation of the absorbed doses in organs at risk. With the potential for labelling to peptides and antibodies, ²¹¹At is anticipated to be a versatile therapeutic agent for various cancers.