[Clinical Application of Targeted Alpha Therapy Using Astatine].

Targeted alpha therapy is gaining prominence owing to its superior therapeutic efficacy compared with conventional radionuclide therapies using beta emitters. Astatine (At, half-life: 7.2 h) has recently emerged as a promising alpha emitter, along with actinium (Ac) and lead (Pb). It can be produced domestically by irradiating natural bismuth targets with alpha particles using a 30 MeV cyclotron. Chemically analogous to iodine, astatine accumulates in differentiated thyroid cancer cells via the sodium/iodide symporter and demonstrated significant antitumor effects in a xenograft model. At The University of Osaka, we completed the first-in-human investigator-initiated clinical trial using [At]sodium astatide (NaAt) in patients with metastatic thyroid cancer refractory to radioiodine (I) therapy. The disappearance of iodine-avid lesions and a marked reduction in serum thyroglobulin levels (a tumor marker) were observed, suggesting clinical efficacy. In addition, we developed At-labeled compounds targeting the prostate-specific membrane antigen (PSMA), and a clinical trial is currently underway to confirm their efficacy and safety in preclinical studies. Furthermore, pan-tumor-targeting probes, including amino acid derivatives specific for L-type amino acid transporter 1 (LAT1) and antibodies targeting ephrin type-A receptor 2 (EphA2), are under active development and optimization for clinical applications. Targeted alpha therapy using astatine has great potential to significantly alter the future landscape of cancer therapy.