²¹¹At targeted alpha therapy in Europe: overcoming clinical, regulatory, and infrastructure challenges.

Abstract

Targeted Alpha Therapy (TAT) holds considerable promise for precision oncology, yet its clinical deployment in Europe remains limited. Beyond scientific considerations, progress is constrained by fragmentation across the radiopharmaceutical value chain, encompassing radionuclide production, radiochemistry, preclinical validation, clinical development, regulatory frameworks, infrastructure, and workforce training. This editorial focuses on astatine‑211 (²¹¹At) as a strategically important radionuclide for European targeted alpha therapy. Its favorable decay characteristics, chemical versatility, and theranostic potential make ²¹¹At a strong candidate for clinical translation. However, despite advances in radiochemistry and encouraging early‑phase clinical experience, current evidence remains largely preclinical or restricted to first‑in‑human studies, and broader clinical adoption remains uncertain. We argue that the main barriers are not isolated technical obstacles but a self‑reinforcing dynamic linking limited supply, restricted clinical evidence generation, regulatory complexity, and insufficient workforce readiness. Addressing these challenges sequentially or in isolation is unlikely to succeed. Instead, coordinated, value‑chain‑driven approaches are required, in which production, preclinical research, clinical evaluation, regulation, and training progress together. From a European perspective, initiatives such as ACCELERATE.EU: an EU-HORIZON-JU-IHI funded project bringing together a consortium of 17 partners across Europe with expertise in ²¹¹At and targeted alpha therapies, illustrate how distributed production networks, harmonized practices, co‑clinical development, and structured workforce training can contribute to greater autonomy, resilience, and equitable patient access. Establishing a decentralized and sustainable European supply model for ²¹¹At should therefore be considered a strategic priority to enable multicenter clinical trials, supply independence and support the future integration of targeted alpha therapy into routine clinical practice.