Global Landscape of Radiopharmaceutical Innovation: Emerging Targets and Molecules

ABSTRACT Following the recent commercial success of FDA‑approved targeted radiopharmaceuticals, an increasing number of pipeline candidates have advanced into clinical trials. Analyzing their development timelines, study durations, and clinical outcomes enables researchers to discern current trends and identify agents with promising commercial potential. This review provides a global overview of radiopharmaceutical development, with a focus on disease targets, radionuclides, ligand platforms, and clinical indications. Our analysis reveals that, alongside established targets such as PSMA and SSTR, emerging targets—including CAIX, GPC3, and DLL3—are broadening the spectrum of cancers amenable to radiopharmaceutical intervention. Concurrently, the adoption of therapeutic radionuclides with potent antitumor efficacy, particularly 225 Ac, 212 Pb, and 161 Tb, is gaining momentum. Examination of unsuccessful cases highlights persistent challenges, notably radionuclide supply constraints and in vivo toxicity. Encouragingly, regulatory frameworks are becoming more flexible to expedite development, and first‑in‑human studies offer an early opportunity to eliminate poor‑performing candidates before large‑scale trials. Nevertheless, there remains an urgent need for standardized clinical trial protocols to bridge the gap between clinical investigation and regulatory evaluation. Overall, this review aims to bridge the informational and technological gaps among laboratory–based basic research, hospital–based clinical trials, and industrial development, thereby offering insights for future progress and assisting in overcoming the obstacles facing radiopharmaceutical discovery.