The article discusses the practical considerations and (pre-)clinical perspectives of implementing Ac-225 labeled radiopharmaceuticals for targeted alpha therapy (TAT). Ac-225, with its high linear energy transfer (LET) and short tissue penetration, offers advantages over beta-emitters in treating metastatic cancers. The production and availability of Ac-225 are expected to increase, making it more accessible for clinical use. However, the high toxicity of Ac-225 presents significant challenges in handling and quality control (QC) due to health physics regulations. Key aspects of working with Ac-225 include: 1. **Radionuclide Production**: Ac-225 is currently produced from Th-229, with alternative production methods like spallation and proton irradiation under investigation. 2. **Radiochemistry**: Challenges in labeling conditions, chelator selection, and biological vector choice are discussed, emphasizing the importance of purity and stability. 3. **Quality Control (QC)**: Ac-225's detection is complex due to its alpha emission, requiring equilibrium with daughter nuclides like Fr-221 and Bi-213. Various QC techniques, including radio-TLC, HPLC, and HP-Ge detectors, are used, with specific considerations for low activity levels. 4. **Preclinical and Clinical Use**: Preclinical studies often involve small amounts of Ac-225, while clinical applications require lower activities. Radiation protection and health physics are crucial, especially given the high toxicity of Ac-225. The article highlights the need for infrastructure and methods to ensure the safe and effective use of Ac-225 labeled radiopharmaceuticals, emphasizing the importance of proper labeling conditions, QC processes, and patient administration protocols.The article discusses the practical considerations and (pre-)clinical perspectives of implementing Ac-225 labeled radiopharmaceuticals for targeted alpha therapy (TAT). Ac-225, with its high linear energy transfer (LET) and short tissue penetration, offers advantages over beta-emitters in treating metastatic cancers. The production and availability of Ac-225 are expected to increase, making it more accessible for clinical use. However, the high toxicity of Ac-225 presents significant challenges in handling and quality control (QC) due to health physics regulations. Key aspects of working with Ac-225 include: 1. **Radionuclide Production**: Ac-225 is currently produced from Th-229, with alternative production methods like spallation and proton irradiation under investigation. 2. **Radiochemistry**: Challenges in labeling conditions, chelator selection, and biological vector choice are discussed, emphasizing the importance of purity and stability. 3. **Quality Control (QC)**: Ac-225's detection is complex due to its alpha emission, requiring equilibrium with daughter nuclides like Fr-221 and Bi-213. Various QC techniques, including radio-TLC, HPLC, and HP-Ge detectors, are used, with specific considerations for low activity levels. 4. **Preclinical and Clinical Use**: Preclinical studies often involve small amounts of Ac-225, while clinical applications require lower activities. Radiation protection and health physics are crucial, especially given the high toxicity of Ac-225. The article highlights the need for infrastructure and methods to ensure the safe and effective use of Ac-225 labeled radiopharmaceuticals, emphasizing the importance of proper labeling conditions, QC processes, and patient administration protocols.