cGMP production of radiometal solutions from solid targets at a university-scale facility

Radiometals have emerged as a critical tool for positron emission tomography. These radionuclides provide the opportunity for theranostic pairs, using the same compound with different radionuclides complexed at the same position. Additionally, radiometals span a range of half-lives, from minutes to days, providing excellent flexibility in matching radioactive half-lives with the biological half-lives of targeting vectors. However, cyclotron production of these radiometals is not yet standardized. Some radiometals have common purification and production methods, but there is still a need for widespread, easily adoptable current Good Manufacturing Practices (cGMP) methods. Such methods would minimize the use of custom, in-house methods and rely on widely available instrumentation. In this work, [⁸⁹Zr]ZrCl₄ was produced under cGMP methods to provide a framework for simple, rapid production and purification with commonly available instrumentation. [⁸⁹Zr]ZrCl₄ was produced at 40.02 MBq/μA-h and underwent standard quality control analyses to determine appearance, pH (1-2), radioactive concentration (185-1850 MBq/mL), specific activity (>370 MBq/μg), radionuclidic and radiochemical purity (both >99%), chemical purity (from oxalate, <1% and metallic impurities, <75 μg/mL total), endotoxins (<17 EU/mL), and sterility (no growth). All specifications for release of a cGMP batch of [⁸⁹Zr]ZrCl₄ across the validation runs were passed. This work highlights the need for standardized methods for production, purification, and quality control for radiometal solutions and provides an example of such methods for [⁸⁹Zr]ZrCl₄.