Radionuclidic Impurity Pathways in Cyclotron Production: Insights from 18F and Emerging Theranostic Radionuclides

(1) Cyclotron production of medical radionuclides can generate unintended radionuclidic impurities, influencing product quality, radiation safety, and radioactive waste management. This review aims to establish a general mechanistic framework for the formation, transfer, and control of such impurities. (2) We identified published data on theranostic radionuclides, liquid- and solid-target production, 18F-associated impurities, and activation products through a Scopus search and reference screening. A total of 147 publications were qualitatively synthesized. (3) Production of 18F from H218O served as a reference model for tracing impurity pathways from irradiation through transfer, purification, radiosynthesis, and waste management. Three principal sources can be distinguished: competing nuclear reactions involving the target isotope and residual isotopes; reactions involving other target-matrix constituents; and activation of target windows, bodies, and auxiliary materials. Impurity fate depends on release from the formation site, transfer into the processing stream, and retention or removal during purification and radiosynthesis. (4) The 18F model demonstrates that all of these stages should be considered when designing and validating new cyclotron-production routes. Co-produced isotopes of the product element require predominantly upstream control, whereas chemically distinct radionuclides can often be separated but are redistributed within the manufacturing system.