Recent synthetic strategies for the direct C–H activation radiofluorination and radioiodination of aromatic systems

Radiopharmaceuticals are crucial for diagnostic imaging and targeted therapies due to their specificity and high therapeutic effectiveness, have attracted much attention in the field of biomedical sciences. Radiopharmaceuticals consist of radionuclides and drugs, and the radionuclides can be classified as metalic and nonmetalic radionuclides. Among nonmetallic radioisotopes, radiofluorine and radioiodines are the most commonly used halogen sources. Radiolabeling as an approach introducing radionuclides to the pharmaceutical active reagents have been well developed in recent years. Among these radionuclide labeling methods, C–H direct radiofluorination and radioiodination of alkyl- and arene- containing molecules have been developed in fast, simple and convenient transformation, which starting from readily available precursors, and have provided new potential in radiopharmaceutical synthesis. In this review, we have summarized the advanced strategies and the applications of direct C–H radiofluorination and radioiodination methodologies over the past few years. Overall, these methods have broadened the development space with the integration of new technologies.