Summary Radiofluorination is one of the most important processes in molecular imaging, and to date, metal- centered fluorination by either substitution or exchange mechanisms have been infrequently designed and implemented for short-lived fluorine-18 since its inception in the early 1970s. The broad aims of the project are to develop new methods of fluorine-18 incorporation into complex molecules by using irreversible metal-fluorine bond formation. This will both complement and contrast the currently existing fluorination methods for radiochemistry, including that of aluminium fluoride (AlF), which has proven successful but with some apparent limitations. Each metal center will be evaluated for its pharmacological properties, as well as indirect effects such as the capacity to act as a multi-modality core or ability to pair with a therapeutic isotope in the same chelator to create a theranostic pair, and upon testing the suitable functionality that the methods are resistant to, we will demonstrate the best routes (as defined by the properties measured previously) in a head-to-head against currently existing AlF radiolabeling for a well-known biological target, prostate-specific membrane antigen (PSMA) and carbonic anhydrase IX (CAIX), that we have extensive experience in handling and imaging in-house. At the same time, application of successful methods within the GMP set-up will enable swift future translation and progress of a method, rather than being abandoned as unsuitable for human-use.

Project Narrative The goal of this project is to develop a series of new metal-based radiolabeled fluorination reactions that will expand the currently available spectrum of methods to incorporate fluorine-18 for structurally diverse molecules in PET imaging. Fluorine-19 chemistry has progressed substantially with varied and elegant methodologies, but the isotopic short-lived isotope fluorine-18 radiochemistry has lagged behind. This work will add towards the end-goal of personalized medicine, as we strive to be able to create and image highly functionalized biomolecules, use multimodality imaging and develop new “theranostic pairs” for targeted therapy, improving patient care.