Radiochemistry with {Al18F}2+: Current status and optimization perspectives for efficient radiofluorination by complexation

With the aim to efficiently develop and synthesize new radiotracers for PET imaging, and their use for theranostic approaches, radiolabeling technics have not ceased to progress. Among the major advances, complexation of {Al18F}2+, developed for the first time in 2009, has enriched and simplified the radiofluorination techniques. Indeed, advantages of the fluorine-18 (T = 109.7 min, pure β+ emitter and low β+ energy max = 634 keV) to obtain images with good quality compared to other β+ emitter and advantages of chelation chemistry (fast reaction and simple purification by SPE) were combined. Today, applications are numerous with radiotracers developed and used in clinical trials for the diagnosis of lung cancer, glioblastoma, breast cancer, prostate cancer, or neuroendocrine tumors. However, despite the high potential of theses radiotracers, no consensus seems to be emerging on the conditions of radiolabeling, which may be a hindrance to the rapid development of future radiotracers. This review aimed to analyze all the radiolabeling conditions with all chelators used since 2009 in order to determine, firstly, which conditions are the more efficient are and, secondly whether a universal method can be used with this technique. The aim is to answer the following questions: (1) which type of chelator to use? (2) How should the fluoride-18 solution be prepared? (3) Is it beneficial to have a two-step procedure compared to a one-step procedure? (4) what are the optimal amounts of reagents? (5) What are the optimal conditions (pH, temperature, reaction time) for the radiolabeling? (6) How can the resulting radiotracer be purified? Moreover, this review focused on the limitations of this strategy, in particular regarding automation.