Gallium-68: a systematic review of its nononcological applications

The increased availability of PET facilities worldwide has sparked renewed interest in the use of generator-produced tracers such as gallium-68 (Ga). Imaging with Ga provides exciting opportunities in terms of new ligand-labelling possibilities and the exploration of novel clinical applications. The aim of the study was to summarize and appraise what has been published on the clinical applications of Ga outside oncology practice. This systematic review was based on the PRISMA guidelines. Databases searched include PubMed, Medline, Scopus, Web of Science and Google Scholar. The following search strategy was used: 'Ga' OR 'Gallium' (all fields) NOT the following (title and abstract): Oncology/NET/neuroendocrine tumour/tumor/DOTATOC, DOTATATE, DOTANOC. These results were further limited to English publications, which resulted in 205 publications on PubMed. After duplicates and irrelevant articles were removed, 72 publications remained for inclusion. Only those studies in which compounds were labelled with Ga for applications other than in oncology-related indications were included. Publications in which the focus was on oncology-related applications of Ga imaging or in which the emphasis was on aspects relating to generators, radiochemistry or physics were excluded. Although a multitude of tracers have been labelled with Ga over several decades, it has not been established in routine clinical practice yet. In addition, neuroendocrine and other oncological applications have dominated the field until relatively recently following reports of applications in infection and inflammation. The majority of publications to date involve small numbers of subjects in mainly preclinical settings. Differences in methodology preclude grouping of studies to reach a clear conclusion. There is wide scope for Ga tracer application outside oncological practice, which remains greatly underutilized. Larger clinical trials are needed to validate these applications.