The ⁶⁸Ga-siderophore approach to infection imaging:evaluation of [68Ga]Ga-DFO in patients with vascular graft infection

Purpose: Gallium-68 complexes with siderophores, typically isostructural with their iron(III) analogues and recognized by microbial Fe(III)-siderophore complex receptors, are candidates for PET imaging of microbial infection. Here we evaluate [68Ga]Ga-desferrioxamine-B complex ([68Ga]Ga-DFO) for imaging in patients with infected aortic grafts.<br/>Methods: The trial was registered on clinical trials.gov, NCT05285072 registered 16 March 2022. [68Ga]Ga-DFO was produced from 68Ga-generator eluate in acetate buffer and characterized by radioHPLC, iTLC and LCMS. Its stability in human serum was evaluated in vitro by protein precipitation and size exclusion chromatography, and its biodistribution, pharmacokinetics and dosimetry determined by PET imaging in healthy mice. PET imaging in two patients with aortic graft infections was performed over 90 minutes, with blood and urine sampling in one patient.<br/>Results: Analysis of [68Ga]Ga-DFO identified it as a 1:1 complex of 68Ga with DFO, with &gt;95% radiochemical purity, stable in human serum in the absence of bicarbonate at high DFO:protein ratio, but not in the presence of bicarbonate with low DFO:protein ratio. It was rapidly cleared renally from healthy mice but in humans, clearance was much slower consistent with significant protein binding. There was no specific uptake at infection sites identified by [18F]FDG scanning.<br/>Conclusion: We conclude that future clinical evaluation of the [68Ga]Ga-siderophore approach to infection imaging requires a deeper understanding of the kinetics and thermodynamics of transchelation of 68Ga between the siderophores and transferrin.<br/>