Gallium-68 and zirconium-89 complexes of DFO-analogs for molecular imaging applications using PET/CT

Background The β + -emitters gallium-68 ( 68 Ga) and zirconium-89 ( 89 Zr) are among the most widely used metallic radionuclides in nuclear medicine for diagnostic imaging by Positron Emission Tomography (PET). Inspired by nature’s bacterial siderophore desferrioxamine-B (DFO), a number of structurally related oligohydroxamate-based chelators have been studied for the complexation of both radiometals and for applications in nuclear medicine. We report here the solid phase (sp) synthesis of a new member of this family of acyclic chelators, DFO* sp 3, and its comparison with DFO 1 (control) and DFO-analogs DFO* 2, and oxoDFO* 4 in vitro and in vivo. Results DFO* sp 3 and oxoDFO* 4 were synthesized efficiently on solid support by applying different protective group strategies. The [ 68 Ga]Ga- and [ 89 Zr]Zr-labeled chelators 1–4 were obtained with high radiochemical yield and purity. They were also found to be of favorable hydrophilicity (logP <-2,2), high stability in the media tested, and low protein binding (with the exception of [ 68 Ga]Ga-DFO 5 and [ 68 Ga]Ga-DFO* 6). In vivo, the radiometal complexes 5–12 showed good serum stability, fast clearance predominantly by renal excretion and low uptake in organs and tissues. In vivo PET/CT imaging confirmed the results of the ex vivo biodistribution studies, leading to the acquisition of high-quality PET/CT images with a low signal-to-noise ratio. Conclusion The excellent in vitro and in vivo characteristics of [ 68 Ga]Ga- and [ 89 Zr]Zr-complexes of hydroxamate-based chelators 1–4 support their use in radiopharmaceutical development and diagnostic PET-imaging applications in nuclear medicine.