Fusarinine C,a novel siderophore‐based bifunctional chelator for radiolabeling with Gallium‐68

Fusarinine C (FSC), a siderophore‐based chelator coupled with the model peptide c(RGDfK) (FSC(succ‐RGD)₃), revealed excellent targeting properties in vivo using positron emission tomography (PET). Here, we report the details of radiolabeling conditions and specific activity as well as selectivity for ⁶⁸Ga. ⁶⁸Ga labeling of FSC(succ‐RGD)₃ was optimized regarding peptide concentration, pH, temperature, reaction time, and buffer system. Specific activity (SA) of [⁶⁸Ga]FSC(succ‐RGD)₃ was compared with ⁶⁸Ga‐1,4,7‐triazacyclononane, 1‐glutaric acid‐4,7 acetic acid RGD ([⁶⁸Ga]NODAGA‐RGD). Stability was evaluated in 1000‐fold ethylenediaminetetraacetic acid (EDTA) solution (pH 7) and phosphate‐buffered saline (PBS). Metal competition tests (Fe, Cu, Zn, Al, and Ni) were carried out using [⁶⁸Ga]‐triacetylfusarinine C. High radiochemical yield was achieved within 5 min at room temperature, in particular allowing labeling with ⁶⁸Ga up to pH 8 with excellent stability in 1000‐fold EDTA solution and PBS. The 10‐fold to 20‐fold lower concentrations of FSC(succ‐RGD)₃ led to the same radiochemical yield compared with [⁶⁸Ga]NODAGA‐RGD with SA up to 1.8 TBq/µmol. Metal competition tests showed high selective binding of ⁶⁸Ga to FSC. FSC is a multivalent siderophore‐based bifunctional chelator allowing fast and highly selective labeling with ⁶⁸Ga in a wide pH range and results in stable complexes with high SA. Thus it is exceptionally well suited for the development of new ⁶⁸Ga‐tracers for in vivo molecular imaging with PET.