Radiolabelling of the octadentate chelators DFO* and oxoDFO* with zirconium-89 and gallium-68.

In recent years, clinical imaging with zirconium-89 (Zr)-labelled monoclonal antibodies (Ab) by positron emission tomography (immunoPET) has been gaining significant importance in nuclear medicine for the diagnosis of different types of cancer. For complexation of the radiometal Zr and its attachment to the Ab, chelating agents are required. To date, only the hexadentate chelator desferrioxamine (DFO) is applied in the clinic for this purpose. However, there is increasing preclinical evidence that the [Zr]Zr-DFO complex is not sufficiently stable and partly releases the radiometal in vivo due to the incomplete coordination sphere of the metal. This leads to unfavourable unspecific uptake of the osteophilic radiometal in bones, hence decreasing the signal-to-noise-ratio and leading to an increased dose to the patient. In the past, several new chelators with denticities > 6 have been published, notably the octadentate DFO derivative DFO*. DFO*, however, shows limited water solubility, wherefore an oxygen containing analogue, termed oxoDFO*, was developed in 2017. However, no data on the suitability of oxoDFO* for radiolabelling with Zr has yet been reported. In this proof-of-concept study, we present the first radiolabelling results of the octadentate, water-soluble chelator oxoDFO*, as well as the in vitro stability of the resulting complex [Zr]Zr-oxoDFO* in comparison to the analogous octadentate, but less water-soluble derivative DFO* and the current "standard" chelator DFO. In addition, the suitability of DFO* and oxoDFO* for radiolabeling with the short-lived PET metal gallium-68 is discussed. The water-soluble, octadentate chelator oxoDFO* provides stable complexes with the positron emitter Zirconium-89. The radiolabelling can be performed at room temperature and neutral pH and thus, oxoDFO* represents a promising chelator for applications in immunoPET.