<sup>89</sup>Zr-PET Radiochemistry in the Development and Application of Therapeutic Monoclonal Antibodies and Other Biologicals

Positron emission tomography with 89Zr can be used to follow the behaviour of therapeutic monoclonal antibodies (mAbs) and other biologicals in vivo. The favourable radiophysical characteristics of 89Zr allow multiple days PET scanning after injection. For the coupling of 89Zr to proteins six desferrioxamine (DFO)-based bifunctional chelators have been described, five of which forming stable complexes in vivo. Of the methods that give stable complexes three are based on random lysine modification of mAbs and two on site-specific engineering. Up to now only two methods, random lysine modification with N-suc-DFO or DFO-Bz-NCS, have been used in clinical studies. In this review firstly aspects of the physicochemical properties and production of 89Zr are emphasized as well as important items that have to be taken into account for current good manufacturing practice (cGMP) compliant production of 89Zr-labeled proteins. Next, the different DFO-based conjugation strategies will be discussed with respect to synthesis, and their (pre)clinical evaluation particularly in the field of oncology. Keywords: Biologicals, immuno-PET, monoclonal antibodies, PET, positron emission tomography, proteins, radiometal, zirconium-89