A new solid target design for the production of 89 Zr and radiosynthesis of high molar activity [ 89 Zr]Zr-DBN.

Due to the advent of various biologics like antibodies, proteins, cells, viruses, and extracellular vesicles as biomarkers for disease diagnosis, progression, and as therapeutics, there exists a need to have a simple and ready to use radiolabeling synthon to enable noninvasive imaging trafficking studies. Previously, we reported [Zr]zirconium--isothiocyanatobenzyl-desferrioxamine ([Zr]Zr-DBN) as a synthon for the radiolabeling of biologics to allow PET imaging of cell trafficking. In this study, we focused on improving the molar activity (A) of [Zr]Zr-DBN, by enhancing Zr production on a low-energy cyclotron and developing a new reverse phase HPLC method to purify [Zr]Zr-DBN. To enhance Zr production, a new solid target was designed, and production yield was optimized by varying, thickness of yttrium foil, beam current, irradiation duration and proton beam energy. After optimization, 4.78±0.33 GBq (129.3±8.9 mCi) of Zr was produced at 40 µA for 180 min (3 h) proton irradiation decay corrected to the end of bombardment with a saturation yield of 4.56±0.31 MBq/µA. Additionally, after reverse phase HPLC purification the molar activity of [Zr]Zr-DBN was found to be in 165-316 GBq/µmol range. The high molar activity of [Zr]Zr-DBN also allowed radiolabeling of low concentration of proteins in relatively higher yield. The stability of [Zr]Zr-DBN was measured over time with and without the presence of ascorbic acid. The newly designed solid target assembly and HPLC method of [Zr]Zr-DBN purification can be adopted in the routine production of Zr and [Zr]Zr-DBN, respectively.