Radiolabeling and in vitro studies of scandium-44 with HOPO chelator for PET imaging

44Sc has been attracting interest as a clinically viable PET (positron emission tomography) imaging radionuclide due to its high positron branching ratio, 3.97 hour half-life, ideal positron energy of 632 keV and ability to be produced from a generator as well as from a cyclotron. Scandium is also of interest since the coordination is similar to the lanthanides and Ga3+ that have demonstrated labeling methods. Further, 47Sc (a potential therapeutic radionuclide) can serve as a matched isotope pair for theranostic applications. While the labeling studies of 44Sc with DOTA and DOTA derivatives are quite extensive, there is little data on complexation of scandium with the chelator 3,4,3-(LI-1,2-HOPO). This ligand has been used successfully to radiolabel 89Zr where it was shown to have high stability in vivo. Additionally, preliminary studies with 86Y, and non-radioactive scandium show promising complexation constants similar to those found with DOTA derivatives. One major advantage of using HOPO is that radiolabeling can be achieved at room temperature while DOTA requires elevated temperatures, that may be detrimental when radiolabeling biomolecules. Radiolabeling of generator produced 44Sc versus cyclotron produced 44Sc is also under investigation as there are currently several different post-elution purification methods of generator 44Sc, and the potential radiolabeling complications of these eluents has not yet been studied. This work focuses on radiolabeling HOPO with generator produced 44Sc and the in vitro and radioanalytical evaluation of the resulting complexes.