Direct Radiofluorination Of A Heat-Sensitive Antibody By Al-F-18 Complexation

F-18 is the most widely used radionuclide for PET imaging. However, peptides and antibodies cannot be radiolabeled with fluorine-18 without the extra attachment of an auxiliary group, and these biomolecules are typically radiolabeled indirectly through two reaction steps. The Al-F-18 complex has recently been developed as a new radiolabeling technique; however, the harsh conditions required for Al-F-18 complexation have restricted its widespread application for heat-sensitive biomolecules. Here we report fully optimized Al-F-18 radiofluorination enabling successful radiolabeling under mild conditions. Six different macrocyclic chelators with different backbones (NOTA, DOTA, and NODA) and pendant arms were tested for efficient radiolabeling using the Al-F-18 complex. We also optimized the radiolabeling conditions to achieve radiofluorination at a lower temperature by changing the radioactive fluorine source, labeling buffer, and organic solvent. By employing a NODA backbone chelator bearing two acetate pendant arms and one benzyl-NCS moiety, >60% Al-F-18 complexation was achieved at 30 degrees C in ammonium acetate buffer (pH 5.5). An antibody conjugated with the NODA chelator was also successfully radiolabeled with F-18 at 30 degrees C using Al-F-18 complexation without loss of immunoreactivity.