Automated zirconium-89 and lutetium-177 antibody labeling and formulation using a Trasis MiniAIO module

Radiolabeled antibodies are used to select the right treatment for the right patient by determining antigen expression levels in vivo. In addition, antibodies labeled with therapeutic nuclides can be used for cancer treatment. To efficiently produce these labeled antibodies in constant high quality, automated procedures are desired. This research describes the labeling and formulation of zirconium-89 and lutetium-177 labeled Dinutuximab on the Trasis MiniAIO module, as proof-of-principle antibody to be used for GD2 imaging and therapy in neuroblastoma patients.

Dinutuximab was modified for labeling with a DFO- or DOTA-chelator using isothiocyanate chemistry. Radiolabeling with zirconium-89 and lutetium-177 and subsequent purification and formulation were performed using the Trasis MiniAIO and compared to manual synthesis procedures. Radiochemical purity was assessed by iTLC and HPLC. Immunoreactivity was evaluated using a radioligand binding assay on antigen coated wells.

Radiolabeled products were obtained with good radiochemical yield of 76 ± 8 % for [⁸⁹Zr]Dinutuximab 70 ± 8 % for [¹⁷⁷Lu]Dinutuximab. Immunoreactivity was >50 % for zirconium-89 and lutetium-177 labeled constructs, which was similar to immunoreactivity of products obtained by manual synthesis. Manually obtained radiochemical yields were somewhat higher as a result of residual radioactivity in valves and tubings in automated synthesis runs, however losses were minimized through incorporation of several washing steps. Generally, yields were comparable with previously reported automation procedures and importantly, satisfactory for human application.

We have developed a reproducible and high-yielding automated method for the synthesis and formulation of radiolabeled diagnostic and therapeutic antibodies on a Trasis MiniAIO module. This method should assist in obtaining labeled products with consistent quality while simultaneously reducing the workers radiation dose.