ImmunoPET and biodistribution with human epidermal growth factor receptor 3 targeting antibody Zr-89-RG7116

The humanized monoclonal antibody with high affinity for the human epidermal growth factor receptor (HER) 3, RG7116, is a glycoengineered, IgG1 class antibody. By labeling RG7116 with zirconium-89 (Zr-89) we aimed to visualize in vivo HER 3 expression and study the biodistribution of this antibody in human tumor-bearing mice. Biodistribution of 89Zr-RG7116 was studied in subcutaneously xenografted FaDu tumor cells (HER 3-positive). Dose-dependency of Zr-89-RG7116 organ distribution and specific tumor uptake was assessed by administering doses ranging from 0.05 to 10 mg/kg RG7116 to SCID/Beige mice. Biodistribution was analyzed at 24 and 144 h after injection. MicroPET imaging was performed at 1, 3, and 6 days after injection of 1.0 mg/kg Zr-89-RG7116 in the FaDu, H441, QG-56 and Calu-1 xenografts with varying HER 3 expression. The excised tumors were analyzed for HER 3 expression. Biodistribution analyses showed a dose-and time-dependent Zr-89-RG7116 tumor uptake in FaDu tumors. The highest tumor uptake of Zr-89-RG7116 was observed in the 0.05 mg/kg dose group with 27.5% ID/g at 144 h after tracer injection. MicroPET imaging revealed specific tumor uptake of Zr-89-RG7116 in FaDu and H441 models with an increase in tumor uptake over time. Biodistribution data was consistent with the microPET findings in FaDu, H441, QG56 and Calu-1 xenografts, which correlated with HER 3 expression levels. In conclusion, Zr-89-RG7116 specifically accumulates in HER 3 expressing tumors. PET imaging with this tracer provides realtime non-invasive information about RG7116 distribution, tumor targeting and tumor HER 3 expression levels.