Development of ABT-806i, a Kit-formulated 111In-ABT-806 antibody directed to EGFR for tumor imaging

396 Objectives ABT-806 is a humanized antibody targeting a unique epitope on EGFR only available for binding when EGFR is overexpressed, activated, or when the EGFRvIII mutation is present. This property allows for a higher tumor to normal tissue contrast and thus enables ABT-806 for payload delivery. We have therefore developed 111In-labeled ABT-806 (ABT-806i) for SPECT imaging of EGFR positive tumors. Methods The ABT-806 antibody was conjugated with either DTPA or CHX-A’-DTPA and used to generate 111In-labeled ABT-806 (ABT-806i) which was characterized to evaluate its radiochemical features and its relative tumor-specific binding properties using nanoSPECT/CT image quantification. Results Selective tumor targeting of 111In-labeled ABT-806 (ABT-806i) was demonstrated in both wild-type EGFR overexpressing tumor xenografts (11 ± 2.1 %ID/cc) and EGFRvIII positive tumor xenografts, 21.5 ± 4.3%ID/cc in flank and 75.1 ± 11.3 %ID/cc as orthotopic glioma. The specific tumor uptake was inhibited gradually by co-dosing increasing concentrations of unlabeled ABT-806 antibody, from which a tumor occupancy curve was generated to estimate the dose for 50% tumor saturation as 13 mg/kg in flank xenografts. ABT-806 conjugated to CHX-A’-DTPA was GMP manufactured as a formulated kit. The labeling efficiency with sterile 111In was consistently higher than 95% for the instant preparation. The immunoreactive fraction was 0.8 ± 0.06 and the product is stable for 5 days and the prepared ABT-806i retained the favorable in vivo biodistribution and tumor targeting features. Conclusions These features render ABT-806i a promising imaging agent currently under clinical validation for characterization of tumor EGFR status. Research Support Abbott Labs