Abstract 2070: In vivo imaging of therapy response to novel antibody mixtures targeted at the human epidermal growth factor receptor family using FDG and FLT positron emission tomography

Dysregulation and overexpression of the human epidermal growth factor receptor (HER) family plays an important role in many cancers. Simultaneously targeting multiple members of the HER family may increase the therapeutic efficacy. Here, we report the ability to image the therapeutic response obtained by targeting the HER family members individually or simultaneously using novel monoclonal antibody (mAb) mixtures. Mice with subcutaneous BxPC-3 pancreas adenocarcinomas were divided into five groups (n=8) receiving vehicle or mAb mixtures directed against HER1 (EGFR), HER2, HER3, or pan-HER. Small animal positron emission tomography/computed tomography (PET/CT) with 18 F-FDG and 18 F-FLT was performed at baseline and day 1 or 2 after initiation of therapy. The changes in tumor uptake of tracers were quantified and related to the efficacy of each therapy on tumor size measured by caliper. Imaging results were further validated by immunohistochemistry on tumor samples obtained 2 and 7 days after initiation of therapy. The pan-HER mAb mixture showed the greatest efficacy with significant smaller tumor volumes (146±39 mm 3 , Mean ±SEM) compared with the other groups (vehicle: 660±99 mm 3 , EGFR: 363±67 mm 3 , HER2: 458±45 mm 3 , HER3: 274±37 mm 3 ) at the end of therapy (day 23). Mean FDG and FLT uptake in the pan-HER group decreased by 19±4.3% and 24±3.1%, respectively, at day 1 or 2 compared with baseline, which was significantly greater than for the other groups. Importantly, the early change in mean FDG and FLT uptake correlated with tumor growth at day 23 relative to day 0 (r=0.67, p In conclusion, we demonstrate the ability to image therapeutic responses to a novel pan-HER mAb mixture using PET/CT imaging with FDG and FLT. We suggest the use of FDG and FLT PET/CT as an imaging biomarker in clinical evaluation of the pan-HER mAb mixture. Citation Format: Carsten H. Nielsen, Mette M. Jensen, Helle J. Jacobsen, Thomas T. Poulsen, Ivan D. Horak, Johan Lantto, Michael Kragh, Andreas Kjaer. In vivo imaging of therapy response to novel antibody mixtures targeted at the human epidermal growth factor receptor family using FDG and FLT positron emission tomography. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2070. doi:10.1158/1538-7445.AM2014-2070