Abstract 5233: Imaging breast cancer xenograft using multienergy modality and target-specific molecular agents

Abstract Interleukin-11 (IL-11) and its receptor (IL-11R) involve in many normal and abnormal biological progress. Studies strongly suggest that interleukin-11 (IL-11) plays an important role in early bone metastases. We synthesized an IL-11Rα homing peptide identified from in vivo patient screening with a peptide phage display and to conjugate it to both an NIR dye for optical imaging and a chelator for nuclear imaging. Cell binding and internalization of the imaging agent was evaluated using NIR confocal microscopy and human breast cancer MDA-MB-231 cell lines. Specificity was demonstrated by comparing with free dye and blocking with the unlabeled recombinant IL-11. Tumor cell growth, vasculature formation and IL-11 agent binding to the tumor were demonstrated in vivo using luciferase positive tumor xenograft model and the injection of both vasculature and IL-11 agents. Tissue autoradiography and H&E staining of the same tissue sections were conducted to verify imaging data. Biodistribution was analyzed by percentage injection dose per gram tissue. Confocal microscopy demonstrated that the target specific imaging agent accumulated on the cell membrane and internalized into cell while free dye had significant lower cell binding than the IL-11 agent. Pre-incubated by the presence of IL-11 protein significantly decreased the agent binding to the cell. Multienergy in vivo imaging revealed the tumor growth, vasculature formation and IL-11 agent binding on the tumor as early as 4 days after the tumor cell inoculation. Overlaid the autoradiography tissue image with H&E staining results demonstrated the heterogeneous distribution of the imaging agent inside tumor mass. Furthermore, the images showed the IL-11 agent only bound to the viable tumor cells. These results suggest a potential imaging agent for study IL-11Rα expression at noninvasive whole body level as well as organ, tissue and cellular levels. *WW, XQ: These authors contributed equally to this work. Grant support: DoD W81XWH-08-1-0489, Department of Defense, Department of Radiology research fund, Curtis Hankamer Basic Research Fund and the L.E. and Josephine S. Gordy Memorial Cancer Research Fund, Dan L. Duncan Cancer Center Scholar, American Society for Clinical Oncology and Hope Street Kids Foundation, and National Science Foundation of China grants (30471988, 30973409, and 30873027). Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5233.