Abstract 2671: Multimodality imaging of ovarian cancer using HER2 affibody conjugated nanoparticles.

Objectives: Specific and sensitive detection of ovarian cancer using non-invasive or intraoperative imaging approaches holds great promise for improving survival of the cancer patients through early diagnosis of ovarian cancer and image-guided surgery. In this study, we have developed Near infrared (NIR) dye labeled HER2 targeted magnetic iron oxide nanoparticles (IONPs) that enable detecting orthotopic ovarian cancers in nude mice using five imaging approaches, including 2D optical imaging, 3D-fluorescence tomography, MRI, spectroscopic imaging, and photoacoustic imaging.Methods: HER2 affibodies (ZHER2:342) were labeled with a NIR-dye 830 and then conjugated to a 10 nm core size IONP coated with amphiphilic polymer. Sensitivity of different imaging approaches in cancer detection was determined by direct injection of 5 x 103 to 3 x 106 of the nanoparticle probe-labeled tumor cells into the ovary of the mice and then imaged using 2D Kodak in vivo optical imaging system, MRI, and three new intraoperative hand-held imaging devices, including Spectroscopic, 3D-fluorescent tomography and photoacoustic imaging. Specificity of targeted tumor imaging was demonstrated by system delivery of the NIR830-ZHER2:342-IONP imaging probes in orthotopic human ovarian cancer xenograft models in nude mice. Histological examination of tumor and normal tissues further confirmed tumor targeting specificity.Results: HER2 affibody conjugated IONPs are excellent imaging probes for 2D-NIR optical, 3D-fluorescence tomography, spectroscopic device, photoacoustic and MR imaging of HER2 positive ovarian cancer lesions. Both 2D-optical imaging and MRI were able to detect ovarian tumors as small as 2 mm in size non-invasively. Photoacoustic imaging showed 5-times higher NIR signal in the tumor bearing mice injected with HER2 targeted IONPs than that of non-targeted IONP injected mice. However our handheld spectroscopic device result illustrated a high sensitivity in detection of small metastatic tumor lesions in the peritoneal cavity intra-operatively . Prussian blue staining revealed the presence of HER2 targeted IONPs in the tumor lesion as well as distant metastases lesions. Similarly all the above imaging systems were sensitive to detect at least 104 tumor cells labeled with HER2 affibody conjugated IONPs and implanted into the ovary for 24h. The ability of multi-modality tumor imaging following systemic delivery of single targeted nanoparticle platform make it possible for taking advantages of different imaging methods to increase sensitivity and specificity of tumor targeting and imaging. Conclusion: Based on the above results, the NIR dye-labeled and HER2 targeted IONPs developed by our group have great potential for development of multimodality imaging approaches that can be applied to ovarian cancer detection, image-guided and targeted therapy, and image-guided surgery. Citation Format: Minati Satpathy, Weiping Qian, Rafal Zielinski, Liya Wang, Lei Xi, Jacek Capala, Andrew Wang, Malgorzata Lipowska, Brad A. Kairdolf, Huabei Jiang, Shuming Nie, Hui Mao, Lily Yang. Multimodality imaging of ovarian cancer using HER2 affibody conjugated nanoparticles. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2671. doi:10.1158/1538-7445.AM2013-2671