Abstract

Abstract Early decision on tumor response after anti-cancer treatment is still an unmet medical need. Here we exploited ApoPep-1 peptide that binds to histone H1 exposed on apoptotic cell surface as a probe and investigated whether in vivo imaging of apoptosis using near-infrared fluorescence dye-labeled linear and cyclic (disulfide-bonded) form of ApoPep-1 at an early stage after treatment could enable us predict tumor response to the treatment later. Treatment of SNU16 stomach tumor cells with cistplatin and cetuximab alone significantly induced apoptosis of the cells, while combination of cisplatin and cetuximab more efficiently induced apoptosis, as detected by staining with linear and cyclic form of ApoPep1. However, the differences among groups were more remarkable when detected with cyclic form of ApoPep-1 compared to the linear counterpart. In tumor-bearing mice, apoptosis imaging was performed at the first and second week after the initiation of treatment, and tumor sizes and weights were measured 3 weeks after treatment. In vivo fluorescence imaging signals by the homing of ApoPep-1 to tumor was most remarkable in the group injected with cyclic form of ApoPep-1 at the first week after combined treatment with cisplatin plus cetuximab. There were no significant differences in tumor sizes and weights between groups injected with linear and cyclic form of ApoPep-1. Correlation analysis revealed that imaging signals 1 week after treatment with cisplatin and cetuximab in combination were most closely related with tumor volume changes (r2 = 0.934). These results demonstrate that in vivo apoptosis imaging using the cyclic form of Apopep-1 is a sensitive and predictive tool for early decision on stomach tumor response after anti-cancer treatment. Citation Format: Fatima Khan, Smriti Gurung, Hyun-Kyung Jung, Moon-Chang Baek, Yong Woo Choi, In San Kim, Byung Heon Lee. Peptide probe-based in vivo imaging of apoptosis and early decision on stomach tumor response to treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2918. doi:10.1158/1538-7445.AM2015-2918

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