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Abstract
Surface-exposed calreticulin (ecto-CRT) is a well-known "eat-me" signal exhibited by dying cells that contributes to their recognition and destruction by the immune system. We assessed the use of a CRT-specific binding peptide for imaging ecto-CRT during immunogenic cell death and its utility for early prediction of treatment response. Methods: A synthetic CRT-specific peptide, KLGFFKR (CRTpep), was labeled with fluorescein isothiocyanate or 18F, and the characteristics of ecto-CRT were evaluated in a colon cancer cell line in vitro and in vivo. Results: In vitro flow cytometry, immunofluorescence staining, and in vivo small-animal PET imaging results showed that CRTpep detected preapoptotic cells treated with immunogenic drugs or radiation but not those treated with the nonimmunogenic drug or a nontherapeutic dose of immunogenic drug. Conclusion: The present results indicate that the CRT-specific peptide would enable the prediction of therapeutic response, thereby facilitating early decisions on continuation or discontinuation of immunogenic treatment.

Affiliations

Dong-Yeon Kim  1 , Ayoung Pyo  2 , Misun Yun  3 , Ramar Thangam  2 , Sung-Hwan You  2 , Ying Zhang  2 , Ye-Rim Jung  4 , Dinh-Huy Nguyen  2 , Akhil Venu  2 , Hyeon Sik Kim  5 , Mee Sun Yoon  6 , Yeongjin Hong  4   7 , Jung-Joon Min  4   7
1 College of Pharmacy and Research Institute of Pharmaceutical Science, Gyeongsang National University, Jinju, Korea.
2 Institute for Molecular Imaging and Theranostics, Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea.
3 Microbiology and Functionality Research Group, Research and Development Division, World Institute of Kimchi, Gwangju, Korea.
4 Institute for Molecular Imaging and Theranostics, Department of Nuclear Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea; jjmin@jnu.ac.kr yjhong@chonnam.ac.kr.
5 Medical Photonics Research Center, Korea Photonics Technology Institute, Gwangju, Korea.
6 Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea; and.
7 Department of Microbiology, Chonnam National University Medical School, Hwasun, Korea.