Dong-Yeon Kim1, Ayoung Pyo2, Misun Yun3, Ramar Thangam2, Sung-Hwan You2, Ying Zhang2, Ye-Rim Jung4, Dinh-Huy Nguyen2, Akhil Venu2, Hyeon Sik Kim5, Mee Sun Yoon6, Yeongjin Hong4,7, Jung-Joon Min4,7. 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.
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.
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.
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