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Apoptosis imaging studies in various animal models using radio-iodinated peptide

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Abstract

Apoptosis has a role in many medical disorders and treatments; hence, its non-invasive evaluation is one of the most riveting research topics. Currently annexin V is used as gold standard for imaging apoptosis. However, several drawbacks, including high background, slow body clearance, make it a suboptimum marker for apoptosis imaging. In this study, we radiolabeled the recently identified histone H1 targeting peptide (ApoPep-1) and evaluated its potential as a new apoptosis imaging agent in various animal models. ApoPep-1 (CQRPPR) was synthesized, and an extra tyrosine residue was added to its N-terminal end for radiolabeling. This peptide was radiolabeled with 124I and 131I and was tested for its serum stability. Surgery- and drug-induced apoptotic rat models were prepared for apoptosis evaluation, and PET imaging was performed. Doxorubicin was used for xenograft tumor treatment in mice, and the induced apoptosis was studied. Tumor metabolism and proliferation were assessed by [18F]FDG and [18F]FLT PET imaging and compared with ApoPep-1 after doxorubicin treatment. The peptide was radiolabeled at high purity, and it showed reasonably good stability in serum. Cell death was easily imaged by radiolabeled ApoPep-1 in an ischemia surgery model. And, liver apoptosis was more clearly identified by ApoPep-1 rather than [124I]annexin V in cycloheximide-treated models. Three doxorubicin doses inhibited tumor growth, which was evaluated by 30–40 % decreases of [18F]FDG and [18F]FLT PET uptake in the tumor area. However, ApoPep-1 demonstrated more than 200 % increase in tumor uptake after chemotherapy, while annexin V did not show any meaningful uptake in the tumor compared with the background. Biodistribution data were also in good agreement with the microPET imaging results. All of the experimental data clearly demonstrated high potential of the radiolabeled ApoPep-1 for in vivo apoptosis imaging.

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Acknowledgments

This work was supported by R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (Nos. 2013R1A2A2A01012250, 2013M2A2A6042317, 2012-0006386, 20090078235) and the Basic Research Laboratory (BRL) Program (2013R1A4A1069507). The Korea Basic Science Institute (Daegu) is acknowledged for the NMR and MS measurements.

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Authors and Affiliations

  1. Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea

    Wonjung Kwak, Yeong Su Ha, Nisarg Soni, Woonghee Lee, Se-Il Park, Heesu Ahn & Jeongsoo Yoo

  2. Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea

    Gwang Il An

  3. Department of Biochemistry and Cell Biology and Cell & Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea

    In-San Kim & Byung-Heon Lee

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  1. Wonjung Kwak
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  2. Yeong Su Ha
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Correspondence to Gwang Il An or Jeongsoo Yoo.

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Wonjung Kwak, Yeong Su Ha and Nisarg Soni have contributed equally to this work.

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Kwak, W., Ha, Y.S., Soni, N. et al. Apoptosis imaging studies in various animal models using radio-iodinated peptide. Apoptosis 20, 110–121 (2015). https://doi.org/10.1007/s10495-014-1059-z

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