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Article Open Access

Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion

  • Authors:
    • Xietian Pan
    • Qing Xu
    • Jiangwei Chen
    • Tingting Wang
    • Mingming Zhang
    • Haichang Wang
    • Haokao Gao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China, Department of Radiation Oncology, The Affiliated Bayi Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210002, P.R. China, Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
    Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2276-2284
    |
    Published online on: June 27, 2019
       https://doi.org/10.3892/mmr.2019.10432
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Abstract

Glucagon‑like peptide‑1 (GLP‑1) and its receptor (GLP‑1R) exert cardioprotective effects after myocardial ischemia and reperfusion (MI/R) in animal models and human clinical trials. Receptor imaging with positron emission tomography (PET) provides a non‑invasive method for monitoring GLP‑1R expression. In the present study, a fluorine‑18‑labeled aluminum fluoride exendin‑4 analog [18F‑AlF conjugated with 1,4,7‑triazacyclononanetriacetic acid (NOTA)‑maleimide (MAL)‑Cys40‑exendin‑4] was synthesized and evaluated in a rat MI/R model for GLP‑1R imaging. NOTA‑MAL‑Cys40‑exendin‑4 was synthesized by coupling Cys40‑exendin‑4 with NOTA‑MAL. NOTA‑MAL‑Cys40‑exendin‑4 was then conjugated with 18F‑AlF to obtain 18F‑AlF‑NOTA‑MAL‑Cys40‑exendin‑4. The yield of 18F‑AlF‑NOTA‑MAL‑Cys40‑exendin‑4 was 18.5±3.4% (not decay corrected). The process was completed within ~30 min. In rat MI/R models, the tracer exhibited specific binding to GLP‑1R and an appropriate signal‑to‑noise ratio. At 8 h post‑MI/R, tracer uptake reached its peak [0.35±0.053% of injected dose (%ID)/g; n=6] in ischemic myocardium. Localized tracer uptake decreased 1 day (0.20±0.032 %ID/g; n=6) and 3 days (0.16±0.017 %ID/g; n=6) post‑MI/R compared with 8 h post‑MI/R, but still remained higher compared with sham‑operated groups (0.06±0.012 %ID/g; n=6). Pre‑injected unlabeled exendin‑4 effectively blocked tracer accumulation (0.09±0.041 %ID/g; n=6). In conclusion, 18F‑AlF‑NOTA‑MAL‑Cys40‑exendin‑4 demonstrated favorable characteristics for GLP‑1R imaging following MI/R. PET imaging using 18F‑AlF‑NOTA‑MAL‑Cys40‑exendin‑4 in rodent hearts after MI/R revealed a dynamic pattern of GLP‑1R upregulation.
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Copy and paste a formatted citation
Spandidos Publications style
Pan X, Xu Q, Chen J, Wang T, Zhang M, Wang H and Gao H: Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion. Mol Med Rep 20: 2276-2284, 2019.
APA
Pan, X., Xu, Q., Chen, J., Wang, T., Zhang, M., Wang, H., & Gao, H. (2019). Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion. Molecular Medicine Reports, 20, 2276-2284. https://doi.org/10.3892/mmr.2019.10432
MLA
Pan, X., Xu, Q., Chen, J., Wang, T., Zhang, M., Wang, H., Gao, H."Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion". Molecular Medicine Reports 20.3 (2019): 2276-2284.
Chicago
Pan, X., Xu, Q., Chen, J., Wang, T., Zhang, M., Wang, H., Gao, H."Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion". Molecular Medicine Reports 20, no. 3 (2019): 2276-2284. https://doi.org/10.3892/mmr.2019.10432
Copy and paste a formatted citation
x
Spandidos Publications style
Pan X, Xu Q, Chen J, Wang T, Zhang M, Wang H and Gao H: Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion. Mol Med Rep 20: 2276-2284, 2019.
APA
Pan, X., Xu, Q., Chen, J., Wang, T., Zhang, M., Wang, H., & Gao, H. (2019). Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion. Molecular Medicine Reports, 20, 2276-2284. https://doi.org/10.3892/mmr.2019.10432
MLA
Pan, X., Xu, Q., Chen, J., Wang, T., Zhang, M., Wang, H., Gao, H."Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion". Molecular Medicine Reports 20.3 (2019): 2276-2284.
Chicago
Pan, X., Xu, Q., Chen, J., Wang, T., Zhang, M., Wang, H., Gao, H."Preliminary evaluation of 18F‑AlF‑NOTA‑MAL‑Cys40‑Exendin‑4 in rodent heart after myocardial ischemia and reperfusion". Molecular Medicine Reports 20, no. 3 (2019): 2276-2284. https://doi.org/10.3892/mmr.2019.10432
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