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Preliminary Evaluation of 18F-Labeled Benzylguanidine Analogs as NET Tracers for Myocardial Infarction Diagnosis

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Abstract

Purpose

Heart failure (HF) remains a major cause of late morbidity and mortality after myocardial infarction (MI). To date, no clinically established 18F-labeled sympathetic nerve PET tracers for monitoring myocardial infarction are available. Therefore, in this study, we synthesized a series of 18F-labeled benzyl guanidine analogs and evaluated their efficacy as cardiac neuronal norepinephrine transporter (NET) tracers for myocardial imaging. We also investigated the preliminary diagnostic capabilities of these tracers in myocardial infarction animal models, as well as the structure-activity relationship of these tracers.

Procedures

Three benzyl guanidine-NET tracers, including [18F]1, [18F]2, and [18F]3, were synthesized and evaluated in vivo as PET tracers in a myocardial infarction mouse model. [18F]LMI1195 was used as a positive control for the tracers. H&E staining of the isolated myocardial infarction heart tissue sections was performed to verify the efficacy of the selected PET tracer.

Results

Our data show that [18F]3 had a moderate decay corrected labeling yield (~10%) and high radiochemical purity (>95%) compared to other tracers. The uptake of [18F]3 in normal mouse hearts was 1.7±0.1%ID/cc at 1 h post-injection (p. i.), while it was 2.4±0.1, 2.6±0.9, and 2.1±0.4%ID/cc in the MI mouse hearts at 1, 2, and 3 days after surgery, respectively. Compared with [18F]LMI1195, [18F]3 had a better myocardial imaging effect in terms of the contrast between normal and MI hearts. The area of myocardial infarction shown by PET imaging corresponded well with the infarcted tissue demonstrated by H&E staining.

Conclusions

With an obvious cardiac uptake contrast between normal mice and the myocardial infarction mouse model, [18F]3 appears to be a potential tool in the diagnosis of myocardial infarction. Therefore, it is necessary to conduct further structural modification studies on the chemical structure of [18F]3 to improve its in vivo stability and diagnostic detection ability to achieve reliable and practical imaging effects.

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Acknowledgements

The authors would like to thank Mr. Qiang Wan (Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University) for assistance with the cyclotron operation and the HRMS analysis of Jing Li (The Analytical Instrumentation Center of Sichuan University).

Funding

This work was funded by the National Natural Science Foundation of China (82001868), the Science and Technology Strategic Cooperation Programs of Luzhou Municipal People’s Government and Southwest Medical University (2021LZXNYD-J23). No other potential conflict of interest relevant to this article was reported.

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Author notes

  1. Liping Yang, Liping Yin, and Mei Hu contributed equally to this paper.

Authors and Affiliations

  1. Department of Nuclear Medicine, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou, Sichuan, China

    Liping Yang, Liping Yin, Mei Hu, Changjiang Wang, Yue Chen & Li Wang

  2. School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China

    Liping Yang, Liping Yin, Mei Hu & Changjiang Wang

  3. Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, China

    Liping Yang, Liping Yin, Mei Hu, Changjiang Wang, Yue Chen & Li Wang

  4. Department of Radiology, Lineberger Comprehensive Cancer Center, and Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA

    Weiling Zhao & Zibo Li

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  1. Liping Yang
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Contributions

LY and LY contributed to the labeling process, image scanning, data acquisition and analysis, and manuscript writing; CW participated in the precursor synthesis; MH contributed to the animal model preparation and staining experiment. WZ and ZL contributed to the data analysis and manuscript writing; WL and YC contributed to the study design, general control of the project, and manuscript writing and revision.

Corresponding authors

Correspondence to Yue Chen, Zibo Li or Li Wang.

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Yang, L., Yin, L., Hu, M. et al. Preliminary Evaluation of 18F-Labeled Benzylguanidine Analogs as NET Tracers for Myocardial Infarction Diagnosis. Mol Imaging Biol 25, 1125–1134 (2023). https://doi.org/10.1007/s11307-023-01844-3

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