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A novel PSMA targeted dual-function near-infrared fluorescence and PET probe for the image-guided surgery and detection of prostate cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Prostate-specific membrane antigen (PSMA) is a promising diagnostic biomarker for prostate cancer (PCa). NYM016, a novel small-molecule PSMA-targeted fluorescence probe for the surgical navigation of PCa, was designed in this work. Furthermore, the potential of the PET agent [68Ga]Ga–NYM016 for the radionuclide imaging of PCa was evaluated.

Methods

NYM016 was designed with the near-infrared fluorescent group Cyanine 7 (Cy7) and the chelating group NOTA. The radioactive probe [68Ga]Ga–NYM016 was designed and synthesized on the basis of NYM016. The abovementioned probes were assessed in PSMA-positive xenograft-bearing models and patients diagnosed with PCa.

Results

NYM016 obviously aggregated in the tumor site of the mouse model, and its fluorescence intensity was stable within 24 h. NYM016 was well-tolerated, and no adverse events were found in the clinical study. Moreover, it was also observed in the excised lesions from the patient with PCa, and its fluorescence aggregated at the same site where PSMA was highly expressed. In addition, the PSMA xenograft demonstrated intense [68Ga]Ga–NYM016 uptake at 2.5 min after injection. At 3 h after injection, [68Ga]Ga–NYM016 uptake by the PSMA xenograft gradually increased to 6.40 ± 0.19%ID/g, which was higher that by the blocked and negative groups (2.28 ± 0.07%ID/g, P < 0.05; 2.28 ± 0.22%ID/g, P < 0.05). In the clinical study, [68Ga]Ga–NYM016 was well-tolerated and no adverse events were observed. Substantial accumulation was observed in primary and metastatic lesions in a patient with recurrence with the maximum standardized uptake value of 18.93. Meanwhile, negative [68Ga]Ga–NYM016 uptake was observed at the prostate site of a patient with prostatitis.

Conclusion

The novel fluorescence probe NYM016 and the radioactive tracer [68Ga]Ga–NYM016 are promising candidates for the surgical navigation and radionuclide imaging of PCa, respectively.

Trial registration

The clinical evaluation of this study was registered at Clinicaltrial.gov (NCT05623878) on 21 Dec, 2022.

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Data Availability

The original data are available upon request.

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Acknowledgements

The authors want to thank all the clinical and research staff at the Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University for their technical assistance and helpful discussions.

Funding

Funding This work was supported by the Subject Construction Fund from Wuxi Medicine School of Jiangnan University, the Subject Development Fund (FZXK2021011) from Wuxi Health Select Committee, and the Clinical Research and Translational Medicine Research Fund (LCYJ202301) from Affiliated Hospital of Jiangnan University.

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Author notes

  1. Haitian Fu and Kequan Lou contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214000, China

    Haitian Fu, Kequan Lou, Huihui He, Yanjuan Wang, Liping Chen, Yu Zhang & Chunjing Yu

  2. Department of Urological Surgery, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214000, China

    Yuanyuan Mi

  3. Wuxi School of Medicine, Jiangnan University, No. 1800, Lihu Avenue, Wuxi, 214000, China

    Wenjin Li & Chunjing Yu

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  1. Haitian Fu
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Contributions

The Project design: Haitian Fu and Chunjing Yu. Experiment construction and implementation: Haitian Fu, Kequan Lou, Huihui He, Wenjin Li, Liping Chen, Yu Zhang, and Yuanyuan Mi. Data acquisition and processing: Haitian Fu, Kequan Lou, Huihui He, Wenjin Li, and Yanjuan Wang. Writing of manuscripts: Haitian Fu and Kequan Lou. Supervision and coordination of the project: Chunjing Yu. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chunjing Yu.

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No potential conflicts of interest relevant to this article exist.

Ethics approval

The study was granted by the Ethics Committee of Jiangnan University. The study involving human participants was in line with the principles of the ethics committee of Affiliated Hospital of Jiangnan University and the Declaration of Helsinki in 1964.

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Fu, H., Lou, K., He, H. et al. A novel PSMA targeted dual-function near-infrared fluorescence and PET probe for the image-guided surgery and detection of prostate cancer. Eur J Nucl Med Mol Imaging (2023). https://doi.org/10.1007/s00259-023-06492-x

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