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

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 [Ga]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 [Ga]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 [Ga]Ga-NYM016 uptake at 2.5 min after injection. At 3 h after injection, [Ga]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, [Ga]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 [Ga]Ga-NYM016 uptake was observed at the prostate site of a patient with prostatitis.

Conclusion: The novel fluorescence probe NYM016 and the radioactive tracer [Ga]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.