Prostate cancer (PCa), the most widespread male cancer in western countries, is generally eradicated by surgery, especially if localized. However, during surgical procedures, it is not always possible to identify malignant tissues by visual inspection. Among the possible consequences, there is the formation of positive surgical margins, often associated with recurrence. In this work, the gastrin-releasing peptide receptor (GRPR), overexpressed in the prostatic carcinoma and not in healthy tissues or in benign hyperplasia (BPH), is proposed as target molecule to design a novel near-infrared fluorescent (NIRF) probe for image-guided prostatectomy.
The NIRF dye Sulfo-Cy5.5 was conjugated to a Bombesin-like peptide (BBN), targeting GRPR. The final product, called BBN-Cy5.5, was characterized and tested in vitro on PC-3, DU145, and LnCAP cell lines, using unconjugated Sulfo-Cy5.5 as control. In vivo biodistribution studies were performed by optical imaging in PC-3 tumor-bearing and healthy mice. Finally, simulation of the surgical protocol was carried out.
BBN-Cy5.5 showed high water solubility and a good relative quantum yield. The ability of the probe to recognize the GRPR, highly expressed in PC-3 cells, was tested both in vitro and in vivo, where a significant tumor accumulation was achieved 24 h post-injection. Furthermore, a distinguishable fluorescent signal was visible in mice bearing PCa, when the surgery was simulated. By contrast, low signal was found in healthy or BPH-affected mice.
This work proposes a new NIRF probe ideal to target GRPR, biomarker of PCa. The promising data obtained suggest that the dye could allow the real-time intraoperative visualization of prostate cancer.
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Fondazione Umberto Veronesi is gratefully acknowledged for the support.
Dr. Marina Boido is gratefully acknowledged for the help in acquisition of confocal images.
The project was carried out thanks to the financial support of AIRC Investigator Grant IG 2013.
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The authors declare that they have no conflicts of interest.
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Pagoto, A., Garello, F., Marini, G.M. et al. Novel Gastrin-Releasing Peptide Receptor Targeted Near-Infrared Fluorescence Dye for Image-Guided Surgery of Prostate Cancer. Mol Imaging Biol 22, 85–93 (2020). https://doi.org/10.1007/s11307-019-01354-1
- Image-guided surgery
- Prostate cancer
- Gastrin-releasing peptide receptor (GRPR)
- Near-infrared probe
- Orthotopic mouse model