Abstract
Nuclear and optical dual-modality probes can be of great assistance in prostate cancer localization, providing the means for both preoperative nuclear imaging and intraoperative surgical guidance. We developed a series of probes based on the backbone of the established GRPR-targeting radiotracer NeoB. The inverse electron demand of the Diels–Alder reaction was used to integrate the sulfo-cyanine 5 dye. Indium-111 radiolabeling, stability studies and a competition binding assay were carried out. Pilot biodistribution and imaging studies were performed in PC-3 tumor-bearing mice, using the best two dual-labeled probes. The dual-modality probes were radiolabeled with a high yield (>92%), were proven to be hydrophilic and demonstrated high stability in mouse serum (>94% intact labeled ligand at 4 h). The binding affinity for the GRPR was in the nanomolar range (21.9–118.7 nM). SPECT/CT images at 2 h p.i. clearly visualized the tumor xenograft and biodistribution studies, after scanning confirmed the high tumor uptake (8.47 ± 0.46%ID/g and 6.90 ± 0.81%ID/g for probe [111In]In-12 and [111In]In-15, respectively). Receptor specificity was illustrated with blocking studies, and co-localization of the radioactive and fluorescent signal was verified by ex vivo fluorescent imaging. Although optimal tumor-to-blood and tumor-to-kidney ratios might not yet have been reached due to the prolonged blood circulation, our probes are promising candidates for the preoperative and intraoperative visualization of GRPR-positive prostate cancer.
Highlights
We aim to demonstrate the potential of the novel gastrin-releasing peptide receptor (GRPR)-targeting dual-modality probes for preoperative and intraoperative prostate cancer (PCa) visualization
Extensive research has been carried out on probes targeting the prostate-specific membrane antigen (PSMA), but it has been suggested that GRPR-targeted imaging probes may be of great value for PSMA-negative tumor lesions [23]
The overexpression of GRPR typically occurs at an early stage of the disease, while PSMA is often associated with late-stage disease
Summary
Prostate cancer (PCa) is the second most frequently diagnosed cancer among men, with about 1.4 million new cases in 2020 alone [1]. The surgical removal of the prostate gland, in whole or in part, combined with pelvic lymph node dissection is one of the most widely used treatment options to cure localized PCa [2]. Successful in many cases, the recurrence rate after radical prostatectomy is still as high as 20–40% [3]. One of the indicators for an increased risk of relapse is the observation of positive surgical margins [4]. As well as the multifocal nature of many primary prostate tumors, the need to maintain physiological functions, such as potency and continence, constitutes an additional
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