Favorable performance of DGPR1008, a novel PSMA-targeted near-infrared fluorescent probe, for image-guided prostate cancer surgery in experimental models

Background Near-infrared (NIR) fluorescence-guided surgery has shown promise for prostate cancer (PCa). Despite several prostate-specific membrane antigen (PSMA)-targeted NIR probes entering clinical trials, none have received approval to date, highlighting the continuing need for novel agents with improved pharmacokinetic and imaging properties to support NIR fluorescence-guided surgery. DGPR1008, a newly designed PSMA-targeted NIR probe, has been proposed as a potential candidate probe. Consequently, this study primarily aimed to characterize the binding specificity of DGPR1008 to PSMA and evaluate its imaging and pharmacological profiles. A secondary aim was to compare its performance with that of the already clinically evaluated probe OTL78 in animal models. Methods The PSMA-binding specificity of DGPR1008 was assessed in vitro in three PCa cell lines. Also, in vivo tumor targeting and fluorescence imaging, along with assessment of the biodistribution, pharmacokinetics, excretory clearance, and toxicity of DGPR1008, were performed in animal models. Finally, the pharmacokinetics, tissue distribution, imaging contrast, and tumor-to-background ratios of DGPR1008 were compared with those of the reference probe OTL78 at various time points post-injection. Results Binding assays performed in the three PCa cell lines demonstrated the high affinity of DGPR1008 for PSMA. Meanwhile, the in vivo tests showed that DGPR1008 achieved selective tumor accumulation and rapid non-target clearance. Compared to the reference probe OTL78, DGPR1008 exhibited stronger, more persistent tumor fluorescence and tumor-to-background contrast in mice bearing subcutaneous xenografts. Furthermore, DGPR1008 displayed favorable pharmacokinetics and excretion profiles, with a notably faster plasma clearance than the reference probe OTL78. Conclusion DGPR1008 demonstrated high PSMA specificity in vitro and favorable imaging performance in a PCa xenograft mouse model. Together with its favorable pharmacokinetic and safety profiles, these findings support the use of DGPR1008 as a promising real-time NIR fluorescence imaging probe for guiding PCa surgery with potential for clinical translation.