PSMA-targeted fluorescent probe for NIR-II imaging in prostate cancer intraoperative navigation and tumor margin mapping.
[UNLABELLED] Accurate delineation of tumor margins during prostate cancer surgery remains challenging due to limited intraoperative visualization and insufficient molecular specificity.
- p-value P < 0.0001
APA
Jiang Z, Tan H, et al. (2026). PSMA-targeted fluorescent probe for NIR-II imaging in prostate cancer intraoperative navigation and tumor margin mapping.. Theranostics, 16(9), 4551-4565. https://doi.org/10.7150/thno.117540
MLA
Jiang Z, et al.. "PSMA-targeted fluorescent probe for NIR-II imaging in prostate cancer intraoperative navigation and tumor margin mapping.." Theranostics, vol. 16, no. 9, 2026, pp. 4551-4565.
PMID
41799210
Abstract
[UNLABELLED] Accurate delineation of tumor margins during prostate cancer surgery remains challenging due to limited intraoperative visualization and insufficient molecular specificity. Here, we developed a PSMA-targeted near-infrared fluorescent probe, PSMA-12-IRDye800CW, that leverages the clinically used IRDye800CW scaffold and its extended emission tail beyond 1000 nm to support NIR-II fluorescence imaging for intraoperative navigation and histopathological margin mapping.
[METHODS] PSMA-12-IRDye800CW integrates a PSMA-targeting ligand with an albumin-binding linker to enable active targeting and circulation-assisted tumor accumulation. Optical properties, targeting specificity, imaging performance, and biosafety were evaluated , in prostate cancer xenograft models with direct comparison to indocyanine green (ICG) across defined time points, and in clinical formalin-fixed paraffin-embedded (FFPE) prostate specimens with matched histopathology and PSMA immunohistochemistry.
[RESULTS] In 22Rv1 (PSMA⁺) xenografts, PSMA-12-IRDye800CW achieved significantly higher tumor-to-background ratios than ICG at key surgical-relevant time points, including 24 h (4.31 ± 0.17 vs. 2.65 ± 0.15), providing a practical imaging window for fluorescence-guided resection. tissue analyses further confirmed significantly higher fluorescence in tumors than in muscle and skin. In human FFPE specimens, fluorescence showed pathology-aligned spatial correspondence with PSMA immunohistochemistry, and fluorescence intensity correlated strongly with PSMA H-scores (R² = 0.8616, P < 0.0001), enabling micron-scale histopathological margin mapping. Multimodal biosafety assessments indicated favorable biocompatibility with no evident acute toxicity and low immunogenic potential.
[CONCLUSIONS] PSMA-12-IRDye800CW enables NIR-II fluorescence imaging-assisted intraoperative navigation and provides a quantitative, pathology-anchored readout for histopathological margin mapping in prostate cancer, supporting further clinical validation of this PSMA-targeted strategy for fluorescence-guided surgery and margin assessment.
[METHODS] PSMA-12-IRDye800CW integrates a PSMA-targeting ligand with an albumin-binding linker to enable active targeting and circulation-assisted tumor accumulation. Optical properties, targeting specificity, imaging performance, and biosafety were evaluated , in prostate cancer xenograft models with direct comparison to indocyanine green (ICG) across defined time points, and in clinical formalin-fixed paraffin-embedded (FFPE) prostate specimens with matched histopathology and PSMA immunohistochemistry.
[RESULTS] In 22Rv1 (PSMA⁺) xenografts, PSMA-12-IRDye800CW achieved significantly higher tumor-to-background ratios than ICG at key surgical-relevant time points, including 24 h (4.31 ± 0.17 vs. 2.65 ± 0.15), providing a practical imaging window for fluorescence-guided resection. tissue analyses further confirmed significantly higher fluorescence in tumors than in muscle and skin. In human FFPE specimens, fluorescence showed pathology-aligned spatial correspondence with PSMA immunohistochemistry, and fluorescence intensity correlated strongly with PSMA H-scores (R² = 0.8616, P < 0.0001), enabling micron-scale histopathological margin mapping. Multimodal biosafety assessments indicated favorable biocompatibility with no evident acute toxicity and low immunogenic potential.
[CONCLUSIONS] PSMA-12-IRDye800CW enables NIR-II fluorescence imaging-assisted intraoperative navigation and provides a quantitative, pathology-anchored readout for histopathological margin mapping in prostate cancer, supporting further clinical validation of this PSMA-targeted strategy for fluorescence-guided surgery and margin assessment.
MeSH Terms
Male; Prostatic Neoplasms; Humans; Animals; Fluorescent Dyes; Glutamate Carboxypeptidase II; Antigens, Surface; Optical Imaging; Mice; Disease Models, Animal; Surgery, Computer-Assisted; Cell Line, Tumor; Margins of Excision; Benzenesulfonates; Indoles
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