25 August 2021

Sandra Heskamp, Yvonne Derks and colleagues, developed a novel PSMA-targeting ligand, optimized for multimodal image-guided PCa surgery combined with targeted photodynamic therapy and published the these findings in the Theranostics.

Incomplete resection of prostate cancer (PCa) occurs in 15%-50% of patients, which can lead to disease recurrence. To improve outcome for PCa patients, new approaches to increase the chance of complete resection of all tumor tissue is required. PCa cells are characterized by overexpression of prostate-specific membrane antigen (PSMA). PSMA targeting ligands labeled with both a radionuclide and photosensitizer can potentially be used to improve intra-operative PCa detection and treatment.


Here, we developed and characterized dual labeled [111In]In-DOTA(GA)-IRDye700DX-PSMA ligands, varying in their molecular composition, for use in intraoperative radiodetection, fluorescence imaging and targeted photodynamic therapy of PCa lesions. PSMA-specificity of these ligands was determined in xenograft tumor models and on fresh human PCa biopsies.


Ligand structure optimization showed that addition of the photosensitizer (IRDye700DX) and additional negative charges significantly increased ligand uptake in PSMA-expressing tumors. Moreover, an ex vivo incubation study on human tumor biopsies confirmed the PSMA-specificity of these ligands on human samples, bridging the gap to the clinical situation.


We developed a novel PSMA-targeting ligand, optimized for multimodal image-guided PCa surgery combined with targeted photodynamic therapy. Currently, we are in the preparatory phase of producing this dual-labelled PSMA ligand for clinical use in PCa patients.  

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