Towards Complete Tumor Resection: Novel Dual-Modality Probes for Improved Image-Guided Surgery of GRPR-Expressing Prostate Cancer

Pharmaceutics

Joost Haeck¹  Kuo-Ting Chen²  Marjolein Verhoeven³  Maryana Handula³  Simone U. Dalm³  Yann Seimbille³  Marion de Jong³ 

[1] AMIE Core Facility, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands;Department of Chemistry, National Dong Hwa University, Shoufeng, Hualien 974301, Taiwan;Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands;

关键词: prostate cancer;    PC-3;    GRPR;    NeoB;    dual-modality imaging;    IEDDA;   

DOI  :  10.3390/pharmaceutics14010195

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown