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

Maryana Handula, Marjolein Verhoeven, Kuo Ting Chen, Joost Haeck, Marion de Jong, Simone U. Dalm, Yann Seimbille*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
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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 [111 In]In-12 and [111 In]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.

Original languageEnglish
Article number195
JournalPharmaceutics
Volume14
Issue number1
DOIs
Publication statusPublished - 14 Jan 2022

Bibliographical note

Funding Information:
Funding: This research was funded by the Dutch cancer society (KWF), grant numbers YIG11671 and 12259.

Funding Information:
Acknowledgments: The authors are grateful to the Dutch cancer society (KWF) for the financial support and the department of Radiology and Nuclear Medicine at the Erasmus MC for the technical assistance. This work was supported through the use of imaging equipment provided by the Applied Molecular Imaging Erasmus MC facility.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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