Pre- and Intraoperative Visualization of GRPR-Expressing Solid Tumors: Preclinical Profiling of Novel Dual-Modality Probes for Nuclear and Fluorescence Imaging

• Published in: Cancers Vol. 15; no. 7; p. 2161
• Main Authors: Verhoeven, Marjolein, Handula, Maryana, van den Brink, Lilian, de Ridder, Corrina M A, Stuurman, Debra C, Seimbille, Yann, Dalm, Simone U
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.04.2023; MDPI
• Subjects: Biodistribution; Care and treatment; Cell receptors; Chromatography; Diagnostic imaging; FDA approval; Fluorescent indicators; Gastrin; Gastrin-releasing peptide; Localization; Methods; Optimization; Peptides; Physiological aspects; Prostate; Prostate cancer; Solid tumors; Surgery; Tumors; Netherlands; United Kingdom > UK; United States > US; image-guided surgery; dual-modality probe; optical imaging; SPECT imaging; multi-modality imaging; NeoB; gastrin-releasing peptide receptor (GRPR)
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15072161

Image-guided surgery using a gastrin-releasing peptide receptor (GRPR)-targeting dual-modality probe could improve the accuracy of the resection of various solid tumors. The aim of this study was to further characterize our four previously developed GRPR-targeting dual-modality probes that vary in linker structures and were labeled with indium-111 and sulfo-cyanine 5. Cell uptake studies with GRPR-positive PC-3 cells and GRPR-negative NCI-H69 cells confirmed receptor specificity. Imaging and biodistribution studies at 4 and 24 h with 20 MBq/1 nmol [ In]In- - were performed in nude mice bearing a PC-3 and NCI-H69 xenograft, and showed that the probe with only a ADA linker in the backbone had the highest tumor-to-organ ratios (T/O) at 24 h after injection (T/O > 5 for, e.g., prostate, muscle and blood). For this probe, a dose optimization study with three doses (0.75, 1.25 and 1.75 nmol; 20 MBq) revealed that the maximum image contrast was achieved with the lowest dose. Subsequently, the probe was successfully used for tumor excision in a simulated image-guided surgery setting. Moreover, it demonstrated binding to tissue sections of human prostate, breast and gastro-intestinal stromal tumors. In summary, our findings demonstrate that the developed dual-modality probe has the potential to aid in the complete surgical removal of GRPR-positive tumors.