Pre- and Intraoperative Visualization of GRPR-Expressing Solid Tumors: Preclinical Profiling of Novel Dual-Modality Probes for Nuclear and Fluorescence Imaging.
Cancers (Basel)
; 15(7)2023 Apr 05.
Article
em En
| MEDLINE
| ID: mdl-37046825
ABSTRACT
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 [111In]In-12-15 were performed in nude mice bearing a PC-3 and NCI-H69 xenograft, and showed that the probe with only a pADA 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cancers (Basel)
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Holanda