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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2014

01-12-2014 | Translational Research and Biomarkers

Near-Infrared Fluorescence Imaging of Both Colorectal Cancer and Ureters Using a Low-Dose Integrin Targeted Probe

Authors: Floris P. R. Verbeek, MSc, Joost R. van der Vorst, MD, Quirijn R. J. G. Tummers, MD, Martin C. Boonstra, BSc, Karien E. de Rooij, PhD, Clemens W. G. M. Löwik, PhD, A. Rob P. M. Valentijn, PhD, Cornelis J. H. van de Velde, MD, PhD, Hak Soo Choi, PhD, John V. Frangioni, MD, PhD, Alexander L. Vahrmeijer, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 4/2014

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Abstract

Background

Irradical tumor resections and iatrogenic ureteral injury remain a significant problem during lower abdominal surgery. The aim of the current study was to intraoperatively identify both colorectal tumors and ureters in subcutaneous and orthotopic animal models using cRGD-ZW800-1 and near-infrared (NIR) fluorescence.

Methods

The zwitterionic fluorophore ZW800-1 was conjugated to the tumor specific peptide cRGD (targeting integrins) and to the a-specific peptide cRAD. One nmol cRGD-ZW800-1, cRAD-ZW800-1, or ZW800-1 alone was injected in mice bearing subcutaneous HT-29 human colorectal tumors. Subsequently, cRGD-ZW800-1 was injected at dosages of 0.25 and 1 nmol in mice bearing orthotopic HT-29 tumors transfected with luciferase2. In vivo biodistribution and ureteral visualization were investigated in rats. Fluorescence was measured intraoperatively at several time points after probe administration using the FLARE imaging system.

Results

Both subcutaneous and orthotopic tumors could be clearly identified using cRGD-ZW800-1. A significantly higher signal-to-background ratio was observed in mice injected with cRGD-ZW800-1 (2.42 ± 0.77) compared with mice injected with cRAD-ZW800-1 or ZW800-1 alone (1.21 ± 0.19 and 1.34 ± 0.19, respectively) when measured at 24 h after probe administration. The clearance of cRGD-ZW800-1 permitted visualization of the ureters and also generated minimal background fluorescence in the gastrointestinal tract.

Conclusions

This study appears to be the first to demonstrate both clear tumor demarcation and ureteral visualization after a single intravenous injection of a targeted NIR fluorophore. As a low dose of cRGD-ZW800-1 provided clear tumor identification, clinical translation of these results should be possible.
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Metadata
Title
Near-Infrared Fluorescence Imaging of Both Colorectal Cancer and Ureters Using a Low-Dose Integrin Targeted Probe
Authors
Floris P. R. Verbeek, MSc
Joost R. van der Vorst, MD
Quirijn R. J. G. Tummers, MD
Martin C. Boonstra, BSc
Karien E. de Rooij, PhD
Clemens W. G. M. Löwik, PhD
A. Rob P. M. Valentijn, PhD
Cornelis J. H. van de Velde, MD, PhD
Hak Soo Choi, PhD
John V. Frangioni, MD, PhD
Alexander L. Vahrmeijer, MD, PhD
Publication date
01-12-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 4/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3524-x

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