First-in-Human Assessment of cRGD-ZW800-1, a Zwitterionic, Integrin-Targeted, Near-Infrared Fluorescent Peptide in Colon Carcinoma

Kim S. de Valk, Marion M. Deken, Henricus J.M. Handgraaf, Shadhvi S. Bhairosingh, Okker D. Bijlstra, Michiel J. van Esdonk, Anton G.T. Terwisscha van Scheltinga, A. Rob P.M. Valentijn, Taryn L. March, Jaap Vuijk, Koen C.M.J. Peeters, Fabian A. Holman, Denise E. Hilling, J. Sven D. Mieog, John V. Frangioni, Jacobus Burggraaf, Alexander L. Vahrmeijer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

64 Citations (Scopus)

Abstract

Purpose: 

Incomplete oncologic resections and damage to vital structures during colorectal cancer surgery increases morbidity and mortality. Moreover, neoadjuvant chemoradiotherapy has become the standard treatment modality for locally advanced rectal cancer, where subsequent downstaging can make identification of the primary tumor more challenging during surgery. Near-infrared (NIR) fluorescence imaging can aid surgeons by providing real-time visualization of tumors and vital structures during surgery. 

Experimental Design: 

We present the first-in-human clinical experience of a novel NIR fluorescent peptide, cRGD-ZW800-1, for the detection of colon cancer. cRGD-ZW800-1 was engineered to have an overall zwitterionic chemical structure and neutral charge to lower nonspecific uptake and thus background fluorescent signal.

resection, assessing 0.005, 0.015, and 0.05 mg/kg cRGD-ZW800-1 for the intraoperative visualization of colon cancer. 

Results: 

cRGD-ZW800-1 appears safe, and exhibited rapid elimination into urine after a single low intravenous dose. Minimal invasive intraoperative visualization of colon cancer through full-thickness bowel wall was possible after an intravenous bolus injection of 0.05 mg/kg at least 2 hours prior to surgery. Longer intervals between injection and imaging improved the tumor-to-background ratio.

Conclusions: 

cRGD-ZW800-1 enabled fluorescence imaging of colon cancer in both open and minimal invasive surgeries. Further development of cRGD-ZW800-1 for widespread use in cancer surgery may be warranted given the ubiquitous overexpression of various integrins on different types of tumors and their vasculature.

Original languageEnglish
Pages (from-to)3990-3998
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number15
DOIs
Publication statusPublished - 1 Aug 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
©2020 American Association for Cancer Research.

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