Issue 12, 2022

Design and characterization of fibroblast activation protein targeted pan-cancer imaging agent for fluorescence-guided surgery of solid tumors

Abstract

Tumor-targeted fluorescent dyes have been shown to significantly improve a surgeon's ability to locate and resect occult malignant lesions, thereby enhancing a patient's chances of long term survival. Although several tumor-targeted fluorescent dyes have been developed for imaging specific subsets of human cancers, no tumor-targeted dye has been designed that can image all cancer types. Based on observations that fibroblast activation protein (FAP) is upregulated on cancer-associated fibroblasts (CAFs) that infiltrate essentially all solid tumors, we have undertaken to develop a FAP-targeted fluorescent dye that can image CAFs without accumulating in healthy cells or fibroblasts. We report here that FTL-S-S0456, a novel FAP-targeted near infrared dye that binds FAP with high affinity (∼12 nM) and specificity (>5000-fold over PREP and DPP-IV), concentrates in all seven solid tumor types examined, yielding fluorescence images with high tumor to background ratios that persist for several days. We conclude that FTL-S-S0456 constitutes an excellent ligand-targeted near infrared dye that enables intra-operative imaging of most if not all solid tumors.

Graphical abstract: Design and characterization of fibroblast activation protein targeted pan-cancer imaging agent for fluorescence-guided surgery of solid tumors

Supplementary files

Article information

Article type
Paper
Submitted
01 Dec 2021
Accepted
20 Feb 2022
First published
22 Feb 2022

J. Mater. Chem. B, 2022,10, 2038-2046

Design and characterization of fibroblast activation protein targeted pan-cancer imaging agent for fluorescence-guided surgery of solid tumors

R. Mukkamala, S. D. Lindeman, K. A. Kragness, I. Shahriar, M. Srinivasarao and P. S. Low, J. Mater. Chem. B, 2022, 10, 2038 DOI: 10.1039/D1TB02651H

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