Issue 10, 2017

An agent for optical imaging of TrkC-expressing, breast cancer

Abstract

Tropomyosin receptor kinases receptor C is expressed at high levels on the surface of tumors from metastatic breast cancer, metastatic melanoma, glioblastoma, and neuroblastoma. Previous studies have shown synthetic TrkC ligands bearing agents for photodynamic therapy could be used to completely ablate 4T1 metastatic breast tumors and suppress metastatic spread in vivo. Modification of these probes (A in the text) to make them suitable for near infrared optical imaging in vivo would require a substantial increase in molecular mass (and hence increased vulnerability to undesirable absorption, metabolism and immunogenicity effects), or significant changes to the probe design which might compromise binding to TrkC in histochemical studies and on live cells. The research featured here was undertaken to investigate if the second strategy could be achieved without compromising binding to TrkC-expressing tissues. Specifically, an “aza-BODIPY” probe was synthesized to replace a spacer fragment in the original probe A. In the event, this new probe design (1a in the text) binds TrkC+ breast cancer in live cell cultures, in histochemical studies and in an in vivo murine model. Probe 1a binds TrkC+ tissues with good contrast with respect to healthy tissues, and much more strongly than an isomeric, non-TrkC binding, probe (1b) prepared as a negative control.

Graphical abstract: An agent for optical imaging of TrkC-expressing, breast cancer

Supplementary files

Article information

Article type
Research Article
Submitted
28 Jun 2017
Accepted
17 Aug 2017
First published
14 Sep 2017

Med. Chem. Commun., 2017,8, 1946-1952

An agent for optical imaging of TrkC-expressing, breast cancer

A. Kamkaew, F. Li, Z. Li and K. Burgess, Med. Chem. Commun., 2017, 8, 1946 DOI: 10.1039/C7MD00328E

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