Near-infrared fatty acid molecular probe for image-guided surgery of glioblastoma.

Abstract

Metabolic reprogramming is considered a major driving factor in cancer growth and yet it remains challenging to monitor in vivo uptake of fatty acids, which are essential energy sources for many tumor types. Here, we report the development of a novel, long-chain fatty acid (FA), near-infrared (NIR) imaging reagent (FA-ICG) for real-time, non-invasive imaging of FA absorption in vitro and in vivo. Moreover, we demonstrate the application of the probe in image-guided cancer surgery, where precise assessment of tumor margins is paramount for removal. Specifically, we focus on glioblastoma (GBM), where FA metabolism plays a key role in progression and where there is a significant need for better intraoperative imaging. Here, we successfully demonstrate the application of the probe for NIR in vivo imaging in two different orthotopic models of GBM. In addition, we validate the uptake of the probe in companion dogs with mastocytomas, as these develop cancer with a similar pathology to humans. Our results demonstrate that the probe combines benefits from NIR imaging, such as high sensitivity, low autofluorescence, and deep tissue penetration, with specific tumor metabolism-based targeting and retention. Thus, it represents a promising candidate for a wide range of applications in the fields of metabolic imaging, drug development, and most notably for translation in image-guided surgery.