Molecular Tuning of IR-786 for Improved Brown Adipose Tissue Imaging

To overcome the limitations of brown adipose tissue (BAT) imaging with MRI and PET/CT, near-infrared (NIR) fluorescence imaging has been utilized in living animals because it is highly sensitive, noninvasive, nonradioactive, and cost-effective. To date, only a few NIR fluorescent dyes for detecting BAT have been reported based on the structure-inherent targeting strategy. Among them, IR-786, a commercial cyanine dye, was used firstly for quantitative NIR imaging of BAT perfusion in 2003. Owing to the high cytotoxicity, poor water solubility, and strong nonspecific background uptake of IR-786, the chemical structure of IR-786 should be redesigned to be more hydrophilic and less toxic so that it can show more BAT-specific accumulation. Here, we developed a BAT-specific NIR dye, BF800-AM, by incorporating the tyramine linker in the original structure of IR-786. After modifying the physicochemical properties of IR-786, in vivo results showed significant uptake of the newly designed BF800-AM in the BAT with improved signal-to-background ratio. Additional in vivo studies using mouse tumor models revealed that BF800-AM targeting to BAT is independent of tumor tissues, as distinct from IR-786 showing uptake in both tissues. Therefore, BF800-AM can be used for improved noninvasive visualization of BAT mass and activity in living animals.

Automated summary

To overcome the limitations of current methods for imaging brown adipose tissue (BAT), researchers have developed a new near-infrared (NIR) dye called BF800-AM. This dye is more hydrophilic and less toxic than the previously used dye IR-786. In vivo studies have shown that BF800-AM has a significant uptake in BAT with improved signal-to-background ratio, making it a promising tool for noninvasive visualization of BAT mass and activity.