Project Summary/Abstract
Biomedical imaging is an essential modality used in clinical diagnosis. Common imaging
modalities such as magnetic resonance imaging (MRI), X-ray imaging, and positron emission
tomography (PET), are constrained by cost, acquisition time, and/or use of ionizing radiation.
Fluorescence imaging is an optimal modality for biomedical imaging, as it is non-invasive,
inexpensive, and safe for living systems. Presently, fluorescence imaging uses near-infrared light
(NIR, 700–1000 nm), but the shortwave infrared region (SWIR, 1000–2000 nm) of the
electromagnetic spectrum has emerged as a superior region for fluorescence imaging.
Advantages such as the reduced light scattering and increased tissue penetration of these lower
energy photons, leads to dramatic increases in contrast compared to the NIR and drives
innovation for SWIR fluorophores. Our group recently developed a bright flavylium-based SWIR
polymethine dye named Flav7. However, the growing field would benefit from even brighter and
deeply red-shifted fluorophores. In order to fine-tune flavylium dyes for effective imaging in living
systems, an investigation of structural changes and corresponding photophysical properties is
necessary. Through systematic derivatization of the Flav7 scaffold, this work seeks to elucidate
design principles for the development of a SWIR F¿rster resonance energy transfer (FRET) turn-
on probe. FRET probes are of great interest for imaging as they can lead to greater signal-to-
noise ratios compared to free dyes. Our lab aims to recruit SWIR FRET pairs for improved
biomedical imaging applications. Using a precedented protease cleavable linker, we will
synthesize a SWIR FRET probe for image guided surgery of small tissue sarcoma (STS). The
development of a FRET probe reliant on tissue-penetrating SWIR light will greatly improve clinical
diagnosis.