# Development of fluorinated dyes for deeper tissue photoacoustic imaging with phase changing nanodroplets

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2022 · $243,000

## Abstract

Abstract. Photoacoustic imaging (PAI) is a promising modality that is non-ionizing, low-cost, and offers high-
contrast and high-spatiotemporal-resolution imaging in a platform that is amenable for high-throughput preclinical
use and for specific clinical applications. However, widespread use of molecular PAI is severely limited by
availability of validated contrast agents. Currently available contrast agents either do not have adequate
photostability under the pulsed illumination that is required for PAI, lack sufficient PAI-signal-generation ability
for deep imaging, or their absorbance spectra significantly overlap with those of hemoglobin, which reduces
imaging sensitivity. In order to address these limitations, a new class of PAI contrast agents was proposed that
is based on phase-changing perfluorocarbon (PFC) nanodroplets (NDs). These agents are based on a liquid
PFC core and a light-absorbing “fuse” in the form of a dye or a nanoparticle. Illumination of these NDs with a
pulsed laser triggers liquid-to-gas transition of the PFC core heated by light-absorbing chromophores that results
in a very strong PAI signal. Therefore, these agents are often referred to as Laser-Activated NDs (LANDs).
Furthermore, after laser excitation PFC microbubbles can re-condense back into their liquid nanodroplet form,
which can allow multiple excitations and the possibility for dynamic imaging contrast and super-resolution PAI.
However, evaluation of this exciting contrast agent design by multiple research groups revealed one critical
limitation – commonly used dye molecules or nanoparticles are not soluble or mixable with perfluorocarbons.
Therefore, current LANDs contain their “fuses” (i.e., dye absorbers) in the shell with a loading efficiency and
distribution of the dyes that is highly variable depending on specifics of a LAND's coating and a dye's chemical
structure. Importantly, in addition to the limitations associated with irreproducibility and a shot shelf-life of LANDs
due to leakage of dye molecules from a LAND's shell, recent studies of phase-changing NDs showed the
advantage of heating LANDs from within the core for an effective liquid-to-gas transition. These data underline
the importance of heating inside an ND's core for activation of LANDs that cannot be effectively achieved with
peripherally located chromophores. Here we propose to address weaknesses of the prior research by developing
fluorinated dyes with absorbance in the first and second near-infrared tissue windows (NIR-I and NIR-II). Our
hypothesis is that the fluorinated dyes will be soluble inside the PFC core, thus resulting in highly reproducible,
stable LAND formulations with greatly improved laser activation efficacy. To reflect these advancements in LAND
formulation, we refer to PFC NDs doped with fluorinated dyes as enhanced LANDs (eLANDs). We posit that an
increase in concentration of uniformly distributed fluorinated dyes inside the PFC core will dramatically improve
efficacy ...

## Key facts

- **NIH application ID:** 10439866
- **Project number:** 5R21EB030805-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Richard R. Bouchard
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $243,000
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439866

## Citation

> US National Institutes of Health, RePORTER application 10439866, Development of fluorinated dyes for deeper tissue photoacoustic imaging with phase changing nanodroplets (5R21EB030805-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10439866. Licensed CC0.

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