# Targeted Phase-change Nanodroplets for Translatable Molecular Ultrasound Imaging of Micrometastases

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $203,428

## Abstract

Determination of malignant spread is the key prognostic factor for oral-cavity cancer and is critical for the
development of an adequate treatment plan. Metastases are the primary driver behind over 6,400 annual deaths
and a five-year survival rate of only 66% for oral-cavity cancer in America. Thus, accurate and timely assessment
of the presence of micrometastases (mMets) is critical for accurate staging and therapy planning.
Despite its
significant potential morbidity, elective neck dissection (END) is the gold standard for assessing the presence
or absence of disease in sentinel lymph nodes (SLNs), the most common location for oral-cavity cancer mMets.
Unfortunately, there is currently no effective preoperative or intraoperative method to detect such mMets, and
thus there is an urgent clinical need for a point-of-care imaging technology that can be safely and noninvasively
implemented to reliably visualize mMets in real-time. The goal of our research is to develop a targeted contrast
agent and a noninvasive imaging technique to accurately identify mMets in SLNs with high resolution, a method
we refer to as targeted activatable nanodroplet (TAN) molecular ultrasound lymphatic (MUSL) imaging. Our
imaging approach promises to deliver a uniquely versatile contrast agent that has a size profile that can be
remotely adjusted to allow for both molecularly targeted delivery, requiring a nano-scale agent, and high-contrast,
high-resolution imaging at depth with conventional ultrasound, which requires a micron-scale agent. A highly
appealing feature of our technology is its use of widely available conventional US imaging with a single injection
of an inert and highly biocompatible contrast agent, attributes that support widespread clinical implementation.
Our hypothesis is that TANs can be imaged in real-time and with high contrast and resolution using conventional
US imaging, yielding immediate diagnostic information for patient staging that will facilitate timely and less-
invasive treatment (e.g., eliminate ENDs) and/or to intraoperatively guide surgical/biopsy interventions. Our
compelling preliminary data demonstrate synthesis feasibility of stable, nano-sized, molecularly specific TANs
that can undergo an ultrasound (US) activatable phase-change transformation to their microbubble (MB) form
(~1 ?m), which can be visualized using conventional US imaging. To develop this technology toward detection
of SLN mMets from head and neck cancers, we will pursue the following aims: (SA1) develop clinically
translatable TANs with optimum acoustic-activation thresholds and with demonstrated molecular specificity to
head and neck cancer cells; (SA2) optimize MUSL imaging for high-resolution, quantitative assessment of
targeted TANs in cell phantoms; (SA3) validate TAN-MUSL imaging’s ability to detect SLN mMets in an
orthotopic murine model of metastatic cancer. This platform has potential to address all disadvantages of the
current standard of care by providing...

## Key facts

- **NIH application ID:** 9830624
- **Project number:** 5R21CA234526-02
- **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:** 2020
- **Award amount:** $203,428
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830624

## Citation

> US National Institutes of Health, RePORTER application 9830624, Targeted Phase-change Nanodroplets for Translatable Molecular Ultrasound Imaging of Micrometastases (5R21CA234526-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830624. Licensed CC0.

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