# Compositions and methods for enhanced fluorine-19 magnetic resonance imaging cell tracking

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $537,526

## Abstract

A common need for clinical developers of cell therapies, such as immunotherapeutic and stem cells, is a non-
invasive means to visualize the fate of cells following injection. Imaging of cell trafficking can provide critical
feedback regarding the persistence, motility, optimal routes of delivery and therapeutic doses. This project aims
to synthesize and biologically evaluate innovative new imaging probes for sensitive in vivo cell tracking using
fluorine-19 (19F) magnetic resonance imaging (MRI). We will advance the formulation science of a compelling
new class of ‘metallo-perfluorocarbon’ (MPFC) nanoemulsion imaging probes. These agents will be a key
element to a multi-pronged strategy to advance cell detection sensitivity by an order of magnitude over current
19F MRI cell detection technologies. Overall, in 19F cell tracking, cell populations of interest are initially labeled in
culture using perfluorocarbon nanoemulsions. Following transfer to the subject, cells are tracked in vivo using
19F MRI. The fluorine inside the cells yields cell-specific images, with no background signal. One of the
bottlenecks preventing the broader adoption of 19F based cell tracking is sensitivity limits to sparse cell numbers.
The sensitivity of this technology can be improved by a three-pronged approach: (1) molecular design and
synthesis to improve the intrinsic sensitivity of the molecular signal generator and (2) nanoemulsion probe
formulation with cell targeting to enhance intracellular delivery and uptake, and (3) employing MRI data
acquisition schemes that have a more efficient signal-to-noise ratio per acquisition time (SNR/t). Recent results
have demonstrated dramatically-enhanced sensitivity of fluorine MRI by molecular design. We have created a
new class of molecules that combine highly fluorinated nanoemulsions with the magnetic properties of metals
that are solubilized into the fluorous phase. Solubilized paramagnetic metal ions provide a dramatic reduction in
the 19F spin-lattice relaxation time thereby enhancing SNR/t and cell detection sensitivity. It was discovered that
iron is most effective metal at enhancing the fluorine MRI signal. Building on these preliminary results, the
proposal has four Specific Aims: Aim 1. Chelation strategies for MPFCs. We will evaluate a range of suitable
chelate molecules and synthesis strategies to stably incorporate metal ions into PFC. Aim 2. Enhanced cell
delivery of MPFC nanoemulsion using cell penetrating peptides (CPPs). Successful MRI detection of cells
critically requires optimal intracellular delivery of emulsified MPFC ex vivo. We will develop novel MPFC
nanoemulsion formulations incorporating CPPs attached to the nanoemulsion surfactant to rapidly and optimally
label cells for cell tracking. Aim 3. “Smart” in vivo targeted nanoemulsions. As an exploratory extension of this
work, we devise MPFC nanoemulsions that target tumors in vivo. Aim 4. In vivo imaging methods to track
immunotherapeutic T cells in c...

## Key facts

- **NIH application ID:** 9893716
- **Project number:** 5R01EB024015-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** ERIC T. AHRENS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $537,526
- **Award type:** 5
- **Project period:** 2017-04-15 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893716

## Citation

> US National Institutes of Health, RePORTER application 9893716, Compositions and methods for enhanced fluorine-19 magnetic resonance imaging cell tracking (5R01EB024015-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893716. Licensed CC0.

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