# Cellular Senescence Network: New Imaging Tools for Arthritis Imaging

> **NIH NIH UH3** · STANFORD UNIVERSITY · 2024 · $646,656

## Abstract

Cellular Senescence Network: New Imaging Tools for Arthritis Imaging
Senescent cells play a key role in the pathogenesis of major musculoskeletal diseases, such as chonic
inflammatory joint disorders, rheumatoid arthritis (RA) and osteoarthritis (OA). Cellular senescence in articular
joints represents a response of local cells to persistent stress that leads to cell-cycle arrest and enhanced
production of inflammatory cytokines, which in turn perpetuates joint damage and leads to significant
morbidities of afflicted patients. It has been recently discovered that clearance of senescent cells by novel
“senolytic” therapies can attenuate the chronic inflammatory microenvironment of RA and OA, and thereby,
prevent further disease progression and support healing processes. In order to identify patients who might
benefit from these new senolytic therapies and to monitor therapy response, there is a significant unmet need
in identifying and mapping of senescent cells in articular joints and related musculoskeletal tissues. To fill this
gap, we propose to develop a new imaging biomarker that will significantly improve our capabilities to identify
and characterize senescent cells in human musculoskeletal tissues. We have generated exciting preliminary
data that show that 3-D-galacto-2-nitropyridine (PyGal), a known hydrophilic b-gal substrate, can be labeled
with 18F-fluorine. Upon intravenous injection, 18F-PyGal enters senescent cells and is selectively cleaved by b-
galactosidase, a senescence-specific enzyme in these cells. The trapped radiotracer can be detected with
positron emission tomography (PET) and autoradiography, thereby serving as an imaging biomarker for
senescent cells. We propose to introduce 18F-PyGal as the first clinically translatable radiotracer which
can detect senescent cells in vivo, in bones and joints of animal models and human volunteers. In the
initial UG3 phase of our project, we will demonstrate proof-of-principle of this new imaging technology in a
mouse model of RA and a large animal model of OA. In the subsequent UH3 phase, we will scale, optimize
and validate 18F-PyGal PET for mapping human tissues, first in human joint specimen and second in a first-in-
human phase I clinical trial. At the end of the UH3 phase, we will have delivered a novel imaging tool that can
visualize and quantify the presence and distribution of senescent cells in multiple musculoskeletal tissues
directly, non-invasively and longitudinally in vivo. Results will be catalogized in a planned senescence cell atlas
and shared with the cellular senescence network. Our 18F-PyGal-PET imaging tool will significantly improve
upon state-of-the-art imaging technologies for the diagnosis of musculoskeletal disorders, can be integrated
with other imaging technologies, such as MRI, and is ultimately capable of being scaled to map senescent cells
in multiple human tissues in a high-throughput fashion. Since 18F-PyGal targets senescent cells in multiple
different...

## Key facts

- **NIH application ID:** 10919233
- **Project number:** 5UH3CA268112-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Heike Elizabeth Daldrup-Link
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $646,656
- **Award type:** 5
- **Project period:** 2021-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919233

## Citation

> US National Institutes of Health, RePORTER application 10919233, Cellular Senescence Network: New Imaging Tools for Arthritis Imaging (5UH3CA268112-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10919233. Licensed CC0.

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