# PET tracer for imaging senescence

> **NIH NIH R21** · STANFORD UNIVERSITY · 2024 · $194,579

## Abstract

PROJECT SUMMARY / ABSTRACT
 Senescence is a state of permanent cell cycle arrest, and can occur during development (programmed
senescence), or be triggered by a variety of stressors, like telomere shortening (defined as replicative
senescence), oxidative stress DNA damage, and oncogene activation (stress-induced premature senescence).
Senescent cells remain metabolically active and secrete high concentrations of signaling molecules into the
tissue microenvironment (known as Senescence-Associated Secretory Phenotype, or SASP). These secreted
factors can activate immune systems to initiate clearance of senescent cells, which contribute to tumor
suppression, would healing and tissue homeostasis. When the immunosurveillance fails to eliminate senescent
cells, their accumulation causes inflammation and contributes to a variety of diseases, including cancer,
metabolic disorders, fibrosis, diabetes, brain disorders, osteoarthritis, and kidney disease.
 These complex and important roles in ageing and diseases prompt extensive interest in developing
imaging methods to detect senescence cells. A number of optical imaging probes have been developed by
targeting senescence-associated beta-galactosidase (SA-b-gal) activity. However, their use in vivo is limited
due to poor penetration and scattering photons in living tissues. Several SPECT, MRI, and PET probes have
been reported to address this limitation, but they displayed either poor cell permeability and/or sensitivity. In
the case of PET tracers, they generally suffer from a lack of efficient signal retention mechanism.
 This research proposes to develop a novel PET tracer for in vivo imaging of senescence in a mouse
model of cancer by targeting a novel lysosomal enzyme and using an in celluo probe assembly retention
strategy. There are two Specific Aims: 1) synthesize the PET tracer and assess its capacity to detecting
senescence in cell culture; 2) validate the PET tracer in animal models of therapy induced senescence. This
project would provide a more specific and sensitive PET tracer for imaging cell senescence in vivo and for
future translation into human studies.

## Key facts

- **NIH application ID:** 10885191
- **Project number:** 5R21EB034967-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jianghong Rao
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,579
- **Award type:** 5
- **Project period:** 2023-07-10 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885191

## Citation

> US National Institutes of Health, RePORTER application 10885191, PET tracer for imaging senescence (5R21EB034967-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10885191. Licensed CC0.

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