# PET Probes for Senescence Detection in Brain

> **NIH NIH R41** · SENOTRAC BIOTECHNOLOGY LLC · 2022 · $293,317

## Abstract

PROJECT SUMMARY
 Around 50 million people worldwide are suffering from Alzheimer’s disease (AD) and related dementias,
and AD is observed primarily in aged people. Current diagnosis of AD relies primarily on observations of
declines in mental and cognitive functions, when irreversible brain damage occurs. Positron emission
tomography (PET) tracers for early diagnosis of AD have been developed via assessing Aβ or tau levels,
however aggregate-targeting tracers often suffer from high nonspecific binding. Therefore, there is an urgent
need for developing novel tools targeting molecular level to improve the specificity of early diagnosis of AD.
 Cellular senescence has been shown to be a critical contributor disrupting the homeostasis and functions of
aging brains. In aged brains, senescent cells accumulate and exert chronic inflammatory pressure on
surrounding cells. Higher levels of senescence in different types of brain cells have been observed in mice and
human with AD and selective removal of senescent cells reduces Aβ plaque formation in mouse brain and
improves cognitive functions. These findings indicate that senescence can potentially serve as an early indicator
and therapeutic target for AD. However, tools for real-time in vivo senescence detection are extremely limited.
Recently, the Cui group at the University of Florida (UF) has developed a series of activatable molecular probes,
enabling the successful real-time imaging of senescence in animal models for the first time. These probes have
high detection sensitivity produced by a self-immobilizing moiety installed on the probe so that upon activation,
the probe can be covalently linked to surrounding proteins at the site of activation.
 Based on this strategy, SenoTrac, partnering with UF and Moffitt Cancer Center, aims to develop the first-
in-class PET probes for senescence. Briefly, the novel PET probe will consist of a β-galactoside that can be
specifically cleaved by senescence-associated β-galactosidase (SA-β-gal), a 18F, and a self-immobilizing
moiety that can anchor the probe onto surrounding proteins upon activation. We expect the activatable PET
probe to have high brain uptake, minimal diffusion and high signal/background contrast with excellent spatial
resolution. We will characterize these probes in vitro (SenoTrac and UF), and we will also evaluate their ability
to cross the blood brain barrier in animals (UF). Radiochemistry before PET imaging will be carried at Moffitt.
AD mouse model (5xFAD) will be used in the dynamic PET/CT scan to see the levels of senescence in
different age groups. Additionally, we will clear senescent cells using senolytics, perform PET imaging of
senescence and evaluate AD phenotypes in these mice. Ex vivo analysis of the brain tissues will provide
information of other AD and senescence biomarkers (UF). We expect to draw correlation of senescence levels
and various AD phenotypes. In Phase 1, we will develop the PET probes for senescence tracking in ...

## Key facts

- **NIH application ID:** 10603859
- **Project number:** 1R41AG081007-01
- **Recipient organization:** SENOTRAC BIOTECHNOLOGY LLC
- **Principal Investigator:** Lina Cui
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $293,317
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10603859

## Citation

> US National Institutes of Health, RePORTER application 10603859, PET Probes for Senescence Detection in Brain (1R41AG081007-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10603859. Licensed CC0.

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