# Emerging Radioligands as Tools to Track Multi-Organ Senescence

## TL;DR

This paper reviews new PET imaging tools that can detect and track cellular senescence in multiple organs, offering potential for early diagnosis and treatment of age-related diseases.

## Contribution

The paper introduces emerging radioligands for PET imaging that target senescence-associated pathways in various organs, enabling non-invasive tracking of senescence.

## Key findings

- [18F]FPyGal selectively accumulates in senescent cells in preclinical and clinical studies.
- FAP-targeted radioligands show promise for imaging fibrotic remodeling in multiple organs.
- PET radioligands can enable longitudinal monitoring of senescence-driven pathologies.

## Abstract

Senescence is a dynamic, multifaceted process implicated in tissue aging, organ dysfunction, and intricately associated with numerous chronic diseases. As senescent cells accumulate, they drive inflammation, fibrosis, and metabolic disruption through the senescence-associated secretory phenotype (SASP). Despite its clinical relevance, senescence remains challenging to detect non-invasively due to its heterogeneous nature and the lack of universal biomarkers. Recent advances in the development of specific imaging probes for positron emission tomography (PET) enable in vivo visualization of senescence-associated pathways across key organs, such as the lung, heart, kidney, and metabolic processes. For instance, [18F]FPyGal, a β-galactosidase-targeted tracer, has demonstrated selective accumulation in senescent cells in both preclinical and early clinical studies, while FAP-targeted radioligands are emerging as tools for imaging fibrotic remodeling in the lung, liver, kidney, and myocardium. This review examines a new generation of PET radioligands targeting hallmark features of senescence, with the potential to track and measure the process, the ability to be translated into clinical interventions for early diagnosis, and longitudinal monitoring of senescence-driven pathologies. By integrating organ-specific imaging biomarkers with molecular insights, PET probes are poised to transform our ability to manage and treat age-related diseases through personalized approaches.