Emerging Radioligands as Tools to Track Multi-Organ Senescence

Area of Science:

• Gerontology
• Molecular Imaging
• Biomarker Discovery

Background:

• Cellular senescence, characterized by the senescence-associated secretory phenotype (SASP), drives aging, organ dysfunction, and chronic diseases.
• Accumulation of senescent cells promotes inflammation, fibrosis, and metabolic disruption.
• Non-invasive detection of senescence is challenging due to its heterogeneity and lack of universal biomarkers.

Purpose of the Study:

• To review novel positron emission tomography (PET) radioligands targeting hallmark features of senescence.
• To explore the potential of these probes for in vivo visualization, tracking, and measurement of senescence.
• To highlight their translation into clinical interventions for early diagnosis and monitoring of senescence-driven pathologies.

Main Methods:

• Review of recent advances in PET imaging probes for senescence.
• Focus on tracers targeting specific senescence pathways, such as β-galactosidase ([18F]FPyGal) and fibroblast activation protein (FAP).
• Integration of organ-specific imaging biomarkers with molecular insights.

Main Results:

• [18F]FPyGal shows selective accumulation in senescent cells in preclinical and early clinical studies.
• FAP-targeted radioligands are emerging for imaging fibrotic remodeling in various organs.
• New PET probes demonstrate potential for in vivo visualization and quantification of senescence.

Conclusions:

• Novel PET radioligands offer a promising avenue for non-invasive detection and monitoring of cellular senescence.
• These imaging tools can facilitate early diagnosis and personalized management of age-related diseases.
• Integrating PET imaging with molecular insights is poised to transform the treatment of senescence-driven pathologies.