Validation of in-vivo senescent cell imaging using the fluorine labelled β-galactosidase substrate, PyGal

Accumulation of senescent cells has been shown in recent years as a driver of most, if not all age-associated conditions. Drugs that selectively kill senescent cells (senolytics) emerged as novel therapeutic modalities for a wide range of age-associated diseases in pre-clinical studies, and first generation senolytics are now in about a dozen of clinical trials. The main limitations for translation are frequent side effects, limited specificity of first-generation senolytics, and importantly the absence of technologies to assess their efficacy timely in vivo (in-vivo senescence imaging).

Previous UK SPINE funding enabled us to pre-clinically validate a novel senolytic with a higher efficacy and specificity than first-generation senolytics.  We want to bring our novel senolytic into a clinical environment as safely and effectively as possible, and in the present application, we address the unmet need for a minimally invasive senescence biomarker to facilitate the translation. We aim to generate pre-clinical proof-of-concept that [18F]PyGal PET imaging may be used as biomarker of senescent cell load in clinically relevant settings.If the outcome of this project is successful, we anticipate the translation of [18F]PyGal PET imaging of senescence load into clinical settings such as diagnosis of pathologic conditions associated with senescent cells, monitoring the effects of radiotherapies, and assessment of the efficacy of senolytics.