Design, synthesis, and evaluation of a novel PET imaging agent targeting lipofuscin in senescent cells

Abstract

Promoting a senescent phenotype to suppress tumour progression may present an alternative strategy for treating cancer and encourages the development of positron emission tomography (PET) imaging biomarkers for assessing response to treatment. The accumulation of lipofuscin deposits in senescent cells is visualised using the pathology stain Sudan Black B (SBB) which is an emerging biomarker of senescence. We describe the design, synthesis and evaluation of [¹⁸F]fluoroethyltriazole-SBB ([¹⁸F]FET-SBB), a fluorine-18 radiolabelled derivative of SBB. The in vitro uptake of [¹⁸F]FET-SBB in a senescent cell line corelated with lipofuscin deposits; in vivo PET imaging and metabolite analysis confirm a favourable pharmacokinetic and metabolic profile for further studies of in vivo models of senescence.