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

Brickute, Diana; Chen, Cen; Braga, Marta; Barnes, Chris; Wang, Ning; Allott, Louis; Aboagye, Eric O.

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.

Citation

Brickute, D., Chen, C., Braga, M., Barnes, C., Wang, N., Allott, L., & Aboagye, E. O. (2022). Design, synthesis, and evaluation of a novel PET imaging agent targeting lipofuscin in senescent cells. RSC advances, 12(40), 26372-26381. https://doi.org/10.1039/d2ra04535d

• Journal Article Type: Article
• Acceptance Date: Sep 6, 2022
• Online Publication Date: Sep 15, 2022
• Publication Date: 2022
• Deposit Date: Oct 15, 2022
• Publicly Available Date: Oct 17, 2022
• Journal: RSC Advances
• Print ISSN: 2046-2069
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 40
• Pages: 26372-26381
• DOI: https://doi.org/10.1039/d2ra04535d
• Keywords: General Chemical Engineering; General Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4095209