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Design, Synthesis, And Evaluation Of Novel Protease-Activated Receptor 2 (Par2)-Targeting Imaging Agents For Cancer, Jordan C. Lesarge

Electronic Thesis and Dissertation Repository

Aberrant function and over-expression of protease-activated receptor 2 (PAR2), a GPCR, is associated with various cancers and inflammatory diseases. PAR2-targeting ligands have been developed with therapeutic applications but the development of imaging probes is lacking. A series of PAR2-targeted fluorescent and ¹⁸F-PET imaging agents were synthesized and assessed for PAR2-binding. A novel dye-conjugated peptide, Isox-Cha-Chg-ARK(Sulfo-Cy5)-NH₂ (EC₅₀=16nM, K_D=38nM), showed >10-fold increase in potency and binding affinity for PAR2 compared to the leading known fluorescent probe. A novel PET imaging ¹⁸F-labeled peptide, Isox-Cha-Chg-AR-Dpr([¹⁸F]4-FB)-NH₂, is the first PAR2-targeted in vivo imaging agent. …