Development of a New Class of CXCR4-Targeting Radioligands Based on the Endogenous Antagonist EPI-X4 for Oncological Applications.

ABSTRACT: The peptide fragment of human serum albumin that was identified as an inhibitor of C-X-C motif chemokine receptor 4 (CXCR4), termed EPI-X4, was investigated as a scaffold for the development of CXCR4-targeting radio-theragnostics. Derivatives of its truncated version JM#21 (ILRWSRKLPCVS) were conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and tested in Jurkat and Ghost-CXCR4 cells. Ligand-1, -2, -5, -6, -7, -8, and -9 were selected for radiolabeling. Molecular modeling indicated that ¹⁷⁷Lu-DOTA incorporation C-terminally did not interfere with the CXCR4 binding. Lipophilicity, in vitro plasma stability, and cellular uptake hinted ¹⁷⁷Lu-7 as superior. In Jurkat xenografts, all

SUBMITTER: Gaonkar RH 

PROVIDER: S-EPMC10350915 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature