CXCR4-targeted radio-theragnostics based on the endogenous ligand EPI-X4 for oncological applications

CXCR4-targeted imaging has been an area of intensive research due to the overexpression of CXCR4 in several cancer types. We utilized the Endogenous Peptide Inhibitor of CXCR4 (EPI-X4), a human serum albumin fragment (1), as scaffold for developing novel CXCR4-targeting radioligands. We identified ⁶⁸Ga-/¹⁷⁷Lu-JMF-04 (dILRWSRKK(⁶⁸Ga-/¹⁷⁷Lu-DOTA)-NH₂) as the derivative able to visualize CXCR4-expressing tumors, however, it had undesirably high kidney uptake. In a follow-up structure optimization study, we developed two optimized derivatives, JMF-10 and JMF-11, presented herein.