Proof-of-concept of CXCR4 targeting in vivo using radiotracers based on the endogenous antagonist EPI-X4

Targeted imaging of the C-X-C motif chemokine receptor (CXCR4) in several cancer types has been an area of intensive research. The identification of an endogenous peptide antagonist of CXCR4, termed EPI-X4, opens the space for the development of a new class of radiotracers for non-invasive molecular imaging and treatment of these cancers. Rational drug design based on EPI-X4 led to optimized analogs (coded JMF-01 to JMF-07) with increased antagonistic activity. We developed DOTA-conjugated analogs and studied them in vitro labeled with 177Lu and 68Ga (work presented at EANM 2021). We report herein the in vivo feasibility study in CXCR4-expressing tumor xenografts