Improving Affinity while Reducing Kidney Uptake of CXCR4-Targeting Radioligands Derived from the Endogenous Antagonist EPI-X4.

The C-X-C chemokine receptor 4 (CXCR4) is highly upregulated in most cancers, making it an ideal target for delivering radiation therapy to tumors. We previously demonstrated the feasibility of targeting CXCR4 in vivo using a radiolabeled derivative of EPI-X4, an endogenous CXCR4 antagonist, named DOTA-K-JM#173. However, this derivative showed undesirable accumulation in the kidneys, which would limit its clinical use.

Modular One-Pot Strategy for the Synthesis of Heterobivalent Tracers.

Bivalent ligands, i.e., molecules having two ligands covalently connected by a linker, have been gathering attention since the first description of their pharmacological potential in the early 80s.