Development of a new class of radiopharmaceuticals for diagnosis and therapy of CXCR4-expressing malignancies based on the endogenous CXCR4 antagonist EPI-X4

The pathological overexpression of the C-X-C motif chemokine receptor 4 (CXCR4) in more than 23 human cancers designate CXCR4 as a “wide spectrum” molecular target in oncology. In nuclear medicine, radiolabeled molecules can specifically target such cell surface receptors and can be designed for blending diagnostic and therapeutic properties within the same molecule (radio-theranostics). Recently, the applicants have identified an endogenous antagonist of CXCR4, termed EPI-X 4. EPI-X4 is  a 16-mer peptide derived from human serum albumin that specifically binds CXCR4 but no other G-protein coupled receptors, without causing receptor activation. Several synthetic derivatives of EPI-X4 with increased affinity for CXCR4, resistance against proteolytic degradation in blood and high systemic retention times have been developed. Radiotheranostics based on EPI-X4 may thus offer new imaging tests and therapeutic options to patients suffering from CXCR4-expressing malignancies. The proposed research project would be the first study aiming to evaluate a new class of radiopharmaceuticals based on an endogenous peptide naturally present in the human body, which may have less off-target effects as compared to small molecules.