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

• Applicant: Professor Dr. Jan Münch
• Subject Area: Pharmacy ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441271438

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, an endogenous antagonist and inverse agonist of CXCR4, termed EPI-X4, has been identified by the applicants. EPI-X4 is a 16-mer peptide derived from human serum albumin that specifically binds CXCR4 but no other G-protein coupled receptors (GPCRs). 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. Radio-theranostics 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.

• DFG Programme: Research Grants
• International Connection: Switzerland
• Cooperation Partner: Professorin Dr. Melpomeni Fani