Novel Bifunctional Chelators for Use in Tumor Targeting

• Applicant: Dr. Ata Makarem, Ph.D.
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546563412

Bifunctional chelators play a crucial role in radiopharmaceutical syntheses and tumor imaging by labeling bioactive molecules with theranostic metal isotopes (radiometals). In recent years, HBED-type chelators have gained significant attention for their application in nuclear medicine. HBED is a hexadentate aminocarboxyphenol-based chelator with an N2O4 donor set, exhibiting strong binding to small and "hard" metal ions, especially gallium(III) isotopes. Its bifunctional variants, such as HBED-CC, incorporate additional functional groups for covalent conjugation to bioactive targeting molecules, facilitating the delivery of radioactive payloads to tumor cells in patients. Despite the advantages of HBED - especially the ability of rapid chelation/radiolabeling at ambient temperature - its applications in radiopharmaceutical chemistry and nuclear medicine are almost limited to gallium-based agents. To solve this problem, we introduce several chelator scaffolds based on HBED and aim to investigate them from various chemical and biochemical aspects, focusing on non-radioactive techniques. This includes complex chemistry, (bio)conjugation behavior, and in-vitro activity using validated ICP-MS cell assays. Besides this, some basic radioactive tests will be conducted collaboratively, as a proof-of-principle. In summary, this is a fundamental research project involving 70-80% chemistry and 20-30% molecular biology.

• DFG Programme: Research Grants
• International Connection: United Kingdom
• Co-Investigator: Professor Dr. Wolfgang Maison, Ph.D.
• Cooperation Partners: Professorin Gabriela Kramer-Marek; Professorin Gabriela Kramer-Marek