Sc-HOPO: A Potential Construct for Use in Radioscandium-Based Radiopharmaceuticals

• Published in: Inorganic chemistry Vol. 62; no. 50; pp. 20567 - 20581
• Main Authors: Phipps, Michael D., Cingoranelli, Shelbie, Bhupathiraju, N. V. S. Dinesh K., Younes, Ali, Cao, Minhua, Sanders, Vanessa A., Neary, Michelle C., Devany, Matthew H., Cutler, Cathy S., Lopez, Gustavo E., Saini, Shefali, Parker, Candace C., Fernandez, Solana R., Lewis, Jason S., Lapi, Suzanne E., Francesconi, Lynn C., Deri, Melissa A.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.12.2023; American Chemical Society (ACS)
• Subjects: Animals; Chelating Agents - chemistry; Chemistry; Ligands; Mice; Positron-Emission Tomography - methods; Pyridones - chemistry; Radiopharmaceuticals - chemistry
• ISSN: 0020-1669; 1520-510X; 1520-510X
• DOI: 10.1021/acs.inorgchem.2c03931

Three isotopes of scandium43Sc, 44Sc, and 47Schave attracted increasing attention as potential candidates for use in imaging and therapy, respectively, as well as for possible theranostic use as an elementally matched pair. Here, we present the octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO), an effective chelator for hard cations, as a potential ligand for use in radioscandium constructs with simple radiolabeling under mild conditions. HOPO forms a 1:1 Sc-HOPO complex that was fully characterized, both experimentally and theoretically. [47Sc]­Sc-HOPO exhibited good stability in chemical and biological challenges over 7 days. In healthy mice, [43,47Sc]­Sc-HOPO cleared the body rapidly with no signs of demetalation. HOPO is a strong candidate for use in radioscandium-based radiopharmaceuticals.