New Tris(hydroxypyridinone) Bifunctional Chelators Containing Isothiocyanate Groups Provide a Versatile Platform for Rapid One-Step Labeling and PET Imaging with (68)Ga(3.)
- Bioconjug Chem. 2016 Feb 17;27(2):309-18. doi: 10.1021/acs.bioconjchem.5b00335.
- 1. King's College London , Division of Imaging Sciences and Biomedical Engineering, Fourth Floor Lambeth Wing, St Thomas' Hospital, London SE1 7EH, United Kingdom.
- 2. Peter MacCallum Cancer Centre , East Melbourne, Victoria 3002, Australia.
- 3. Sir Peter MacCallum Department of Oncology, University of Melbourne , Parkville, Victoria 3010, Australia.
Two new bifunctional tris(hydroxypyridinone) (THP) chelators designed specifically for rapid labeling with (68)Ga have been synthesized, each with pendant isothiocyanate groups and three 1,6-dimethyl-3-hydroxypyridin-4-one groups. Both compounds have been conjugated with the primary amine group of a cyclic Integrin targeting peptide, RGD. Each conjugate can be radiolabeled and formulated by treatment with generator-produced (68)Ga(3+) in over 95% radiochemical yield under ambient conditions in less than 5 min, with specific activities of 60-80 MBq nmol(-1). Competitive binding assays and in vivo biodistribution in mice bearing U87MG tumors demonstrate that the new (68)Ga(3+)-labeled THP peptide conjugates retain affinity for the αvβ3 Integrin receptor, clear within 1-2 h from circulation, and undergo receptor-mediated tumor uptake in vivo. We conclude that bifunctional THP chelators can be used for simple, efficient labeling of (68)Ga biomolecules under mild conditions suitable for peptides and proteins.