Development of Bifunctional Chelates Bearing Hydroxamate Arms for Highly Efficient ⁶⁴Cu Radiolabeling

Convenient approaches for the synthesis of DOTHA₂ and NOTHA₂, two cyclic bifunctional chelates (BFCs) bearing hydroxamate arms, have been developed. These novel BFCs coordinate ⁶⁴Cu with fast kinetics at room temperature in a wide range of concentrations and pH. The corresponding radiochemical complexes showed high stability, low residual activity in various tissues, and fast clearance in normal mice. The ability to conjugate DOTHA₂ to both a small peptide and a large protein is also reported.