Labeling and in Vivo Evaluation of Novel Copper(II) Dioxotetraazamacrocyclic Complexes

ABSTRACT. 64Cu shows promise as both a positron emission tomography imaging and radiotherapeutic radionuclide due to its half-life (T1/2 5 12.7 h), decay characteristics (b 1 [19%]; b2 [40%]), and the capability to produce it on a large-scale with high specific activity on a biomedical cyclotron. Macrocyclic chelators are generally used as bifunctional chelators to attach Cu(II) to antibodies and peptides due to their relatively high in vitro stability. To investigate neutral Cu(II) complexes, we performed labeling experiments with six tetraazamacrocyclic ligands with different chelate ring sizes. 1,4,8,11-Tetraazacyclotetradecane-3,9-dione (1), 1,4,8,11-tetraazacyclotetradecane-5,7-dione (2), 1,4,7,10-tetraazacyclotridecane-11,13-dione (3), 1,4,7,10-tetraazacyclotridecane-2,9-dione (4), 1,4,7,10-tetraazacyclododecane-2,9-dione (5), and 1,4,7,10-tetraazacyclotridecane-3,8-dione (6) were radiolabeled with 64Cu. Only 64Cu-labeled 1 readily formed a complex in high purity, and therefore was evaluated in vivo. The rapid blood, liver, and kidney clearance of 64Cu-labeled 1 suggest that ligand 1 may be useful as a macrocyclic structure to design new bifunctional chelators for copper radionuclides in diagnostic or radiotherapeutic studies and is a potential alternative t