TY - JOUR
T1 - Labeling and in vivo evaluation of novel copper(II) dioxotetraazamacrocyclic complexes
AU - Cutler, Cathy S.
AU - Wuest, Melinda
AU - Anderson, Carolyn J.
AU - Reichert, David E.
AU - Sun, Yizhen
AU - Martell, Arthur E.
AU - Wekh, Michael J.
N1 - Funding Information:
The authors would like to thank Todd A. Perkins and Dr. Deborah W. McCarthy for production of 64 Cu and Margaret M. Morris and Elizabeth L. C. Sherman for their excellent technical assistance. This work was supported by NIH grant CA 42925 (to M.J.W. and A.E.M.) and NIH grant CA 64475 (to C.J.A.).
PY - 2000
Y1 - 2000
N2 - Cu shows promise as both a positron emission tomography imaging and radiotherapeutic radionuclide due to its half-life (T1/2 = 12.7 h), decay characteristics (β+ [19%]; β- [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), l,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 to currently used macrocyclic bifunctional chelators.
AB - Cu shows promise as both a positron emission tomography imaging and radiotherapeutic radionuclide due to its half-life (T1/2 = 12.7 h), decay characteristics (β+ [19%]; β- [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), l,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 to currently used macrocyclic bifunctional chelators.
KW - Biodistribution
KW - Copper-64
KW - Macrocycle
UR - http://www.scopus.com/inward/record.url?scp=0034184839&partnerID=8YFLogxK
U2 - 10.1016/S0969-8051(00)00101-3
DO - 10.1016/S0969-8051(00)00101-3
M3 - Article
C2 - 10938473
AN - SCOPUS:0034184839
SN - 0969-8051
VL - 27
SP - 375
EP - 380
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 4
ER -