Abstract
1884
Objectives 64Cu-labeled proteins are being developed as PET imaging agents. However, to attach 64Cu to a protein, a bifunctional chelator (BFC) is required to chelate the 64Cu and form a stable complex, protecting the metal from transchelation to endogenous proteins. The major disadvantage of existing BFCs is loss of 64Cu in vivo, resulting in localization of the free radiometal in the liver, intestines, and kidneys. The objective of this study was to evaluate the stability of two 64Cu complexes that were expected to show very little loss of 64Cu in vivo and thus very low non-target tissue uptake.
Methods The 64Cu complexes of 4,11-diene imine and 4,11-diene amine were synthesized and characterized. 4,11–diene amine is the reduced version of the 4,11-diene imine ligand. The biodistribution of the 64Cu complexes was evaluated in mice using microPET.
Results Despite the fact that the two complexes have the same charge and a very similar structure, the biodistribution of the two complexes is noticeably different: reduction of the imines to form the saturated macrocyclic complex apparently reduces the stability of the 64Cu complex. The 64Cu complex of 4,11-diene imine showed very little uptake in the liver, gut and kidneys and rapid excretion into the bladder whereas the 64Cu complex of 4,11-diene amine showed noticeable uptake in the liver, gut and kidneys and rapid excretion into the bladder by 4 h post-injection.
Conclusions The 64Cu-4,11-diene imine showed significantly lower uptake in the liver, gut, and kidneys than 64Cu-4,11-diene amine suggesting that the imine complex is more stable in vivo. 4,11-diene imine may, therefore, be a promising core for the development of a new class of bifunctional chelators for 64Cu.
Research Support R01CA094338
- © 2009 by Society of Nuclear Medicine