An octadentate chelator based on 3,4-hydroxypyridinones for 89Zr4+ and 213Bi3+ chelation

The successful application of radiometals for diagnosis and therapy in nuclear medicine requires chelators that efficiently and stably complex the radiometal at low chelator concentration, preferably under mild reaction conditions. We aim to develop new chelators for the radiometals 89Zr and 213Bi. 89Zr (beta+, t1/2 78 h), has utility in PET imaging of antibodies, which require 2 - 5 days post-injection to localize at target tissue prior to imaging. The hexadentate tris(hydroxamate), desferrioxamine-B can coordinate 89Zr4+, but there is some evidence of in vivo instability. The radiotherapeutic alpha-emitting metal, 213Bi (t1/2 45 min) has demonstrated clinical efficacy, but the currently used chelator, DOTA, requires heating at high temperatures to incorporate 213Bi. Based on our previous experience of hexadentate tris(hydroxypyridinone) chelators that demonstrate high affinity for oxophilic metal ions, we aimed to develop an octadentate tetrakis(hydroxypyridinone) ligand containing four 3,4-hydroxypyridinone groups, and evaluate its ability to coordinate 89Zr4+ and 213Bi3+ under mild reaction conditions.

CUSNIR Ruslan;  FOLEY Calum A;  LANGE Jaclyn L;  IMBERTI Cinzia;  MORGENSTERN Alfred;  BRUCHERTSEIFER Frank;  BLOWER Phil;  MA Michelle; 

2017-07-07

SOC NUCLEAR MEDICINE INC

JRC105539

0161-5505,   

http://jnm.snmjournals.org/content/58/supplement_1/889.abstract,    https://publications.jrc.ec.europa.eu/repository/handle/JRC105539,