Synthesis, 64 Cu-labeling and PET imaging of 1,4,7-triazacyclononane derived chelators with pendant azaheterocyclic arms

The TACN derived chelators NOTI, NOTI-Me and NOTThia were synthesized in a facile, single reaction step. The new chelators were readily labeled with 64 Cu under mild conditions over a wide pH range. The corresponding 64 Cu complexes are of high stability in vitro as determined by Cu 2+ exchange experiments, acid decomplexation and serum stability studies. Single crystal X-ray analysis showed that the six-coordinate copper complexes exhibited a distorted prismatic CuN 3 N′ 3 coordination geometry similar to Cu(NOTA). Biological testing by small animal PET imaging revealed retention of 64 Cu complexes in the kidneys and, to a lesser extent, in the liver. Altogether, the results presented support the development of bifunctional derivatives for conjugation to targeting vectors and further testing in vivo .