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

Abstract

The TACN derived chelators NOTI, NOTI-Me and NOTThia were synthesized in a facile, single reaction step. The new chelators were readily labeled with ⁶⁴Cu under mild conditions over a wide pH range. The corresponding ⁶⁴Cu complexes are of high stability in vitro as determined by Cu²⁺ exchange experiments, acid decomplexation and serum stability studies. Single crystal X-ray analysis showed that the six-coordinate copper complexes exhibited a distorted prismatic CuN₃N′₃ coordination geometry similar to Cu(NOTA). Biological testing by small animal PET imaging revealed retention of ⁶⁴Cu 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.