We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Macrocycle-Based Hydroxamate Ligands for Complexation and Immunoconjugation of <sup>89</sup>Zirconium for Positron Emission Tomography (PET) Imaging.
- Authors
Boros, Eszter; Holland, Jason P.; Kenton, Nathaniel; Rotile, Nicholas; Caravan, Peter
- Abstract
Four novel chelators ( L1- L4) and their 89zirconium complexes were prepared and compared with the 89zirconium desferrioxamine B (DFO) complex. The new chelates are based on 1,4,7,10-tetraazacyclododecane (cyclen) and 1,4,8,11-tetraazacyclotetradecane (cyclam) scaffolds and present either three or four hydroxamate arms for coordination with Zr4+ ions with coordination numbers between six and eight. The 89Zr- L4 complex showed similar stability to that of 89Zr-DFO when incubated in either rat blood plasma or ethylenediaminetetraacetic acid challenge experiments. Positron imaging and biodistribution studies in mice showed that 89Zr- L4 had similar pharmacokinetic behavior to that of 89Zr-DFO, with rapid renal elimination and low residual activity in background tissues. A bifunctional version of L4 ( L5) was synthesized and conjugated to trastuzumab; an anti-HER2/neu antibody. Immunopositron emission tomography imaging and biodistribution with 89Zr- L5-trastuzumab revealed high tumor to background ratios (tumor/blood ratio: 14.2±2.25) and a high tumor specificity that was comparable to the performance of 89Zr-DFO-trastuzumab.
- Subjects
MACROCYCLIC compound synthesis; LIGANDS (Chemistry); ZIRCONIUM compounds synthesis; DEFEROXAMINE; POSITRON emission tomography; COMPLEXATION reactions
- Publication
ChemPlusChem, 2016, Vol 81, Issue 3, p274
- ISSN
2192-6506
- Publication type
Article
- DOI
10.1002/cplu.201600003