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Updated: Mar 15, 2026

The Bioconjugation and Radiosynthesis of 89Zr-DFO-labeled Antibodies
Published on: February 12, 2015
Macrocycle-Based Hydroxamate Ligands for Complexation and Immunoconjugation of 89Zirconium for Positron Emission
Eszter Boros1, Jason P Holland2, Nathaniel Kenton1
1The Athinoula A. Martinos Center for Biomedical Imaging Department of Radiology, Massachusetts General Hospital Harvard Medical School, 149 Thirteenth Street, Suite 2301 Charlestown, MA 02129 (USA).
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.
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