Journal article
Polyazamacrocycle Ligands Facilitate Zr-89 Radiochemistry and Yield Zr-89 Complexes with Remarkable Stability
Inorganic chemistry, Vol.59(23), pp.17473-17487
12/07/2020
DOI: 10.1021/acs.inorgchem.0c02722
PMCID: PMC8300002
PMID: 33169605
Abstract
Over the last three decades, the chemistry of zirconium has facilitated antibody development and the clinical management of disease in the precision medicine era. Scientists have harnessed its reactivity, coordination chemistry, and nuclear chemistry to develop antibody-based radiopharmaceuticals incorporating zirconium-89 (Zr-89: t(1/2) = 78.4 h, 22.8%, beta(+): 22.8%, E beta+max = 901 keV; EC: 77%, E-gamma = 909 keV) to improve disease detection, identify patients for individualized therapeutic interventions. and monitor their response to those interventions. However, release of the Zr-89(4+) ion from the radiopharmaceutical remains a concern, since it may confound the interpretation of clinical imaging data, negatively affect dosimetric calculations, and hinder treatment planning. In this report, we relate our novel observations involving the use of polyazamacrocycles as zirconium-89 chelators. We describe the synthesis and complete characterization of zirconium 2,2',2 '',2'"- (1,4,7,10-tetraazacyclotridecane- 1,4,7,10-tetrayl) tetraacetic acid Zr-TRITA, zirconium 3,6,9,15-Tetraazabicyclo [9.3.1] pentacleca-1(15), 11, 13-triene-3,6,9-triacetic acid (Zr-PCTA), and zirconium 2,2',2 ''- (1,4,7-triazacyclononane-1,4,7-triyl) triacetic acid (Zr-NOTA). In addition, we elucidate the solid-state structure of each complex using single-crystal X-ray diffraction analysis. Finally, we found that [Zr-89]Zr-PCTA and [Zr-89]Zr-NOTA demonstrate excellent stability in vitro and in vivo and provide a rationale for these observations. These innovative findings have the potential to guide the development of safer and more robust immuno-PET agents to improve precision medicine applications.
Details
- Title: Subtitle
- Polyazamacrocycle Ligands Facilitate Zr-89 Radiochemistry and Yield Zr-89 Complexes with Remarkable Stability
- Creators
- Darpan N. Pandya - University of IowaKelly E. Henry - Memorial Sloan Kettering Cancer CenterCynthia S. Day - Wake Forest UniversityStephen A. Graves - University of IowaVeronica L. Nagle - Memorial Sloan Kettering Cancer CenterThomas R. Dilling - Memorial Sloan Kettering Cancer CenterAkesh Sinha - University of IowaBrandie M. Ehrmann - University of North Carolina at Chapel HillNikunj B. Bhatt - Columbia UniversityYusuf Menda - University of IowaJason S. Lewis - Memorial Sloan Kettering Cancer CenterThaddeus J. Wadas - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Inorganic chemistry, Vol.59(23), pp.17473-17487
- DOI
- 10.1021/acs.inorgchem.0c02722
- PMID
- 33169605
- PMCID
- PMC8300002
- NLM abbreviation
- Inorg Chem
- ISSN
- 0020-1669
- eISSN
- 1520-510X
- Publisher
- Amer Chemical Soc
- Number of pages
- 15
- Grant note
- Wake Forest Innovations University of Iowa Center for Molecular Imaging and Nanotechnology (CMINT) Tow Fellowship through MSK CHE-0234489 / National Science Foundation; National Science Foundation (NSF) P30 CA08748 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Wake Forest University Health Sciences 2016-BIG-6524 / North Carolina Biotechnology Center
- Language
- English
- Date published
- 12/07/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Radiation Oncology
- Record Identifier
- 9984313075302771
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