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Title: Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89

The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. We report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. And while both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. The differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.
Authors:
 [1] ;  [1] ;  [2] ;  [2] ;  [2] ; ORCiD logo [1] ;  [3]
  1. Wake Forest School of Medicine, Winston-Salem, NC (United States). Dept. of Cancer Biology
  2. Lumiphore, Inc., Berkeley, CA (United States)
  3. Genentech Inc., San Francisco, CA (United States)
Publication Date:
Grant/Contract Number:
SC0008657
Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 12; Journal Issue: 6; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Research Org:
Washington Univ., St. Louis, MO (United States)
Sponsoring Org:
USDOE Office of Science (SC), Nuclear Physics Isotope Program (NP) (SC-26)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE
OSTI Identifier:
1374895

Bhatt, Nikunj B., Pandya, Darpan N., Xu, Jide, Tatum, David, Magda, Darren, Wadas, Thaddeus J., and Boswell, C. Andrew. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89. United States: N. p., Web. doi:10.1371/journal.pone.0178767.
Bhatt, Nikunj B., Pandya, Darpan N., Xu, Jide, Tatum, David, Magda, Darren, Wadas, Thaddeus J., & Boswell, C. Andrew. Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89. United States. doi:10.1371/journal.pone.0178767.
Bhatt, Nikunj B., Pandya, Darpan N., Xu, Jide, Tatum, David, Magda, Darren, Wadas, Thaddeus J., and Boswell, C. Andrew. 2017. "Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89". United States. doi:10.1371/journal.pone.0178767. https://www.osti.gov/servlets/purl/1374895.
@article{osti_1374895,
title = {Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89},
author = {Bhatt, Nikunj B. and Pandya, Darpan N. and Xu, Jide and Tatum, David and Magda, Darren and Wadas, Thaddeus J. and Boswell, C. Andrew},
abstractNote = {The development of bifunctional chelators (BFCs) for zirconium-89 immuno-PET applications is an area of active research. We report the synthesis and evaluation of octadentate hydroxyisophthalamide ligands (1 and 2) as zirconium-89 chelators. And while both radiometal complexes could be prepared quantitatively and with excellent specific activity, preparation of 89Zr-1 required elevated temperature and an increased reaction time. 89Zr-1 was more stable than 89Zr-2 when challenged in vitro by excess DTPA or serum proteins and in vivo during acute biodistribution studies. The differences in radiometal complex stability arise from structural changes between the two ligand systems, and suggest further ligand optimization is necessary to enhance 89Zr chelation.},
doi = {10.1371/journal.pone.0178767},
journal = {PLoS ONE},
number = 6,
volume = 12,
place = {United States},
year = {2017},
month = {6}
}

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