Evaluation of a 3-hydroxypyridin-2-one (2,3-HOPO) based macrocyclic chelator for 89Zr4+ and its use for immunoPET imaging of HER2 positive model of ovarian carcinoma in mice

Jeff N. Tinianow, Darpan N. Pandya, Sylvie L. Pailloux, Annie Ogasawara, Alexander N. Vanderbilt, Herman S. Gill, Simon P. Williams, Thaddeus J. Wadas, Darren Magda, Jan Marik

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37 Scopus citations


A novel octadentate 3-hydroxypyridin-2-one (2,3-HOPO) based di-macrocyclic ligand was evaluated for chelation of 89Zr; subsequently, it was used as a bi-functional chelator for preparation of 89Zr-labeled antibodies. Quantitative chelation of 89Zr4++ with the octadentate ligand forming 89ZrL complex was achieved under mild conditions within 15 minutes. The 89Zr-complex was stable in vitro in presence of DTPA, but a slow degradation was observed in serum. In vivo, the hydrophilic 89Zr-complex showed prevalently renal excretion; and an elevated bone uptake of radioactivity suggested a partial release of 89Zr4++ from the complex. The 2,3-HOPO based ligand was conjugated to the monoclonal antibodies, HER2-specific trastuzumab and an isotypic anti-gD antibody, using a p-phenylene bis-isothiocyanate linker to yield products with an average loading of less than 2 chelates per antibody. Conjugated antibodies were labeled with 89Zr under mild conditions providing the PET tracers in 60-69% yield. Despite the limited stability in mouse serum; the PET tracers performed very well in vivo. The PET imaging in mouse model of HER2 positive ovarian carcinoma showed tumor uptake of 89Zr-trastuzumab (29.2 ± 12.9 %ID/g) indistinguishable (p = 0.488) from the uptake of positive control 89Zr-DFO-trastuzumab (26.1 ± 3.3 %ID/g). In conclusion, the newly developed 3-hydroxypyridin-2-one based di-macrocyclic chelator provides a viable alternative to DFO-based heterobifunctional ligands for preparation of 89Zr-labeled monoclonal antibodies for immunoPET studies.

Original languageEnglish (US)
Pages (from-to)511-521
Number of pages11
Issue number4
StatePublished - 2016

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© Ivyspring International Publisher.


  • 2,3-HOPO
  • 3-hydroxypyridin-2-one
  • Imaging
  • ImmunoPET
  • Monoclonal antibody
  • Positron emission tomography
  • Radiolabeling
  • Zr


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