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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 11/2010

01-11-2010 | Original Article

Comparison of bifunctional chelates for 64Cu antibody imaging

Authors: Cara L. Ferreira, Donald T. T. Yapp, Sarah Crisp, Brent W. Sutherland, Sylvia S. W. Ng, Martin Gleave, Corinne Bensimon, Paul Jurek, Garry E. Kiefer

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2010

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Abstract

Purpose

Improved bifunctional chelates (BFCs) are needed to facilitate efficient 64Cu radiolabeling of monoclonal antibodies (mAbs) under mild conditions and to yield stable, target-specific agents. The utility of two novel BFCs, 1-Oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA), for mAb imaging with 64Cu were compared to the commonly used S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA).

Methods

The BFCs were conjugated to trastuzumab, which targets the HER2/neu receptor. 64Cu radiolabeling of the conjugates was optimized. Receptor binding was analyzed using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER2/neu-positive or HER2/neu-negative tumors.

Results

64Cu-Oxo-DO3A- and PCTA-trastuzumab were prepared at room temperature in >95% radiochemical yield (RCY) in <30 min, compared to only 88% RCY after 2 h for the preparation of 64Cu-DOTA-trastuzumab under the same conditions. Cell studies confirmed that the immunoreactivity of the mAb was retained for each of the bioconjugates. In vivo studies showed that 64Cu-Oxo-DO3A- and PCTA-trastuzumab had higher uptake than the 64Cu-DOTA-trastuzumab at 24 h in HER2/neu-positive tumors, resulting in higher tumor to background ratios and better tumor images. By 40 h all three of the 64Cu-BFC-trastuzumab conjugates allowed for clear visualization of the HER2/neu-positive tumors but not the negative control tumor.

Conclusion

The antibody conjugates of PCTA and Oxo-DO3A were shown to have superior 64Cu radiolabeling efficiency and stability compared to the analogous DOTA conjugate. In addition, 64Cu-PCTA and Oxo-DO3A antibody conjugates may facilitate earlier imaging with greater target to background ratios than the analogous 64Cu-DOTA antibody conjugates.
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Metadata
Title
Comparison of bifunctional chelates for 64Cu antibody imaging
Authors
Cara L. Ferreira
Donald T. T. Yapp
Sarah Crisp
Brent W. Sutherland
Sylvia S. W. Ng
Martin Gleave
Corinne Bensimon
Paul Jurek
Garry E. Kiefer
Publication date
01-11-2010
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2010
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-010-1506-1

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