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Meeting ReportRadiopharmaceutical Chemistry: New Radiopharmaceuticals

Evaluating bifuctional chelates for antibody imaging with Cu-64

Cara Ferreira, Donald Yapp, Sarah Crisp, Brent Sutherland, Martin Gleave, Corrine Bensimon, Paul Jurek and Garry Kiefer
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 373;
Cara Ferreira
1MDS Nordion, Vancouver, BC, Canada
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Donald Yapp
2British Columbia Cancer Agency, Vancouver, BC, Canada
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Sarah Crisp
1MDS Nordion, Vancouver, BC, Canada
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Brent Sutherland
2British Columbia Cancer Agency, Vancouver, BC, Canada
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Martin Gleave
2British Columbia Cancer Agency, Vancouver, BC, Canada
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Corrine Bensimon
1MDS Nordion, Vancouver, BC, Canada
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Paul Jurek
3Macrocyclics Inc., Dallas, TX
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Garry Kiefer
3Macrocyclics Inc., Dallas, TX
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Abstract

373

Objectives Cu-64 has potential utility in the radiolabeling of antibodies (mAbs) for both PET imaging and radiotherapy. Improved bifunctional chelates (BFCs) are needed to facilitate efficient radiolabeling of mAbs under mild conditions and to yield stable, target specific agents. Two novel BFCs, Oxo and PCTA, were compared to DOTA for use in mAb imaging with Cu-64.

Methods Each of the BFCs was conjugated to trastuzumab, a mAb that targets the HER-2/neu receptor. The radiolabeling of the conjugates was optimized. Receptor binding was analyzed in 4 cell lines, using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER-2/neu positive or negative tumors.

Results Both the Oxo and PCTA conjugates incorporated Cu-64 faster and in higher radiochemical yields than the DOTA conjugate. Specific activities up to 17,000Ci/mmol were achievable. Flow cytometry established that the conjugates retained the immunoreactivity of the native mAb. Radioassays confirmed target specificity; Cu-64 radiolabeled conjugates bound to HER-2/neu expressing cells, but not non-expressing cells. The binding could be blocked by excess mAb. From the in vivo studies, comparison of the HER-2/neu positive tumors and the negative control tumors showed that the Oxo and PCTA conjugates had greater target specificity than the DOTA conjugate. The tumor-to-background ratios were applicable to imaging at 24 h.

Conclusions The mAb conjugates of PCTA and Oxo were shown to be superior to the DOTA conjugate with respect to radiolabeling efficiency and target specificity in vivo.

  • © 2009 by Society of Nuclear Medicine
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Journal of Nuclear Medicine
Vol. 50, Issue supplement 2
May 2009
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Evaluating bifuctional chelates for antibody imaging with Cu-64
Cara Ferreira, Donald Yapp, Sarah Crisp, Brent Sutherland, Martin Gleave, Corrine Bensimon, Paul Jurek, Garry Kiefer
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 373;

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Evaluating bifuctional chelates for antibody imaging with Cu-64
Cara Ferreira, Donald Yapp, Sarah Crisp, Brent Sutherland, Martin Gleave, Corrine Bensimon, Paul Jurek, Garry Kiefer
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 373;
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