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Meeting ReportRadiopharmaceutical Chemistry: New Radiopharmaceuticals

Imaging regulable expression of matriptase in a mouse model for human breast cancer with PET

Julia Choi, Sven Hausner, M. Karen Gagnon, David Kukis, Chen-Yong Lin, Michael Johnson and Julie Sutcliffe
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1927;
Julia Choi
1UC Davis, Dept of Biomedical Engineering, Davis, CA
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Sven Hausner
1UC Davis, Dept of Biomedical Engineering, Davis, CA
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M. Karen Gagnon
1UC Davis, Dept of Biomedical Engineering, Davis, CA
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David Kukis
2UC Davis, Ctr for Molecular and Genomic Imaging, Davis, CA
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Chen-Yong Lin
3Univ of Maryland, School of Medicine, Baltimore, MD
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Michael Johnson
4Georgetown Univ, Dept of Oncology, Lombardi Comprehensive Cancer Ctr, Washington, DC
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Julie Sutcliffe
1UC Davis, Dept of Biomedical Engineering, Davis, CA
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Abstract

1927

Objectives The serine protease matriptase has been implicated in many epithelial cancers. We propose to develop radioimmunoconjugates to image in vivo expression of both the activated and total states of matriptase.

Methods The radioimmunoconjugates 64Cu-TETA-M69 (activated) and 64Cu-TETA-M32 (total matriptase) were synthesized and evaluated in vivo. Briefly, female nude mice were implanted with a tetracycline (dox)-regulable cell line (3E6 cells), and fed dox chow for matriptase-positive expressing tumors or standard chow for control tumors. Mice were injected with 64Cu-TETA-M69 or 64Cu-TETA-M32 (50-150 µCi, 20 µg) and imaged using microPET at 24, 48, 72 and 96h; corresponding biodistribution studies were also performed.

Results 64Cu-labeled immunoconjugates were >95% radiochemically pure and immunoreactive. PET images showed specific accumulation of both immunoconjugates in target positive tumors. Biodistribution revealed a two-fold increase in tumor activity from dox-fed mice over those fed normal chow for 64Cu-TETA-M32 at 96h, with a more modest uptake for 64Cu-TETA-M69.

Conclusions We have demonstrated that tet-regulable matriptase expression can be monitored in vivo using PET. While faster tumor targeting was observed for the total state, activated matriptase is the more relevant target for future clinical development. We observed an upward trend of specific tumor uptake at 96h; longer-lived isotopes may be required for improved detection of activated matriptase.

Research Support Julia C. Choi is supported by the Department of Defense Breast Cancer Research Program under award number W81XWH-08-BCRP.

  • © 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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Imaging regulable expression of matriptase in a mouse model for human breast cancer with PET
Julia Choi, Sven Hausner, M. Karen Gagnon, David Kukis, Chen-Yong Lin, Michael Johnson, Julie Sutcliffe
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1927;

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Imaging regulable expression of matriptase in a mouse model for human breast cancer with PET
Julia Choi, Sven Hausner, M. Karen Gagnon, David Kukis, Chen-Yong Lin, Michael Johnson, Julie Sutcliffe
Journal of Nuclear Medicine May 2009, 50 (supplement 2) 1927;
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