PT  - JOURNAL ARTICLE
AU  - Julia Choi
AU  - Sven Hausner
AU  - M. Karen Gagnon
AU  - David Kukis
AU  - Chen-Yong Lin
AU  - Michael Johnson
AU  - Julie Sutcliffe
TI  - Imaging regulable expression of matriptase in a mouse model for human breast cancer with PET
DP  - 2009 May 01
TA  - Journal of Nuclear Medicine
PG  - 1927--1927
VI  - 50
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/50/supplement_2/1927.short
4100  - http://jnm.snmjournals.org/content/50/supplement_2/1927.full
SO  - J Nucl Med2009 May 01; 50
AB  - 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.