Abstract A227: Positron emission tomographic (PET) imaging of activated matriptase, a marker for cancer progression

The serine protease matriptase has been implicated in epithelial cancers, has been found in ∼45% of node‐negative breast cancers at high levels, and is indicated as a biomarker for survival independent of HER‐2/ neu . While in vitro methods are invaluable, few breast cancer cell‐lines express matriptase, though 83% of breast cancer patients are positive for matriptase—this suggests that imaging the in vivo behavior of matriptase may aid in understanding its role in the context of the tumor system. Specifically, activated matriptase is associated with cancer progression. We have developed radiotracers against activated matriptase for in vivo imaging using PET. M69, an antibody against activated matriptase, was functionalized to capture [ 64 Cu]copper or [ 89 Zr]zirconium: 64 Cu‐TETA‐M69 and 89 Zr‐DF‐M69 were evaluated in a mouse model of human breast cancer. A dox‐regulable pair of PyVmT cell‐lines was bilaterally introduced into nude female mice to generate matriptase‐positive and control tumors. Mice were fed dox chow ad libitum , administered radiotracer, imaged using microPET at 1–4d p.i.; and through 336h for 89 Zr; corresponding biodistribution was performed. PET images indicated specific tumor retention. Biodistribution at 4d revealed both 64 Cu‐TETA‐M69 and 89 Zr‐DF‐M69 retained two‐fold uptake ratios for the positive tumor over control; this was also observed at 336h for 89 Zr‐DF‐M69. Immunohistochemistry on FFPE tissues confirmed human matriptase expression in the positive tumor. In summary, we have developed two novel radiotracers and performed the first in vivo imaging of activated matriptase. This approach has the potential for imaging metastasis, the primary cause of mortality in breast cancer patients. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A227.