PET imaging of activated matriptase, a marker for cancer progression

Objectives Activated matriptase is a serine protease associated with cancer progression. We propose to develop radioimmunoconjugates against activated matriptase for in vivo imaging using PET.

Methods M69 antibody (against activated matriptase) was functionalized to capture [⁶⁴Cu]copper or [⁸⁹Zr]zirconium: ⁶⁴Cu-TETA-M69 and ⁸⁹Zr-Df-M69 were evaluated in vivo. Briefly, a tet-regulable cell-line (human breast cancer model-derived) was introduced into female nude mice, and fed dox chow (+dox) for matriptase-positive or normal chow (-dox) for control tumors. Mice were imaged with microPET at 24, 48, 72, and 96h; and through 120, 144, 192, and 288h for ⁸⁹Zr; corresponding biodistribution studies were performed.

Results Radioimmunoconjugates were >95% radiochemical purity and immunoreactive. PET images and biodistribution indicated specific tumor retention with the tet-regulable model; however, more liver uptake for ⁸⁹Zr-Df-M69 was observed than for ⁶⁴Cu-TETA-M69. Biodistribution at 96h revealed ⁶⁴Cu-TETA-M69 tumor-to-blood ratios of 2.25 and 2.01; and 2.91 and 1.47 for ⁸⁹Zr-Df-M69, for +dox and -dox, respectively. At 310h, ratios were 9.14 and 5.16 for ⁸⁹Zr-Df-M69.

Conclusions We have developed two radioimmunoconjugates for imaging activated matriptase in vivo. This approach has the potential for imaging metastasis, the primary cause of mortality in breast cancer patients.

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