PT  - JOURNAL ARTICLE
AU  - LeBeau, Aaron
AU  - Vanbrocklin, Henry
AU  - Craik, Charles
TI  - Imaging active matriptase in cancer using site-specific recombinant human antibodies
DP  - 2012 May 01
TA  - Journal of Nuclear Medicine
PG  - 1654--1654
VI  - 53
IP  - supplement 1
4099  - http://jnm.snmjournals.org/content/53/supplement_1/1654.short
4100  - http://jnm.snmjournals.org/content/53/supplement_1/1654.full
SO  - J Nucl Med2012 May 01; 53
AB  - 1654 Objectives Cancer-associated proteases represent candidate biomarkers that can be leveraged for diagnostic/prognostic purposes. One candidate for adenocarcinomas is the membrane bound serine protease matriptase. The purpose of this research is to characterize matriptase activity in vivo and in vitro in different cancer models using inhibitory antibodies specific for active matriptase. Methods Full length IgG antibodies for active matriptase were labeled with AlexaFluor 680 and 111In for NIR and SPECT imaging. The initial NIR study was performed on eight different cancer xenografts while the SPECT study used three xenografts, including a patient-derived xenograft (PDX) originating from metastatic colon cancer. AlexaFluor 488 labeled antibodies were used to detect active matriptase in live-cell imaging and in tissue microarrays. Results Out of the eight xenografts studied in the NIR experiment, only the HT29 colon cancer xenograft demonstrated uptake. Subsequent qPCR analysis showed that the other xenografts had high levels of matriptase’s endogenous inhibitor potentially inactivating matriptase. The 111In labeled agent was an excellent SPECT imaging agent in the HT29 xenograft and in the PDX model with a 28.3% ID/g at 72hrs in HT29. Immunofluoresence studies revealed active matriptase to be present in both primary colon cancer tumors and in hepatic metastases tissue. Conclusions Using our novel antibody inhibitor probe, active matriptase was imaged in different models of human colon cancer. These data suggest that active matriptase is a common feature of colon cancer and active matriptase is an indication that cancer is present and potentially metastatic