Evaluation of the efficacy of a Met tyrosine kinase inhibitor (TKI) in human gastric carcinoma (MKN-45) mouse xenografts using a [99mTc]labeled peptide ([99mTc]Met) targeting the Met receptor (Met)

332 Objectives The aberrant activation of hepatocyte growth factor receptor protein (Met) in a variety of cancers has been linked to increased proliferation and progression to metastatic disease. Met-directed TKIs have shown therapeutic potential thus an imaging agent targeting Met could aid in patient selection and in monitoring responses to Met-targeted therapies. MKN-45 cell (high Met expression, MKN) xenografts treated with a Met TKI (TX) or vehicle (Vh) were imaged for changes in tumor Met status and volumes using [99mTc]Met or ultrasound (US), respectively. Methods MKN xenografts treated with the Met TKI, PHA 665752 (TX), or Vh were imaged using SPECT/US before treatment (Day 0) and then at Day(D) 8, 14, and 21 following treatment. SPECT imaging was performed 90 min post injection and tumor uptakes (%ID/g) were determined. Tumor samples were taken at D21 for analysis of Met content and histopathology. Results Significant decreases (~40%) in mean [99mTc]Met tumor uptakes were observed in the TX vs Vh groups at D8 and 14 but not at D21 (~25%). Mean US tumor volumes were significantly decreased 36% and 55% at D14 and 21, respectively in TX vs Vh but not at D8 (26%). Met content in D21 tumor samples was significantly decreased (~50%) in TX vs Vh which correlated with imaging results. Substantial necrosis was observed in these samples for both groups; necrosis in the Vh tumors was associated with large tumor sizes (0.5 to 1.6 g), and may explain the lack of a significant decrease of [99mTc]Met tumor uptakes in TX vs Vh at D21. Conclusions Both [99mTc]Met and US were able to detect efficacy of a Met TKI in MKN tumors but [99mTc]Met exhibited significantly decreased uptakes earlier in TX groups. These data suggest that [99mTc]Met imaging may better detect early changes in Met content, thereby providing a more sensitive readout of therapeutic response