Non-invasive imaging of C-MET receptor for delineation of liver metastasis of colorectal cancer

Objectives Approximately 20%-25% of patients with colorectal cancer (CRC) have liver metastases at the time of diagnosis. The prognosis of CRC is dependent on accurate diagnosis at the time of biopsy as well as the efficiency of liver cytoreductive surgery. C-Met is a proto-oncogene overexpressing in 70-86 % of CRC and can be effectively used to detect metastatic foci of CRC to liver. Our aim was to assess whether optical imaging of c-Met using a targeted fluorescence probe, GE-137, can be used to delineate intrahepatic CRC metastasis and be effectively employed for intraoperative and minimally invasive interventions.

Methods A focal model of CRC metastasis to liver was generated by injection of human CRC cells (HT-29) in the hepatic subcapsular space in nu/nu mice (n=8). Multispectral epifluorescence imaging was performed over 8 hours following GE-137 probe injection and uptake in the liver and tumor, and tumor to background ratio (TBR) were calculated. Biodistribution study was performed to evaluate NIR signal in different organs1 hour after probe injection. IHC evaluation of c-Met expression in human CRCs was performed using a tissue array.

Results Surface epifluorescence imaging showed high uptake in subcapsularly grown tumors with the maximum intensity 1 hour after injection. While the signal intensity in both liver and xenograft tumor decreased afterwards, TBR increased constantly (1.41±0.14, 5 min vs. 5.29±1.59, 8 hours after injection). Tumor to background liver signal reached a peak of 15.28±0.9, 1 hour post-injection. Biodistribution study demonstrated low NIR signal in normal liver tissue. IHC confirmed elevated expression of c-MET in 81% of CRC samples.

Conclusions High tumor to normal liver fluorescence ratios in our tumor model using GE-137 and overexpression of c-MET in most of human CRC tumors suggest that optical imaging of c-MET is a promising and translatable approach for early detection of liver metastases from CRC and for intraoperative and minimally invasive image-guided interventions.