Highly Selective Targeting of Pancreatic Cancer in the Liver with a Near-Infrared Anti-MUC5AC Probe in a PDOX Mouse Model: A Proof-of-Concept Study

Abstract

Accurately identifying metastatic disease is critical to directing the appropriate treatment in pancreatic cancer. Mucin 5AC is overexpressed in pancreatic cancer but absent in normal pancreas tissue. The present proof-of-concept study demonstrates the efficacy of an anti-mucin 5AC antibody conjugated to an IR800 dye (MUC5AC-IR800) to preferentially label a liver metastasis of pancreatic cancer (Panc Met) in a unique patient-derived orthotopic xenograft (PDOX) model. In orthotopic models, the mean tumor to background ratio was 1.787 (SD ± 0.336), and immunohistochemistry confirmed the expression of MUC5AC within tumor cells. MUC5AC-IR800 provides distinct visualization of pancreatic cancer liver metastasis in a PDOX mouse model, demonstrating its potential utility in staging laparoscopy and fluorescence-guided surgery.

Targeting Patient-Derived Orthotopic Gastric Cancers with a Fluorescent Humanized Anti-CEA Antibody

“…The efficacy of antibodies conjugated to NIR fluorophores to label and enhance the detection of breast, lung, pancreatic, prostate, and colorectal cancers have been demonstrated in preclinical mouse models. [7][8][9][10][11][12][13][14][15][16][17][18][19][20] Several of these studies have now been translated to human trials, which have shown that the use of tumorspecific fluorescence labeling can detect additional residual tumor deposits or previously unrecognized synchronous disease in 14-50% of cases. [21][22][23][24][25] However, there are currently no FDA-approved agents for FGS of gastric cancer.…”