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

Author:

Turner Michael A.12ORCID,Cox Kristin E.12ORCID,Neel Nicholas12,Amirfakhri Siamak12,Nishino Hiroto12,Clary Bryan M.1,Hosseini Mojgan3,Natarajan Gopalakrishnan4,Mallya Kavita4,Mohs Aaron M.456,Hoffman Robert M.127ORCID,Batra Surinder K.4ORCID,Bouvet Michael1ORCID

Affiliation:

1. Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USA

2. VA San Diego Healthcare System, La Jolla, CA 92161, USA

3. Department of Pathology, University of California San Diego, La Jolla, CA 92037, USA

4. Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE 68198, USA

5. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA

6. Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68105, USA

7. AntiCancer, Inc., San Diego, CA 92111, USA

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.

Funder

VA Merit Review

National Institutes of Health

National Institute of Health Training Grant

National Cancer Institute Cancer Center Support Grant

Publisher

MDPI AG

Subject

Medicine (miscellaneous)

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