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

Michael A Turner; Kristin E Cox; Nicholas Neel; Siamak Amirfakhri; Hiroto Nishino; Bryan M Clary; Mojgan Hosseini; Gopalakrishnan Natarajan; Kavita Mallya; Aaron M Mohs; Robert M Hoffman; Surinder K Batra; Michael Bouvet

doi:10.3390/jpm13050857

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

J Pers Med. 2023 May 20;13(5):857. doi: 10.3390/jpm13050857.

Authors

Michael A Turner^{1

2}, Kristin E Cox^{1

2}, Nicholas Neel^{1

2}, Siamak Amirfakhri^{1

2}, Hiroto Nishino^{1

2}, Bryan M Clary¹, Mojgan Hosseini³, Gopalakrishnan Natarajan⁴, Kavita Mallya⁴, Aaron M Mohs^{4

5

6}, Robert M Hoffman^{1

2

7}, Surinder K Batra⁴, Michael Bouvet¹

Affiliations

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.

Keywords: fluorescent antibody; imaging; liver metastasis; mucin; pancreatic cancer; selective targeting.

Abstract

Grants and funding