Immunotargeting of Integrin α6β4 for Single-Photon Emission Computed Tomography and Near-Infrared Fluorescence Imaging in a Pancreatic Cancer Model

Mol Imaging. 2016 Jan 29:15:1536012115624917. doi: 10.1177/1536012115624917. Print 2016.

Abstract

To explore suitable imaging probes for early and specific detection of pancreatic cancer, we demonstrated that α6β4integrin is a good target and employed single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging for immunotargeting. Expression levels of α6β4were examined by Western blotting and flow cytometry in certain human pancreatic cancer cell lines. The human cell line BxPC-3 was used for α6β4-positive and a mouse cell line, A4, was used for negative counterpart. We labeled antibody against α6β4with Indium-111 ((111)In) or indocyanine green (ICG). After injection of(111)In-labeled probe to tumor-bearing mice, biodistribution, SPECT, autoradiography (ARG), and immunohistochemical (IHC) studies were conducted. After administration of ICG-labeled probe, in vivo and ex vivo NIR imaging and fluorescence microscopy of tumors were performed. BxPC-3 tumor showed a higher radioligand binding in SPECT and higher fluorescence intensity as well as a delay in the probe washout in NIR imaging when compared to A4 tumor. The biodistribution profile of(111)In-labeled probe, ARG, and IHC confirmed the α6β4specific binding of the probe. Here, we propose that α6β4is a desirable target for the diagnosis of pancreatic cancer and that it could be detected by radionuclide imaging and NIR imaging using a radiolabeled or ICG-labeled α6β4antibody.

Keywords: 111In SPECT; ICG; NIR imaging; integrin α6β4; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology*
  • Cell Line, Tumor
  • Early Detection of Cancer
  • Humans
  • Indium Radioisotopes
  • Integrin alpha6beta4 / immunology*
  • Mice
  • Molecular Imaging / methods*
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / metabolism*
  • Tomography, Emission-Computed, Single-Photon / methods

Substances

  • Antibodies, Monoclonal
  • Indium Radioisotopes
  • Integrin alpha6beta4