Small-Animal PET Imaging of Pancreatic Cancer Xenografts Using a 64Cu-Labeled Monoclonal Antibody, MAb159

J Nucl Med. 2015 Jun;56(6):908-13. doi: 10.2967/jnumed.115.155812. Epub 2015 Apr 23.

Abstract

Overexpression of the GRP78 receptor on cell surfaces has been linked with tumor growth, metastasis, and resistance to therapy. We developed a (64)Cu-labeled probe for PET imaging of tumor GRP78 expression based on a novel anti-GRP78 monoclonal antibody, MAb159.

Methods: MAb159 was conjugated with the (64)Cu-chelator DOTA through lysines on the antibody. DOTA-human IgG was also prepared as a control that did not bind to GRP78. The resulting PET probes were evaluated in BXPC3 pancreatic cancer xenografts in athymic nude mice.

Results: The radiotracer was synthesized with a specific activity of 0.8 MBq/μg of antibody. In BXPC3 xenografts, (64)Cu-DOTA-MAb159 demonstrated prominent tumor accumulation (4.3 ± 1.2, 15.4 ± 2.6, and 18.3 ± 1.0 percentage injected dose per gram at 1, 17, and 48 after injection, respectively). In contrast, (64)Cu-DOTA-human IgG had low BXPC3 tumor accumulation (4.8 ± 0.5, 7.5 ± 0.7, and 4.6 ± 0.8 percentage injected dose per gram at 1, 17, and 48 h after injection, respectively).

Conclusion: We demonstrated that GRP78 can serve as a valid target for pancreatic cancer imaging. The success of this approach will be valuable for evaluating disease course and therapeutic efficacy at the earliest stages of anti-GRP78 treatment. Moreover, these newly developed probes may have important applications in other types of cancer overexpressing GRP78.

Keywords: 64Cu; GRP78; PET; pancreatic cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / chemistry*
  • Cell Line, Tumor
  • Copper Radioisotopes*
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Heat-Shock Proteins / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Immunoglobulin G / chemistry
  • Mice
  • Mice, Nude
  • Microscopy, Fluorescence
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / pathology*
  • Positron-Emission Tomography*
  • Radiopharmaceuticals*
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal, Humanized
  • Copper Radioisotopes
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Heterocyclic Compounds, 1-Ring
  • Hspa5 protein, mouse
  • Immunoglobulin G
  • Radiopharmaceuticals
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid