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

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