Abstract
The overexpression of the GRP78 receptor on cell surface has been linked with the tumor growth, metastasis, and resistance to therapy. Based on a novel anti-GRP78 monoclonal antibody (MAb159), we developed a 64Cu-labeled probe for positron emission tomography (PET) imaging of tumor GRP78 expression. Methods: MAb159 was conjugated with the 64Cu-chelator DOTA through lysine’s on the antibody. DOTA-hIgG was also prepared as a control, which did not bind to GRP78. The resulting PET probes were evaluated in BxPC-3 pancreatic cancer xenografts in athymic nude mice. Results: The radiotracer was synthesized with a specific activity of 0.8MBq/µg antibody. In BxPC3 xenografts, 64Cu-DOTA-MAb159 demonstrated prominent tumor accumulation (4.3 ± 1.2, 15.4 ± 2.6, and 18.3 ± 1.0%ID/g at 1, 17, and 48 post injection, respectively). In contrast, 64Cu-DOTA-hIgG had low BxPC3 tumor accumulation (4.8 ± 0.5, 7.5 ± 0.7, and 4.6 ± 0.8ID/g at 1, 17, and 48 h post injection, respectively). Conclusion: We have demonstrated that GRP78 could serve as a valid target for pancreatic cancer imaging. The success of this approach would be valuable to evaluate disease course and therapeutic efficacy at the earliest stages of anti-GRP78 treatment. Moreover, these newly developed probes could have important applications in other cancer types overexpressing GRP78.
- Animal Imaging
- Molecular Imaging
- Monoclonal Antibodies
- Oncology: Pancreas
- PET
- PET/CT
- Radiochemistry
- Radiopharmaceuticals
- 64Cu
- GRP78
- PET
- Pancreatic Cancer
- Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.