Hui Wang1, Dan Li2, Shuanglong Liu3, Ren Liu4, Hong Yuan1, Valery Krasnoperov5, Hong Shan6, Peter S Conti3, Parkash S Gill4, Zibo Li7. 1. Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 2. Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, California Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangzhou, China ziboli@med.unc.edu shanhong@mail.sysu.edu.cn. 3. Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, California. 4. Department of Pathology, University of Southern California, Los Angeles, California; and. 5. Vasgene Therapeutics Inc., Los Angeles, California. 6. Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangzhou, China ziboli@med.unc.edu shanhong@mail.sysu.edu.cn. 7. Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina Molecular Imaging Center, Department of Radiology, University of Southern California, Los Angeles, California ziboli@med.unc.edu shanhong@mail.sysu.edu.cn.
Abstract
UNLABELLED: 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.
UNLABELLED: 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 tumorGRP78 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.
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