Dataset Information

CF750-A33scFv-Fc-Based Optical Imaging of Subcutaneous and Orthotopic Xenografts of GPA33-Positive Colorectal Cancer in Mice.

ABSTRACT: Antibody-based imaging agents are attractive as adjuvant diagnostic tools for solid tumors. GPA33 is highly expressed in most human colorectal cancers and has been verified as a diagnostic and therapeutic target. Here, we built an A33scFv-Fc antibody against GPA33 by fusing A33scFv to the Fc fragment of human IgG1 antibodies. The A33scFv-Fc specifically binds GPA33-positive colorectal cancer cells and tumor tissues. After the intravenous injection of mice bearing subcutaneous GPA33-positive LS174T tumor grafts with near-infrared fluorescence probe CF750-labeled A33scFv-Fc (CF750-A33scFv-Fc), high contrast images of the tumor grafts could be kinetically documented within 24?h using an optical imaging system. However, GPA33-negative SMMC7721 tumor grafts could not be visualized by injecting the same amount of CF750-A33scFv-Fc. Moreover, in subcutaneous LS174T tumor-bearing mice, tissue scanning revealed that the CF750-A33scFv-Fc accumulated in the tumor grafts, other than the kidney and liver. In mice with orthotopic tumor transplantations, excrescent LS174T tumor tissues in the colon were successfully removed under guidance by CF750-A33scFv-Fc-based optical imaging. These results indicate that CF750-A33scFv-Fc can target GPA33, suggesting the potential of CF750-A33scFv-Fc as an imaging agent for the diagnosis of colorectal cancer.

SUBMITTER: Wei D

PROVIDER: S-EPMC4454727 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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CF750-A33scFv-Fc-Based Optical Imaging of Subcutaneous and Orthotopic Xenografts of GPA33-Positive Colorectal Cancer in Mice.

Wei Danfeng D Fan Qing Q Cai Huawei H Yang Hao H Wan Lin L Li Lin L Lu Xiaofeng X

BioMed research international 20150521

Antibody-based imaging agents are attractive as adjuvant diagnostic tools for solid tumors. GPA33 is highly expressed in most human colorectal cancers and has been verified as a diagnostic and therapeutic target. Here, we built an A33scFv-Fc antibody against GPA33 by fusing A33scFv to the Fc fragment of human IgG1 antibodies. The A33scFv-Fc specifically binds GPA33-positive colorectal cancer cells and tumor tissues. After the intravenous injection of mice bearing subcutaneous GPA33-positive LS17 ...[more]

PMID: 26090413

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Project description:INTRODUCTION:The ?v?3 integrin, which is expressed by angiogenic epithelium and some tumor cells, is an attractive target for the development of both imaging agents and therapeutics. While optimal implementation of ?v?3-targeted therapeutics will require a priori identification of the presence of the target, the clinical evaluation of these compounds has typically not included parallel studies with ?v?3-targeted diagnostics. This is at least partly due to the relatively limited availability of PET radiopharmaceuticals in comparison to those labeled with (99m)Tc. In an effort to begin to address this limitation, we evaluated the tumor uptake of (99m)Tc-NC100692, a cyclic RGD peptide that binds to ?v?3 with ~1-nM affinity, in an ?v?3-positive tumor model as well as its in vivo specificity. METHODS:MicroSPECT imaging was used to assess the ability of cilengitide, a therapeutic with high affinity for ?v?3, to block and displace (99m)Tc-NC100692 in an orthotopic U87 glioma tumor. The specificity of (99m)Tc-NC100692 was quantitatively evaluated in mice bearing subcutaneous U87MG tumors, by comparison of the biodistribution of (99m)Tc-NC100692 with that of the non-specific structural analogue (99m)Tc-AH-111744 and by blocking uptake of (99m)Tc-NC100692 with excess unlabeled NC100692. RESULTS:MicroSPECT imaging studies demonstrated that uptake of (99m)Tc-NC100692 in the intracranial tumor model was both blocked and displaced by the ?v?3-targeted therapeutic cilengitide. Biodistribution studies provided quantitative confirmation of these imaging results. Tumor uptake of (99m)Tc-NC100692 at 1h post-injection was 2.8 ± 0.7% ID/g compared to 0.38 ± 0.1% ID/g for (99m)Tc-AH-111744 (p < 0.001). Blocking (99m)Tc-NC100692 uptake by pre-injecting the mice with excess unlabeled NC100692 reduced tumor uptake by approximately five-fold, to 0.68 ± 0.3% ID/g (p = 0.01). CONCLUSION:These results confirm that (99m)Tc-NC100692 does, in fact, target the ?v?3 integrin and may, therefore, be useful in identifying patients prior to anti-?v?3 therapy as well as monitoring the response of these patients to therapy.

Dataset Information

CF750-A33scFv-Fc-Based Optical Imaging of Subcutaneous and Orthotopic Xenografts of GPA33-Positive Colorectal Cancer in Mice.

Publications

CF750-A33scFv-Fc-Based Optical Imaging of Subcutaneous and Orthotopic Xenografts of GPA33-Positive Colorectal Cancer in Mice.

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