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• W2044366912 abstract "Human epidermal growth factor receptor 1 (<i>HER1</i>) plays an important role in the pathogenesis of colorectal cancer. Panitumumab is an anti-<i>HER1</i> monoclonal antibody approved for use in colorectal cancer. However, few data exist regarding <i>HER1</i> status in the corresponding distant metastases, and little corresponding information is available regarding the localization of panitumumab at primary and metastatic lesions. The utility of PET and MRI using ⁸⁹Zr-panitumumab to assess the status of <i>HER1</i> in distant metastases with different metastasis models is presented in this study. <b>Methods:</b> In vivo biodistribution and PET studies were performed in <i>HER1</i>-expressing LS-174T and <i>HER1</i>-negative A375 tumor xenografts. Additionally, studies were performed in different models of intraperitoneal and pulmonary metastases. MRI studies were performed for metastatic models to characterize the targeting potential of ⁸⁹Zr-panitumumab at different lesion sites. <b>Results:</b><i>HER1</i>-mediated targeting was achieved in all <i>HER1</i>-expressing models. The LS-174T tumor area under the curve (AUC) was 3.7-fold greater than the AUC for A375. The LS-174T tumor AUC of 204.13 ± 9.67 was significantly greater (<i>P</i> < 0.001) than the LS-174T tumor AUC of 36.45 ± 1.39 obtained from mice coinjected with 0.1 mg of panitumumab for blocking the target. Differences were observed in 2 intraperitoneal models; tumor uptake in mice with a 3-d tumor burden was more than 2-fold greater than the mice with a 7-d tumor burden. PET and MRI studies revealed <i>HER1</i>-mediated tumor targeting in all metastatic models. However, significant differences were observed between different LS-174T tumor models. Peak tumor uptake of approximately 40 percentage injected dose per gram (%ID/g) was observed at 3–4 d after injection for the subcutaneous tumor model, in contrast to approximately 75 %ID/g at 2 d after injection for the thoracic tumors and approximately 95 %ID/g at 1–2 d after injection for the intraperitoneal tumors. <b>Conclusion:</b> The potential utility of ⁸⁹Zr-panitumumab in assessing <i>HER1</i> status in distant metastases and understanding the variations in antibody uptake at different lesion sites is demonstrated in this study. ⁸⁹Zr-panitumumab can play a vital role in patient stratification and immunotherapy and therefore warrants further investigation for clinical translation." @default.
• W2044366912 created "2016-06-24" @default.
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• W2044366912 date "2012-01-01" @default.
• W2044366912 modified "2023-10-16" @default.
• W2044366912 title "PET and MRI of Metastatic Peritoneal and Pulmonary Colorectal Cancer in Mice with Human Epidermal Growth Factor Receptor 1–Targeted ⁸⁹Zr-Labeled Panitumumab" @default.
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• W2044366912 doi "https://doi.org/10.2967/jnumed.111.094169" @default.
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