Imaging biomarkers predict response to anti-HER2 (ErbB2) therapy in preclinical models of breast cancer

影像生物标志物可预测乳腺癌临床前模型对抗 HER2 (ErbB2) 治疗的反应

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作者:Chirayu Shah, Todd W Miller, Shelby K Wyatt, Eliot T McKinley, Maria Graciela Olivares, Violeta Sanchez, Donald D Nolting, Jason R Buck, Ping Zhao, M Sib Ansari, Ronald M Baldwin, John C Gore, Rachel Schiff, Carlos L Arteaga, H Charles Manning

Conclusions

Molecular imaging of apoptosis accurately predicts trastuzumab-induced regression of HER2+ tumors and may warrant clinical exploration to predict early response to neoadjuvant trastuzumab. Trastuzumab does not seem to alter glucose metabolism substantially enough to afford [18F]FDG-PET significant predictive value in this setting. Although promising in one preclinical model, further studies are required to determine the overall value of [18F]FLT-PET as a biomarker of response to trastuzumab in HER2+ breast cancer.

Purpose

To evaluate noninvasive imaging

Results

NIR700-Annexin V accumulated significantly in trastuzumab-treated MMTV/HER2 and BT474 tumors that ultimately regressed but not in nonresponding or vehicle-treated tumors. Uptake of [18F]FDG was not affected by trastuzumab treatment in MMTV/HER2 or BT474 tumors. [18F]FLT-PET imaging predicted trastuzumab response in BT474 tumors but not in MMTV/HER2 tumors, which exhibited modest uptake of [18F]FLT. Close agreement was observed between imaging metrics and immunohistochemical analysis. Conclusions: Molecular imaging of apoptosis accurately predicts trastuzumab-induced regression of HER2+ tumors and may warrant clinical exploration to predict early response to neoadjuvant trastuzumab. Trastuzumab does not seem to alter glucose metabolism substantially enough to afford [18F]FDG-PET significant predictive value in this setting. Although promising in one preclinical model, further studies are required to determine the overall value of [18F]FLT-PET as a biomarker of response to trastuzumab in HER2+ breast cancer.

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