Potential of PET to Predict the Response to Trastuzumab Treatment in an ErbB2-Positive Human Xenograft Tumor Model

Journal of Nuclear Medicine

Anthony Kong¹  Dale O. Kiesewetter¹  Gabriela Kramer-Marek¹  Ruth Bennett¹  Merel Gijsen¹  Ioannis Roxanis¹  Rafal Zielinski¹  Jacek Capala¹ 

关键词: breast cancer HER2/ErbB2;    trastuzumab;    PET imaging;    Affibody molecules;   

DOI  :  10.2967/jnumed.111.096685

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Currently, an alteration in the gross volume of a tumor is used to assess its response to trastuzumab; however, this approach provides only a late indication of response. Tissue-sample ex vivo assays are potentially valuable, but their procurement through biopsies is invasive and might be biased by tumor heterogeneity. We studied the feasibility of using PET to quantify changes in ErbB2 (HER2/neu) expression and to predict the response to trastuzumab in BT474 breast cancer xenografts with N-[2-(4-18F-fluorobenzamido)ethyl]maleimide (18F-FBEM)-HER2:342 Affibody. Methods: Mice bearing BT474 tumors were given trastuzumab (50 mg/kg loading dose, 25 mg/kg maintenance dose, administered intraperitoneally twice a week) or saline (control) for a total of 5 doses. Tumor size was monitored twice a week. Animals were scanned before the treatment, at 48 h, and 2 wk after the beginning of therapy. After the final scan, PET results were correlated with tumor response and immunohistochemical assessment of ErbB2 level, as well as with vasculature in the treated tumors. Results: Analysis of PET images indicated that tracer uptake was significantly reduced after 1 dose of trastuzumab, compared with baseline, suggesting applicability as an early indicator of changes in ErbB2 expression. After 5 doses of trastuzumab, the overall decrease in 18F-FBEM-HER2:342 Affibody uptake also correlated with tumor response and downregulation of ErbB2 expression by immunohistochemical assessment. However, individual animals had different responses. There was a correlation between bigger PET changes and a higher vessel count in the tumors, suggesting that an increased number of vessels could lead to better trastuzumab delivery. We confirmed that the difference in average vessel count in the tumors was not related to the size of the tumors and therefore was not due to the selection of more vascular tumors. This finding is consistent with previous findings demonstrating that the number of vessels in a tumor could be a useful prognostic marker for treatment response. Conclusion: Our data suggest that Affibody-based PET can noninvasively provide specific information on changes in receptor expression and could be a valuable strategy for predicting tumor response to trastuzumab.

【 授权许可】

Unknown