Department of Radiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Graduate Biomedical Sciences, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Molecules. 2021 Mar 12;26(6):1568. doi: 10.3390/molecules26061568.
Paclitaxel (PTX) treatment efficacy varies in breast cancer, yet the underlying mechanism for variable response remains unclear. This study evaluates whether human epidermal growth factor receptor 2 (HER2) expression level utilizing advanced molecular positron emission tomography (PET) imaging is correlated with PTX treatment efficacy in preclinical mouse models of HER2+ breast cancer. HER2 positive (BT474, MDA-MB-361), or HER2 negative (MDA-MB-231) breast cancer cells were subcutaneously injected into athymic nude mice and PTX (15 mg/kg) was administrated. In vivo HER2 expression was quantified through [Zr]-pertuzumab PET/CT imaging. PTX treatment response was quantified by [F]-fluorodeoxyglucose ([F]-FDG) PET/CT imaging. Spearman's correlation, Kendall's tau, Kolmogorov-Smirnov test, and ANOVA were used for statistical analysis. [Zr]-pertuzumab mean standard uptake values (SUV) of BT474 tumors were 4.9 ± 1.5, MDA-MB-361 tumors were 1.4 ± 0.2, and MDA-MB-231 (HER2-) tumors were 1.1 ± 0.4. [F]-FDG SUV changes were negatively correlated with [Zr]-pertuzumab SUV (r = -0.5887, = 0.0030). The baseline [F]-FDG SUV was negatively correlated with initial [Zr]-pertuzumab SUV (r = -0.6852, = 0.0002). This study shows PTX treatment efficacy is positively correlated with HER2 expression level in human breast cancer mouse models. Molecular imaging provides a non-invasive approach to quantify biological interactions, which will help in identifying chemotherapy responders and potentially enhance clinical decision-making.
紫杉醇 (PTX) 治疗疗效在乳腺癌中存在差异，但对于这种差异的潜在机制仍不清楚。本研究评估了利用先进的分子正电子发射断层扫描 (PET) 成像技术评估人表皮生长因子受体 2 (HER2) 表达水平是否与 HER2+乳腺癌的临床前小鼠模型中的 PTX 治疗疗效相关。将 HER2 阳性 (BT474、MDA-MB-361) 或 HER2 阴性 (MDA-MB-231) 乳腺癌细胞皮下注射到裸鼠中，并给予 PTX (15mg/kg)。通过 [Zr]-曲妥珠单抗 PET/CT 成像定量测定体内 HER2 表达。通过 [F]-氟脱氧葡萄糖 ([F]-FDG) PET/CT 成像定量测定 PTX 治疗反应。使用 Spearman 相关、Kendall's tau、Kolmogorov-Smirnov 检验和 ANOVA 进行统计分析。BT474 肿瘤的 [Zr]-曲妥珠单抗平均标准摄取值 (SUV) 为 4.9 ± 1.5，MDA-MB-361 肿瘤为 1.4 ± 0.2，而 MDA-MB-231(HER2-)肿瘤为 1.1 ± 0.4。[F]-FDG SUV 变化与 [Zr]-pertuzumab SUV 呈负相关 (r = -0.5887, = 0.0030)。基线 [F]-FDG SUV 与初始 [Zr]-pertuzumab SUV 呈负相关 (r = -0.6852, = 0.0002)。本研究表明，在人乳腺癌小鼠模型中，PTX 治疗疗效与 HER2 表达水平呈正相关。分子成像提供了一种非侵入性的方法来定量测定生物相互作用，这将有助于识别化疗反应者，并可能增强临床决策。
