Klein Jonathan, Lam Wilfred W, Czarnota Gregory J, Stanisz Greg J
Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Oncotarget. 2018 Jul 31;9(59):31490-31501. doi: 10.18632/oncotarget.25844.
Detecting cell death and predicting tumor response early in a course of chemotherapy could help optimize treatment regimens and improve clinical outcomes. Chemical exchange saturation transfer (CEST) MRI was investigated to study properties that may be able to detect cancer death.
Using a magnetization transfer ratio (MTR) cutoff of 0.12 at 1.8 ppm was able to differentiate between viable tumor and cell death regions. Comparison of MTR values at this frequency showed significant differences ( < 0.0001) between viable tumor and cell death regions, matching patterns seen on histology. Using this cutoff, the mean increase in cell death index (± standard error of the mean) after chemotherapy was 4 ± 4%, 10% ± 7%, 10 ± 8%, and 4 ± 9% at 4, 8, 12, and 24 h, respectively.
CEST MRI can detect cell death in MDA-231 xenografts but further work is needed to characterize the clinical applications of this finding. Maximum response to chemotherapy occurred at 8-12 h after chemotherapy injection in this tumor model.
Breast cancer xenografts (MDA-MB-231) were scanned using 7 T MRI before and after chemotherapy. As a measure of CEST effect at 0.5 µT saturation amplitude, MTR values at frequency offsets of 1.8 and -3.3 ppm were evaluated. CEST signals after chemotherapy treatment were compared to cell-death histopathology of tumors.
在化疗过程中早期检测细胞死亡并预测肿瘤反应有助于优化治疗方案并改善临床结果。研究了化学交换饱和转移（CEST）磁共振成像（MRI）以探究可能能够检测癌症细胞死亡的特性。
使用1.8 ppm处0.12的磁化转移率（MTR）临界值能够区分存活肿瘤和细胞死亡区域。该频率下MTR值的比较显示，存活肿瘤和细胞死亡区域之间存在显著差异（<0.0001），与组织学上观察到的模式相符。使用此临界值，化疗后4、8、12和24小时的细胞死亡指数平均增加（±平均标准误差）分别为4±4%、10%±7%、10±8%和4±9%。
CEST MRI可检测MDA - 231异种移植瘤中的细胞死亡，但需要进一步开展工作来明确这一发现的临床应用。在该肿瘤模型中，化疗注射后8 - 12小时出现最大化疗反应。
使用7T MRI对乳腺癌异种移植瘤（MDA - MB - 231）化疗前后进行扫描。作为0.5μT饱和幅度下CEST效应的一种测量方法，评估了1.8和 - 3.3 ppm频率偏移处的MTR值。将化疗治疗后的CEST信号与肿瘤的细胞死亡组织病理学进行比较。
