Abstract
PurposeDetecting 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 in vivo to study properties that may be able to detect cancer death.ResultsUsing 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 (p < 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.ConclusionsCEST 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 in vivo tumor model.Materials and MethodsBreast 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.
Highlights
Advanced breast cancer is an aggressive form of cancer associated with poor survival and high risk of recurrence [1]
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 (p < 0.0001) between viable tumor and cell death regions, matching patterns seen on histology
Summary
Advanced breast cancer is an aggressive form of cancer associated with poor survival and high risk of recurrence [1]. Modern treatment approaches increasingly use chemotherapy before surgery (“neoadjuvant chemotherapy”) followed by radiotherapy [2]. The degree of tumor response to chemotherapy correlates with survival outcomes [3]. Standard response assessment uses anatomical measurements of tumor size but some cancer, does not respond, which may lead to 4–6 months of ineffective treatment associated with harmful side effects [4,5,6]. A method to detect response to chemotherapy early in a treatment course, such as by detecting cell death, would allow for a change in therapy for non-responders, potentially improving outcomes. Various imaging techniques have been studied for their ability to predict tumor response.
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