Presentation Title

CEST used to monitor Bevacizumab treatment against Glioblastoma

Faculty Mentor

Jingwen Yao

Start Date

17-11-2018 8:45 AM

End Date

17-11-2018 9:00 AM

Location

C302

Session

Oral 1

Type of Presentation

Oral Talk

Subject Area

health_nutrition_clinical_science

Abstract

Glioblastoma (GBM) is both the most common and the most deadly type of malignant glioma. Median survival post-diagnosis is approximately a year and fewer than 5% survive more than five years (Gallego 2015) despite aggressive therapy including surgery, radiation, and chemotherapy. Treatment with Bevacizumab is a common therapy for recurrent GBM, usually administered in conjunction with other types of chemotherapy (Rinne 2013). Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which prevents new angiogenesis and reduces the existing abnormal vasculature within GBM. (Gil 2013)

Non-invasive biomarkers to predict therapeutic outcome and assess early treatment response are highly desired for guiding individualized treatment planning. (Sagiyama 2014) In this study, we investigated the use of a novel pH-dependent MRI technique termed amine Chemical Exchange Saturation Transfer (CEST), as a potential biomarker for treatment response to Bevacizumab. Amine CEST is sensitive to both high amino acid concentration and low pH, which are both indicators of abnormal tumor metabolism. High levels of metabolism in tumor regions acidify the tissue through accumulation of lactic acid (Harris 2015), which enhances the CEST contrast through altering the exchange rate between amine protons and water protons (Wu 2016).

A total of 8 male and 3 female GBM patients from the ages of 45 to 75 years old undergoing Bevacizumab treatment were scanned with CEST MRI before and after treatment in the current pilot study. We calculated the magnetization transfer ratio asymmetry (MTRasym) at amine proton resonance frequency (3.0ppm) as the metric of CEST contrast. We observed a significant decrease in MTRasym after Bevacizumab treatment (p < 0.0001, t-test). This change in MTRasym has a significant correlation with the volumetric change of tumor (R = 0.607, p = 0.048) as well as with progression free survival (PFS) (R = -0.677, p = 0.022). In most cases (8 out of 11), we observed that residual high MTRasym regions post treatment colocalize with the recurrence site of brain tumors, months before they could be observed on conventional MR images.

These promising preliminary results indicate that amineCEST imaging has potential to significantly impact how GBM treatment is monitored.

Summary of research results to be presented

Non-invasive biomarkers to predict therapeutic outcome and assess early treatment response are highly desired for guiding individualized treatment planning. (Sagiyama 2014) In this study, we investigated the use of a novel pH-dependent MRI technique termed amine Chemical Exchange Saturation Transfer (CEST), as a potential biomarker for treatment response to Bevacizumab. Amine CEST is sensitive to both high amino acid concentration and low pH, which are both indicators of abnormal tumor metabolism. High levels of metabolism in tumor regions acidify the tissue through accumulation of lactic acid (Harris 2015), which enhances the CEST contrast through altering the exchange rate between amine protons and water protons (Wu 2016).

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Nov 17th, 8:45 AM Nov 17th, 9:00 AM

CEST used to monitor Bevacizumab treatment against Glioblastoma

C302

Glioblastoma (GBM) is both the most common and the most deadly type of malignant glioma. Median survival post-diagnosis is approximately a year and fewer than 5% survive more than five years (Gallego 2015) despite aggressive therapy including surgery, radiation, and chemotherapy. Treatment with Bevacizumab is a common therapy for recurrent GBM, usually administered in conjunction with other types of chemotherapy (Rinne 2013). Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which prevents new angiogenesis and reduces the existing abnormal vasculature within GBM. (Gil 2013)

Non-invasive biomarkers to predict therapeutic outcome and assess early treatment response are highly desired for guiding individualized treatment planning. (Sagiyama 2014) In this study, we investigated the use of a novel pH-dependent MRI technique termed amine Chemical Exchange Saturation Transfer (CEST), as a potential biomarker for treatment response to Bevacizumab. Amine CEST is sensitive to both high amino acid concentration and low pH, which are both indicators of abnormal tumor metabolism. High levels of metabolism in tumor regions acidify the tissue through accumulation of lactic acid (Harris 2015), which enhances the CEST contrast through altering the exchange rate between amine protons and water protons (Wu 2016).

A total of 8 male and 3 female GBM patients from the ages of 45 to 75 years old undergoing Bevacizumab treatment were scanned with CEST MRI before and after treatment in the current pilot study. We calculated the magnetization transfer ratio asymmetry (MTRasym) at amine proton resonance frequency (3.0ppm) as the metric of CEST contrast. We observed a significant decrease in MTRasym after Bevacizumab treatment (p < 0.0001, t-test). This change in MTRasym has a significant correlation with the volumetric change of tumor (R = 0.607, p = 0.048) as well as with progression free survival (PFS) (R = -0.677, p = 0.022). In most cases (8 out of 11), we observed that residual high MTRasym regions post treatment colocalize with the recurrence site of brain tumors, months before they could be observed on conventional MR images.

These promising preliminary results indicate that amineCEST imaging has potential to significantly impact how GBM treatment is monitored.