5-ALA Work Selected as Highlight Talk for WMIC

The World Molecular Imaging Society is an international scientific society dedicated to the understanding of biology and medicine through multimodal in vivo imaging of cellular and molecular events involved in normal and pathologic processes and utilization of quantitative molecular imaging in patient care. There are thousands of attendees for its annual meeting, the World Molecular Imaging Congress (WMIC). Two years in a row, our abstract on improving brain tumor surgery by combining MR spectroscopic imaging and 5-ALA intraoperatieve fluorescence-guidance, was selected as a meeting highlihght. In addition, the first author, our MD/PhD student Scott Cordova, was awarded a travel award to present the research results during its annual meeting in Hawaii this year.

Abstract

Glioblastoma (GBM) resection based on T1 contrast-enhanced MRI (T1CE) results in high rates of local recurrence (<2 cm from resection cavity), as infiltrating tumor is known to extend beyond contrast enhancement. Metabolite maps generated from MR spectroscopic imaging (MRSI) are thought to identify high-risk tumor infiltration zones outside of T1CE regions more specifically than T2/FLAIR. As such, coupling preoperative MRSI with real-time fluorescence-guided surgery (FGS) using 5-aminolevulinic acid (5-ALA) may facilitate safe removal of tumor tissue beyond the enhancing tumor margin. One-hundred percent of tissue samples from regions with MRSI abnormalities contained SOX2 positive cells (range: 3 – 96% of total cells). SOX2 positive tumor cells were even found in tissue devoid of T2/FLAIR abnormality. Cho/NAA, Cho/Cr, and tCho values showed strong, statistically significant correlation with the percentage of SOX2-positive tumor cells (Pearson correlation of 0.70, 0.66, and 0.60, respectively, p < 0.05). Intraoperative tumor fluorescence was confirmed ex vivo, and showed less pronounced yet statistically significant correlations with Cho/NAA and  tCho values (0.365 and 0.404, p<0.05). Median EOR in MRSI/5-ALA cases was found to be 97.5% whereas that found in a separate Phase II clinical trial utilizing 5-ALA only was found to be 94.2%. The trend MRSI metabolic abnormalities exhibit with histopathology and quantitative intraoperative fluorescence supports the use of MRSI for identifying regions of tumor infiltration outside of T1CE. MRSI metabolic profiling to allow preoperative prediction of tumor infiltration in terms of percent tumor histology is currently underway. We believe the combination of MRSI-neuronavigation with 5-ALA FGS in this trial will result in more complete resections and prolong both progression-free survival and overall survival.
Scott Cordova

Scott Cordova

MD/PhD Student
Molecular and Systems Pharmacology

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