¹⁸F-FDG PET Biomarkers Help Detect Early Metabolic Response to Irreversible Electroporation and Predict Therapeutic Outcomes in a Rat Liver Tumor Model.

Abstract

Purpose To test the hypothesis that biomarkers of fluorine 18 (¹⁸F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUV_max) was calculated 3 days after IRE. The maximum lesion diameter change (ΔD_max) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUV_max and ΔD_max were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUV_max at 3 days and ΔD_max (or apoptosis index) at 14 days after IRE treatment. Results ΔSUV_max, ΔD_max, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUV_max 3 days after IRE and ΔD_max 14 days after IRE (R = 0.66, P = .01) and between ΔSUV_max 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion ¹⁸F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model. ^© RSNA, 2017.