Application of Trifluoroacetic Acid as a Theranostic Agent for Chemical Ablation of Solid Tissue

To evaluate trifluoroacetic acid (TFA) as a theranostic chemical ablation agent and determine the efficacy of TFA for both noninvasive imaging and tissue destruction.

Fluorine-19 magnetic resonance imaging (¹⁹F-MRI) was optimized at 7 T using a custom-built volume coil. Fluorine images were acquired with both rapid acquisition with relaxation enhancement and balanced steady-state free precession (bSSFP) sequences with varying parameters to determine the optimal sequence for TFA. The theranostic efficacy of chemical ablation was examined by injecting TFA (100 μL; 0.25, 0.5, 1.0, and 2.0M) into ex vivo porcine liver. ¹⁹F and proton MRI were acquired and superimposed to visualize distribution of TFA in tissue and quantify sensitivity. Tissue damage was evaluated with gross examination, histology, and fluorescence microscopy.

The optimal ¹⁹F-MRI sequence was found to be bSSFP with a repetition time of 2.5 ms and flip angle of 70°. The minimum imageable TFA concentration was determined to be 6.7 ± 0.5 mM per minute of scan time (0.63×0.63×5.00 mm voxel), and real-time imaging (temporal resolution of at least 1 s^-1) was achieved with 2M TFA both in vitro and in ex vivo tissue. TFA successfully coagulated tissue, and damage was locally confined. In addition to hepatic cord disruption, cytoskeletal collapse and chromatin clumping were observed in severely damaged areas in tissues treated with 0.5M or higher TFA concentrations.

TFA was determined to be a theranostic agent for chemical ablation of solid tissue. Ablation was both efficacious and imageable in ex vivo healthy tissue, even at low concentrations or with high temporal resolution.