Purpose: Thermochemical ablation (TCA) is a minimally invasive therapy under development for hepatocellular carcinoma. TCA utilizes acid/base chemistry delivered simultaneously directly into the tumor to induce local ablation when administered. When delivered via a mixing catheter, acid (AcOH) and base (NaOH) react to completion at the catheter tip before delivery into tumor, producing the acetate salt, water, and releasing heat (Δ>50°C) in sufficient quantities to induce lethal osmotic and thermal stress in tumor cells. However, these two reagents are not distinguishable from tissues, which makes monitoring delivery of TCA difficult. We address this issue by developing CsOH as a novel theranostic component of TCA that is detectable with CT.
Methods: VX2 tumor fragments (0.3mL) from carrier animals were inoculated into the flank of New Zealand white rabbits and allowed to grow for 10 days until tumor diameter reached 1-2cm. Catheters were placed under ultrasound guidance and TCA was delivered as 5M AcOH and 5M NaOH doped with 250mM CsOH. Concentration selection was informed by previous studies.A split-filter DECT system (Definition Edge, Siemens Healthineers) was used to acquire images pre-and post-TCA treatment with the following parameters:120kVp, Au/Sn filter, and CTDIvol=1.39mGy. 20mm line profiles were drawn on 70keV monoenergetic images (Syngo.via) through the ablation center (ImageJ, NIH). Cesium concentration was quantified using the HU and CsOH concentration relationship (R2=0.999) determined in previous studies.
Results: The resulting line profile has a maximum CT number of 692HU (220mM) near the center of the injection site and decreases to approximately 40HU (12mM) at the periphery of the ablated region, demonstrating higher cesium concentration near the center, decreased concentration at the periphery, and none beyond the ablation zone.
Conclusion: DECT is a viable technique for quantitative monitoring to monitor tumor ablation when CsOH is incorporated as a theranostic agent in image-guided TCA interventions.
Funding Support, Disclosures, and Conflict of Interest: Emily Thompson was supported by the CPRIT Research Training Grant (RP170067) and the SIR Foundation Allied Scientist Training Grant.