Lipiodol-Mediated Dose Enhancement in Radiation Therapy: A Phantom and In Vitro Study in Hepatocellular Carcinoma.

[PURPOSE] To assess Lipiodol-mediated photon dose perturbation and biological effects using complementary kilovoltage and megavoltage irradiation geometries relevant to hepatocellular carcinoma.

[MATERIALS AND METHODS] Phantom dosimetry used containers filled with lipiodol-oil mixtures (0-100%) embedded in a water phantom with radiochromic film to quantify concentration-dependent enhancement under 6-MV beam. HepG2 human hepatoma cells were irradiated at 0-6 Gy using 160-kVp (photoelectric effect dominant) with lipiodol or water placed beneath the cell monolayer to isolate backscatter; γH2AX foci indicating DNA damage were quantified shortly after irradiation. For megavoltage testing, a 6-MV (Compton scattering dominant) Lipiodol-rich "sandwich" geometry (Lipiodol above and below the cell monolayer) was used; apoptosis was quantified at 96 h using NucView/NucSpot (apoptotic fraction), and results are reported descriptively.

[RESULTS] Film dosimetry demonstrated increasing enhancement with Lipiodol concentration, spatially localized to the Lipiodol region, with a maximum localized increase of 57.1% at 100% Lipiodol versus water. In the 160-kVp backscatter model, higher γH2AX foci were observed at 4 and 6 Gy in Lipiodol versus control. In the 6-MV sandwich model, cell-plane film confirmed an 11.5% higher delivered dose at 2 Gy with Lipiodol and apoptotic fraction was 1.36-5.79-fold higher across 2-6 Gy compared to the control.

[CONCLUSION] Lipiodol measurably intensified local photon dose and was associated with greater DNA damage and apoptosis in phantom and HepG2 cell models. These findings provide mechanistic support for combining radiotherapy with Lipiodol-based transarterial treatments and highlight the need for further in vivo validation and clinical studies.