Abstract 1389: Bismuth gadolinium nanoparticles enhance radiation therapy in hepatocellular carcinoma

Abstract

Abstract Introduction: Primary cancers of the liver is the fourth most common cause of cancer-related deaths and the second most lethal tumor, with a 5-year survival rate of only 18%. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Although HCC is a radiosensitive tumor, radiotherapy (RT) has had a limited role in therapy due to the sensitivity of normal liver parenchyma, thus minimizing radiation exposure is optimal. High atomic number nanoparticles (NP) like bismuth (Bi) and gadolinium (Gd) have been shown to be effective radiosensitizers. Exposure of NP to ionizing radiation leads to the emission of secondary electrons and photons that can damage cells by free radical components, resulting in radiation dose-enhancement. Here we synthesized a multifunctional theranostic NP containing both Bi and Gd (BiGdNP) that can act both as a radiosensitizer and as a bimodal contrast agent for T1 MRI and CT imaging. Materials and Methods: BiGdNP were synthesized using one-pot thermal decomposition of Bi(III) acetate and Gd(III) acetate. Morphology of the NP was characterized by transmission electron microscopy (TEM, JEOL) while Bi and Gd were quantified by inductively coupled plasma-mass spectrometry (ICP-MS, Agilent). Dose-dependent cytotoxicity of BiGdNP was assessed by alamarBlueTM assay. HepG2 cells with BiGdNP were irradiated at 0, 2, and 4 Gy using a 137Cs irradiator. Irradiated cells were incubated at 300 cells/well for 2 weeks. Surviving colonies (1 colony ≥50 cells) were fixed with 10% formalin and stained with 0.5% crystal violet for counting. Magnetic resonance imaging at 4.7 Tesla (Bruker) and micro-computed tomography imaging (GE Medical Systems) were performed on BiGdNP-injected C57BL/6 mice to evaluate liver uptake. Results: Synthesized BiGdNP have good size and shape uniformity with average size of 118 ± 16 nm. No significant difference in cell viability was observed with non-treated and BiGdNP-treated cells at a maximum concentration of 50 μg/mL (p>0.05, t test). This concentration was then used to treat the cells prior to gamma irradiation. In the absence of RT, no adverse effects were observed with BiGdNP-treated cells. For both the 2 and 4 Gy doses, surviving fractions in the BiGdNP-treated groups were decreased than non-treated groups (p<0.05, t test). In addition to radiosensitization, increasing the BiGdNP concentration resulted in increased radiopacity in μ- CT and shorter T1 relaxation time in MRI in vitro and contrast enhancement of the liver in both μ-CT and MRI following intravenous administration in vivo. Conclusion: BiGdNP in combination with RT is more efficient in reducing reproductive viability of HCC than RT alone. The added MRI/CT imaging modality can potentially aid in the visualization of tumor delineation to facilitate localized radiation treatment. Citation Format: Avinash Kakulavar, Raniv D. Rojo, Jossana A. Damasco, Marites P. Melancon, Joy V. Perez. Bismuth gadolinium nanoparticles enhance radiation therapy in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1389.