(131)I-Labeled Copper Sulfide-Loaded Microspheres to Treat Hepatic Tumors via Hepatic Artery Embolization

Purpose: Transcatheter hepatic artery embolization therapy is a minimally invasive alternative for treating inoperable liver cancer but recurrence is frequent. Multifunctional agents, however, offer an opportunity for tumor eradication. In this study, we were aim to synthesized poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating hollow CuS nanoparticles (HCuSNPs) and paclitaxel (PTX) that were then labeled with radioiodine-131 ((131)I) to produce (131)I-HCuSNPs-MS-PTX. This compound combines the multi-theranostic properties of chemotherapy, radiotherapy and photothermal therapy. In addition, it can also be imaged with single photon emission computed tomography (SPECT) imaging and photoacoustic imaging. Methods: We investigated the value of therapeutic and imaging of (131)I-HCuSNPs-MS-PTX in rats bearing Walker-256 tumor transplanted in the liver. After the intra-arterial (IA) injection of (131)I-HCuSNPs-MS-PTX, (18)F-Fluorodeoxyglucose ((18)F-FDG) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging was used to monitor the therapeutic effect. PET/CT findings were verified by immunohistochemical analysis. SPECT/CT and photoacoustic imaging were performed to demonstrate the distribution of (131)I-HCuSNPs-MS-PTX in vivo. Results: We found that embolization therapy in combination with chemotherapy, radiotherapy and photothermal therapy offered by (131)I-HCuSNPs-MS-PTX completely ablated the transplanted hepatic tumors at a relatively low dose. In comparison, embolization monotherapy or combination with one or two other therapies had less effective anti-tumor efficacy. The combination of SPECT/CT and photoacoustic imaging effectively confirmed microsphere delivery to the targeted tumors in vivo and guided the near-infrared laser irradiation. Conclusion: Our study suggests that there is a clinical theranostic potential for imaging-guided arterial embolization with (131)I-HCuSNPs-MS-PTX for the treatment of liver tumors.