The nanometric scale of LNC188Re-SSS could be highly advantageous, as LNCs may penetrate more deeply inside the tumor blood vessels, the mean diameter of microsphere devices are varying between 20 to 500 mm. Moreover, enhanced permeability retention effect, the main strategy for the delivery of nanoparticulate systems, may improve therapeutic efficiency. Indeed, it has been shown that small particles can passively cross the sinusoidal endothelium of the liver through fenestrations with a size of approximately a few hundred nanometers. We report a study of LNC188Re-SSS as a new radiopharmaceutical carrier for internal radiotherapy of rats presenting hepatocellular carcinoma induced by diethylnitrosamine. No early mortality and no intolerance following LNC188Re-SSS intraarterial injection were observed. Our results provide evidences of therapeutic efficiency of LNC188Re-SSS with a reduction in tumor progression which could be combinated with an altered angiogenesis process as indicated by VEGF quantifications in plasmatic samples in a rat HCC model. The use of LNCs, with a structure similar to lipoproteins, could represent a promising therapeutic modality for HCC management, as they modify the biodistribution of entrapped therapeutic agents. These nano-objects include only FDA-approved excipients and are composed of a lipidic core leading to the entrapment of lipophilic molecules such as 188Re-SSS, surrounded by a tension-active shell which induce physicochemical properties different from those of the drug. Additionally, their nanometric scale, and their low polydispersity index but also, the reduced viscosity of the drug, represent real advantages. It could likely avoid the excessive embolization process observed with chemoembolization and may penetrate more deeply inside the tumor blood vessels in comparison with 90Y-microspheres devices. The first step in this study was to demonstrate the relevance of the encapsulation of Rhenium-188 for selective internal radiotherapy on a HCC rat model. The observed liver uptake following LNC188Re-SSS injection and 188Re-perrhenate accumulation in the stomach, which have been already reported in the literature, validate the interest of the encapsulation of Rhenium-188. Organ biodistribution results indicated that LNC188Re-SSS clearance from the blood was mainly ascribed to the liver. The enhancement permeability retention effect may account for these findings. This phenomenon could be explained by the size of LNC188Re-SSS but Ku¨pffer cells could be another explanation for these high throughput screening inquirer observations. In fact, it has been demonstrated that Ku¨pffer cells and some macrophages are involved in nanoparticle capture. Thus, the physicochemical properties of particulate systems improve the liver uptake of Rhenium-188. Hepatotoxicity demonstrated by higher levels of transaminases, could explain its less efficiency in term of survival. Angiogenesis plays a key role in the pathogenesis of many cancers.