Abstract Background Radioembolization is one therapeutic option for the treatment of locally early-stage hepatocellular carcinoma. The aim of this study was to evaluate the distribution of Lipiodol® ultra-fluid and microspheres and to simulate their effectiveness with different beta emitters (⁹⁰Y, ¹⁸⁸Re, ³²P, ¹⁶⁶Ho, ¹³¹I, and ¹⁷⁷Lu) on VX2 tumors implanted in the liver of 30 New Zealand rabbits. Results Twenty-three out of 30 rabbits had exploitable data: 14 in the group that received Lipiodol® ultra-fluid (group L), 6 in the group that received microspheres (group M), and 3 in the control group (group C). The histologic analysis showed that the Lipiodol® ultra-fluid distributes homogeneously in the tumor up to 12 days after injection. The X-ray μCT images showed that Lipiodol® ultra-fluid has a more distal penetration in the tumor than microspheres. The entropy (disorder of the system) in the L group was significantly higher than in the M group (4.06 vs 2.67, p = 0.01). Equivalent uniform biological effective doses (EUBED) for a tumor-absorbed dose of 100 Gy were greater in the L group but without statistical significance except for ¹⁷⁷Lu (p = 0.03). The radionuclides ranking by EUBED (from high to low) was ⁹⁰Y, ¹⁸⁸Re, ³²P, ¹⁶⁶Ho, ¹³¹I, and ¹⁷⁷Lu. Conclusions This study showed a higher ability of Lipiodol® ultra-fluid to penetrate the tumor that translated into a higher EUBED. This study confirms ⁹⁰Y as a good candidate for radioembolization, although ³²P, ¹⁶⁶Ho, and ¹⁸⁸Re can achieve similar results.