Lipiodol Solution Of Re-188-Hdd As A New Therapeutic Agent For Transhepatic Arterial Embolization In Liver Cancer: Preclinical Study In A Rabbit Liver Cancer Model

It has been reported that lipiodol solution of Re-188-labeled 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (TDD), an N2S2 derivative, shows excellent targeting of liver cancer after transhepatic arterial embolization (TAE). However, its tumor retention is not high enough to treat liver cancer. Therefore, a new form of TDD, 4-hexadecyl-TDD (HDD), was developed to improve tumor retention by introducing a long alkyl chain. In this study, we compared the tumor retention properties of Re-188-HDD/lipiodol and Re-188-TDD/lipiodol, using a rabbit liver cancer model, and performed dosimetry using the results. Methods: The VX2 cancer cell line was implanted into the livers of 7 rabbits. TAE was performed on 3 rabbits with Re-188-TDD/lipiodol and on 4 rabbits with Re-188-HDD/lipiodol, and conjugated anterior and posterior planar scans were obtained at 1, 2, 6, 24, and 48 h after TAE. From these images, tumor retention was calculated and compared between Re-188-TDD and Re-188-HDD. Afterward, the required dose of radioactivity and the radiation dosimetry for exposure of major organs were calculated using MIRDOSE3.1 software. Results: The residence times of radioactivity in the liver were 10.2 +/- 1.0 h in the Re-188-TDD group and 17.6 +/- 0.8 h in the Re-188-HDD group (P = 0.034). The required radioactivity for 100 Gy of irradiation to 2.64- to 5.27-cm tumors was 142-1,070 MBq of Re-188-HDD in the rabbit model. The radiation exposures for the major organs were within the tolerable range, and the S-value for the whole body (effective dose equivalent) was calculated to be 0.209 mSv/MBq. Conclusion: Introduction of a long alkyl chain significantly improved the tumor retention of Re-188-HDD/lipiodol, compared with that of Re-188-TDD/lipiodol. Moreover, the required radioactivity for humans and the radiation exposure were within the feasible range for clinical application.