Development of acetylated HDD kit for preparation of ¹⁸⁸Re-HDD/lipiodol

Abstract

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Objectives: It was reported that lipiodol solution of ¹⁸⁸Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (HDD) accumulates effectively in the liver cancer when injected through the hepatic artery. However, formulation of the HDD kit has difficulties due to the high reactivity of sulfhydryl groups of HDD. We produced new kits using diacetylated HDD (AHDD), in which sulfhydryl groups of HDD are protected with acetyl groups for increasing stability, and established the preparation of lipiodol solution of ¹⁸⁸Re-HDD from AHDD kit.

Methods: Freeze-dried kits containing AHDD, tartaric acid, SnCl₂×2H₂O and mannitol were produced. The kits were labeled with ¹⁸⁸Re-perrhenate (37-590 MBq/3-6 ml) with various pH conditions in boiling water. Final pH was adjusted using an adequate amount of 0.43 M trisodium phosphate solution. Biodistribution of each ¹⁸⁸Re-HDD/lipiodol solution either from AHDD kit or from HDD kit was also compared in mice. ¹⁸⁸Re-HDD was extracted with lipiodol (3 ml). Each ¹⁸⁸Re-HDD/lipiodol solution from AHDD kit and HDD kit (370 kBq/0.03 ml) was injected into male ICR mice (25.3 ± 1.1 g, n = 3~4/group) through the tail vein. Biodistribution data were obtained after 30 min, 1, 3 and 24 hr.

Results: The ¹⁸⁸Re labeling yields of AHDD kits with various volume of ¹⁸⁸Re-perrhenate were 50~76%. The maximum yield of ¹⁸⁸Re labeling and extraction was found at pH 3.5. Combination of reaction at pH 1.4 and extraction at pH 6.8 showed the highest yield 78%. 5~8% of the radioactivity remained in the vial. Both two preparations from HDD kit and AHDD kit showed no significantly different lung uptake after intravenous injection into mice.

Conclusions: We prepared AHDD kit and established the optimal condition for preparation of ¹⁸⁸Re-HDD/lipiodol. AHDD kit would be an excellent replacement for preparation of ¹⁸⁸Re-HDD/lipiodol, which would overcome the problem of HDD for formulation.