Synthesis of 188Re-labelled long chain alkyl diaminedithiol for therapy of liver cancer

Abstract

Radioisotope-labelled lipiodol has been used in the therapy of liver cancer. Recently a lipiodol solution of 188Re-labelled diaminedithiol (DD) has been reported to show a high uptake in the liver cancer. We synthesized long-chain alkyl DD derivatives to improve their uptake and retention in tissue. As the length of the alkyl chain increased, tissue uptake and retention also increased due to hydrophobic interaction with lipiodol. Among the synthesized compounds, the lipiodol solution of 188Re-HDD, the DD derivative with the longest side chain (C16), is a promising agent for therapy of liver cancer.

Development of 4-hexadecyl-4,7-diaza-1,10-decanedithiol (HDD) kit for the preparation of the liver cancer therapeutic agent Re-188-HDD/lipiodol

“…As expected, the lungs showed the highest uptake in both the 188 Re-HDD and 188 Re-HTDD among the organs evaluated due to capillary embolism [7,20,24] (Fig. 2).…”

“…AHDD and AHTDD kits were prepared for radiolabeling with 188 Re according to a previously published method [20]. The kits were prepared by freeze drying in 10-mL vials containing 1 mg of AHDD or AHTDD, 6 mg of SnCl 2 · 2H 2 O, 20 mg of tartaric acid, and 10 mg of mannitol.…”

“…188 Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (HTDD)/lipiodol was later developed to address these limitations; owing to its high labeling yield and simple preparation, 188 Re-HTDD/lipiodol was successfully introduced for clinical application [6,7,20]. Multi-center clinical application of 188 Re-HTDD/lipiodol was initiated by the International Atomic Energy Agency (IAEA) [21][22][23].…”

Radiolabeled Lipiodol Therapy for Hepatocellular Carcinoma in Patients Awaiting Liver Transplantation: Pathology of the Explant Livers and Clinical Outcome

“…Lyophilized kits containing a HDDchelator (4-hexadecyl-1-2, 9, 9-tetramethyl-4, 7-diaza-1,10-decanethiol) were provided by the Seoul National University Hospital (Seoul, Korea) and 188 ReHDD/lipiodol was synthesized, as described earlier by Lee et al 13 After selective hepatic catheterization, a mean activity of 2.1 GBq 131 I or 4.1 GBq 188 Re in a total volume of 2-4 mL of lipiodol was instilled in the proper hepatic artery or in its right and/or left branches.…”

A kit formulation for the labelling of lipiodol with generator‐produced 188Re

“…13 Re-complex into cold lipiodol, as a consequence of the strong hydrophobic interaction between the lipophilic metal complex and the fatty oil. [10][11][12]15,16 This second approach, easier to perform, seems to be the most promising. However, the methods described lack a satisfactory yield and reproducibility.…”