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.

Abstract

INTRODUCTION:

A lipiodol solution of (188)Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (HTDD) has been successfully developed for liver cancer therapy; however, its preparation requires a multi-step synthesis and it is characterized by a low labeling yield.

METHODS:

We synthesized a new compound, 4-hexadecyl-4,7-diaza-1,10-decanedithioacetate (AHDD), without gem dimethyl groups to address these issues. AHDD was formulated into a kit and was labeled with (188)Re. Biodistribution study was performed using normal BALB/c mice.

RESULTS:

The kit was labeled with (188)Re with a high efficiency (98.8±0.2%). After extraction with lipiodol, the overall yield of (188)Re-HDD/lipiodol was as high as 90.2±2.6%. A comparative biodistribution study of (188)Re-HTDD and (188)Re-HDD was performed in normal mice after intravenous injection. The lungs were identified as the main uptake site due to capillary-blockage. (188)Re-HDD/lipiodol showed a significantly higher lung uptake than that of (188)Re-HTDD/lipiodol (p<0.05).

CONCLUSION:

The newly synthesized (188)Re-HDD/lipiodol showed improved radiolabeling yield and biodistribution results compared to (188)Re-HTDD/lipiodol, and may therefore be more suitable for liver cancer therapy.

• Authors: Vinay Kumar Banka, Sung-Hyun Moon, Jae Min Jeong, Sudhakara Reddy Seelam, Yun-Sang Lee, Young Joo Kim, Dong Soo Lee, June-Key Chung
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 42 Issue 3 Pg. 317-22 (Mar 2015) ISSN: 1872-9614 [Electronic] United States
• PMID: 25537725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• 188Re 4-hexadecy-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol
• Coordination Complexes
• Organometallic Compounds
• Radioisotopes
• Cysteamine
• Rhenium
• Ethiodized Oil

Topics

• Animals
• Chemistry Techniques, Synthetic
• Chemistry, Pharmaceutical
• Coordination Complexes (chemical synthesis, chemistry, pharmacokinetics, therapeutic use)
• Cysteamine (analogs & derivatives, chemical synthesis, chemistry, pharmacokinetics, therapeutic use)
• Drug Compounding
• Drug Design
• Embolization, Therapeutic
• Ethiodized Oil (chemistry)
• Liver Neoplasms (therapy)
• Mice
• Mice, Inbred BALB C
• Organometallic Compounds
• Radiochemistry
• Radioisotopes (therapeutic use)
• Rhenium (therapeutic use)
• Tissue Distribution