Lipiodol solution of 188Re-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 (188)Re-labeled 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (TDD), an N(2)S(2) 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 (188)Re-HDD/lipiodol and (188)Re-TDD/lipiodol, using a rabbit liver cancer model, and performed dosimetry using the results.
The VX2 cancer cell line was implanted into the livers of 7 rabbits. TAE was performed on 3 rabbits with (188)Re-TDD/lipiodol and on 4 rabbits with (188)Re-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 (188)Re-TDD and (188)Re-HDD. Afterward, the required dose of radioactivity and the radiation dosimetry for exposure of major organs were calculated using MIRDOSE3.1 software.
The residence times of radioactivity in the liver were 10.2 +/- 1.0 h in the (188)Re-TDD group and 17.6 +/- 0.8 h in the (188)Re-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 (188)Re-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.
Introduction of a long alkyl chain significantly improved the tumor retention of (188)Re-HDD/lipiodol, compared with that of (188)Re-TDD/lipiodol. Moreover, the required radioactivity for humans and the radiation exposure were within the feasible range for clinical application.
AuthorsJin Chul Paeng, Jae Min Jeong, Chang Jin Yoon, Yun-Sang Lee, Young-Ger Suh, Jin Wook Chung, Jae Hyung Park, June-Key Chung, Miwon Son, Myung Chul Lee
JournalJournal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 44 Issue 12 Pg. 2033-8 (Dec 2003) ISSN: 0161-5505 [Print] United States
PMID14660730 (Publication Type: Comparative Study, Evaluation Studies, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 188Re 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol
  • 188Re 4-hexadecy-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Iodized Oil
  • Animals
  • Carcinoma, Squamous Cell (metabolism, radiotherapy, therapy)
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Embolization, Therapeutic
  • Humans
  • Iodized Oil (pharmacokinetics)
  • Liver Neoplasms (metabolism, radiotherapy, therapy)
  • Metabolic Clearance Rate
  • Neoplasm Transplantation
  • Organometallic Compounds (pharmacokinetics, therapeutic use)
  • Rabbits
  • Radiation Dosage
  • Radiometry (methods)
  • Radiopharmaceuticals (pharmacokinetics, therapeutic use)
  • Radiotherapy Planning, Computer-Assisted (methods)

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