title: 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.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jin Chul
authors.initials: JC
authors.lastname: Paeng
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Chang Jin
authors.initials: CJ
authors.lastname: Yoon
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Young-Ger
authors.initials: YG
authors.lastname: Suh
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Chung
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Miwon
authors.initials: M
authors.lastname: Son
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Lee
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004621:Embolization, Therapeutic; D006801:Humans; D007459:Iodized Oil / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy*; D008657:Metabolic Clearance Rate; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011817:Rabbits; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*
chemical_list: C431271:188Re 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol; C482310:188Re 4-hexadecy-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D007459:Iodized Oil