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.


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.
Paeng
Jin Chul
JC
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jeong
Jae Min
JM
Yoon
Chang Jin
CJ
Lee
Yun-Sang
YS
Suh
Young-Ger
YG
Chung
Jin Wook
JW
Park
Jae Hyung
JH
Chung
June-Key
JK
Son
Miwon
M
Lee
Myung Chul
MC
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*
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