Abstract

INTRODUCTION
Hepatocellular carcinoma is the most common form of primary hepatic carcinoma. A new N(2)S(2) tetradentate ligand, N-[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3-[2-(triphenylmethyl)thioethyl]octadecanoate (H(3)MN-16ET), was introduced and labeled with (188)Re to create (188)Re-MN-16ET in the Lipiodol phase. The potential of (188)Re-MN-16ET/Lipiodol for hepatoma therapy was evaluated in a hepatocellular carcinoma animal model of Sprague-Dawley rats implanted with the N1S1 cell line.
METHODS
Synthesis of H(3)MN-16ET was described, and characterization was identified by infrared, nuclear magnetic resonance and mass spectra. We compared the effects of transchelating agents (glucoheptonate or tartaric acid) and a reducing agent (stannous chloride) on the complexing of (188)Re-perrhenate and H(3)MN-16ET. Twenty-four rats implanted with hepatoma were injected with 3.7 MBq/0.1 ml of (188)Re-MN-16ET/Lipiodol or (188)Re-MN-16ET via transcatheter arterial embolization. Biodistribution experiments and single-photon emission computed tomography imaging were performed to investigate tumor accumulation.
RESULTS
H(3)MN-16ET was proved to easily conjugate with the Re isotope and showed good solubility in Lipiodol. The radiochemical purity of (188)Re-MN-16ET/Lipiodol with 10 mg tartaric acid and stannous chloride was shown to be more than 90%. The major distribution sites of (188)Re-MN-16ET in Sprague-Dawley rats were hepatoma and the liver. However, the radioactivity at the tumor site postadministered with (188)Re-MN-16ET was quickly decreased from 9.15±0.23 (at 1 h) to 2.71%±0.18% of injected dose/g (at 48 h). The biodistribution and micro-single-photon emission computed tomography/computed tomography image data showed that (188)Re-MN-16ET/Lipiodol was selectively retained at the tumor site, with 11.55±1.44, 13.16±1.46 and 10.67%±0.95% of injected dose/g at 1, 24 and 48 h postinjection, respectively. The radioactivity in normal liver tissue was high but significantly lower than that of the tumors.
CONCLUSION
H(3)MN-16ET is a suitable tetradentate ligand for (188)Re labeling. From the animal data, we suggest that (188)Re-MN-16ET/Lipiodol has the potential to be a therapeutic radiopharmaceutical for hepatoma treatment.

Links

Publisher Full Text

Authors

Tang IC, Luo TY, Liu SW, Chan SH, Kung HC, Peng CL, Lin WY, Chang Y, Lin WJ

Institution

Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546.

Source

Nuclear medicine and biology 38:7 2011 Oct pg 1043-52

MeSH

Animals
Carcinoma, Hepatocellular
Cell Line, Tumor
Coordination Complexes
Disease Models, Animal
Ethiodized Oil
Glycine
Liver Neoplasms
Male
Palmitic Acids
Radiochemistry
Radioisotopes
Rats
Rhenium
Stearates
Tomography, Emission-Computed, Single-Photon

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21831647