[123I]Iodooctyl fenbufen amide as a SPECT tracer for imaging tumors that over-express COX enzymes.

Abstract

This study is concerned with the development of an agent for single photon emission computer tomography (SPECT) for imaging inflammation and tumor progression. [(123)I]Iodooctyl fenbufen amide ([(123)I]IOFA) was prepared from the precursor N-octyl-4-oxo-4-(4'-(trimethylstannyl)biphenyl-4-yl)butanamide with a radiochemical yield of 15%, specific activity of 37 GBq/μmol, and radiochemical purity of 95%. Analysis of the binding of [(123)I]IOFA to COX-1 and COX-2 enzymes by using HPLC and a gel filtration column showed a selectivity ratio of 1:1.3. An assay for the competitive inhibition of substrate transfer showed that IOFA exhibited a comparable IC(50) value compared to fenbufen. In the normal rat liver, a lower level and homogeneous pattern of [(123)I]IOFA radioactivity was observed by SPECT. In contrast, in the rat liver with thioacetamide-induced cholangiocarcinoma, a higher uptake and heterogeneous pattern of [(123)I]IOFA radioactivity was seen as hot spots in tumor lesions by SPECT imaging. Importantly, elevated COX-1 and COX-2 expressions from immunostaining were found in the bile ducts of tumor rats but not of normal rats. Therefore, [(123)I]IOFA was found to exhibit the potential for imaging tumors that over-express COX.

• Authors: Ho-Lien Huang, Chun-Nan Yeh, Wei-Yuan Lee, Ying-Cheng Huang, Kang-Wei Chang, Kun-Ju Lin, Shu-Fan Tien, Wen-Chin Su, Ching-Hsiuan Yang, Jenn-Tzong Chen, Wuu-Jyh Lin, Shio-Shio Fan, Chung-Shan Yu
• Journal: Biomaterials (Biomaterials) Vol. 34 Issue 13 Pg. 3355-65 (Apr 2013) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 23384791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• 4-(4'-iodobiphenyl-4-yl)-N-octyl-4-oxobutanamide
• Ligands
• Phenylbutyrates
• fenbufen
• Prostaglandin-Endoperoxide Synthases

Topics

• Animals
• Biological Assay
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cholangiocarcinoma (diagnostic imaging, enzymology, pathology)
• Chromatography, High Pressure Liquid
• Inhibitory Concentration 50
• Ligands
• Male
• Molecular Docking Simulation
• Phenylbutyrates (chemical synthesis, chemistry, pharmacology)
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sheep
• Substrate Specificity (drug effects)
• Tomography, Emission-Computed, Single-Photon