title: [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: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu 300, Taiwan.
authors: Ho-Lien
authors: HL
authors: Huang
authors: Chun-Nan
authors: CN
authors: Yeh
authors: Wei-Yuan
authors: WY
authors: Lee
authors: Ying-Cheng
authors: YC
authors: Huang
authors: Kang-Wei
authors: KW
authors: Chang
authors: Kun-Ju
authors: KJ
authors: Lin
authors: Shu-Fan
authors: SF
authors: Tien
authors: Wen-Chin
authors: WC
authors: Su
authors: Ching-Hsiuan
authors: CH
authors: Yang
authors: Jenn-Tzong
authors: JT
authors: Chen
authors: Wuu-Jyh
authors: WJ
authors: Lin
authors: Shio-Shio
authors: SS
authors: Fan
authors: Chung-Shan
authors: CS
authors: Yu
mesh_terms: D000818:Animals; D001681:Biological Assay; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging* / Q000201:enzymology* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D020128:Inhibitory Concentration 50; D008024:Ligands; D008297:Male; D062105:Molecular Docking Simulation; D010654:Phenylbutyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D013379:Substrate Specificity / Q000187:drug effects; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C582781:4-(4'-iodobiphenyl-4-yl)-N-octyl-4-oxobutanamide; D008024:Ligands; D010654:Phenylbutyrates; C010725:fenbufen; D011451:Prostaglandin-Endoperoxide Synthases