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

Huang, Ho-Lien, Yeh, Chun-Nan, Lee, Wei-Yuan, Huang, Ying-Cheng, Chang, Kang-Wei, Lin, Kun-Ju, Tien, Shu-Fan, Su, Wen-Chin, Yang, Ching-Hsiuan, Chen, Jenn-Tzong, Lin, Wuu-Jyh, Fan, Shio-Shio, Yu, Chung-Shan
Biomaterials 2013 v.34 no.13 pp. 3355-3365
bile ducts, computed tomography, enzymes, gel chromatography, high performance liquid chromatography, image analysis, inflammation, inhibitory concentration 50, liver, neoplasms, rats
This study is concerned with the development of an agent for single photon emission computer tomography (SPECT) for imaging inflammation and tumor progression. [¹²³I]Iodooctyl fenbufen amide ([¹²³I]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 [¹²³I]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 IC₅₀ value compared to fenbufen. In the normal rat liver, a lower level and homogeneous pattern of [¹²³I]IOFA radioactivity was observed by SPECT. In contrast, in the rat liver with thioacetamide-induced cholangiocarcinoma, a higher uptake and heterogeneous pattern of [¹²³I]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, [¹²³I]IOFA was found to exhibit the potential for imaging tumors that over-express COX.