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• W2589300908 abstract "// Agnieszka Morgenroth 1 , Andreas T.J. Vogg 1 , Bernd Neumaier 2, 3, 4 , Felix M. Mottaghy 1, 5 , Boris D. Zlatopolskiy 1, 2, 3 1 Department for Nuclear Medicine, RWTH Aachen University Hospital, 52074, Aachen, Germany 2 Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, 50937, Cologne, Germany 3 Max Planck Institute of Metabolism Research, 50931, Cologne, Germany 4 Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Research Center Jülich, 52425, Jülich, Germany 5 Department of Nuclear Medicine, Maastricht University Medical Center, 6229 HX, Maastricht, The Netherlands Correspondence to: Agnieszka Morgenroth, email: amorgenroth@ukaachen.de Keywords: cyclooxygenase-2, colorectal carcinoma, indomethacin, celecoxib, PET imaging Received: July 26, 2016      Accepted: January 27, 2017      Published: February 17, 2017 ABSTRACT Cyclooxygenase-2 (COX-2) is an important biomarker in several tumors. Available imaging probes display relatively low tumor to background ratios (smaller than 2:1). We evaluated newly developed indomethacin (Ind) derivatives for in vivo molecular imaging of COX-2 expressing carcinoma. Radioiodinated Ind derivatives Ind-NH-(CH2)4-NH-3-[I-125]I-Bz ([I-125]5), Ind-NH-(CH2)4-NH-5-[I-124/125]I-Nic ([I-124/125]6) and Ind-NH-(CH2)4-NH-5-[I-125]I-Iphth ([I-125]7) were prepared from the respective SnBu3-precursors (45–80% radiochemical yield; > 95% radiochemical purity). The cellular uptake of [I-125]5 and [I-125]6 correlated with COX-2 expression determined by SDS page/Western blot analysis. [I-125]5 was predominantly localized in the cell membrane while [I-125]6 was internalized and displayed a diffuse and favorable cytoplasmic distribution. In contrast, [I-125]7 showed only low uptake in COX-2 positive cells. Co-incubation with the COX-2 inhibitor Celecoxib led to an almost complete suppression of cellular uptake of [I-125]5 and [I-125]6. In vivo molecular imaging using positron emission tomography (PET) in SCID mice xenografted with COX-2 + (HT29) and COX-2 − (HCT116) human colorectal carcinoma cells was performed for [I-124]6. HT29 xenografts displayed a significantly higher uptake than HCT-116 xenografts (5.6 ± 1.5 vs. 0.5 ± 0.1 kBq/g, P < 0.05) with an extraordinary high tumor to muscle ratio (50.3 ± 1.5). Immunohistological staining correlated with the imaging data. In conclusion, the novel radioiodinated indomethacin derivative ([I-124/125]6) could become a valuable tool for development of molecular imaging probes for visualization of COX-2 expressing tumors." @default.
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• W2589300908 date "2017-02-17" @default.
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• W2589300908 title "Radioiodinated indomethacin amide for molecular imaging of cyclooxygenase-2 expressing tumors" @default.
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