Radioiodinated indomethacin amide for molecular imaging of cyclooxygenase-2 expressing tumors
Metrics: PDF 1003 views | HTML 1145 views | ?
Agnieszka Morgenroth1, Andreas T.J. Vogg1, Bernd Neumaier2,3,4, Felix M. Mottaghy1,5, Boris D. Zlatopolskiy1,2,3
1Department for Nuclear Medicine, RWTH Aachen University Hospital, 52074, Aachen, Germany
2Institute of Radiochemistry and Experimental Molecular Imaging, University Clinic Cologne, 50937, Cologne, Germany
3Max Planck Institute of Metabolism Research, 50931, Cologne, Germany
4Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Research Center Jülich, 52425, Jülich, Germany
5Department of Nuclear Medicine, Maastricht University Medical Center, 6229 HX, Maastricht, The Netherlands
Agnieszka Morgenroth, email: email@example.com
Keywords: cyclooxygenase-2, colorectal carcinoma, indomethacin, celecoxib, PET imaging
Received: July 26, 2016 Accepted: January 27, 2017 Published: February 17, 2017
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.