Research Papers:

Radioiodinated indomethacin amide for molecular imaging of cyclooxygenase-2 expressing tumors

Agnieszka Morgenroth _, Andreas T.J. Vogg, Bernd Neumaier, Felix M. Mottaghy and Boris D. Zlatopolskiy

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Oncotarget. 2017; 8:18059-18069. https://doi.org/10.18632/oncotarget.15437

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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

Correspondence to:

Agnieszka Morgenroth, email: [email protected]

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.

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