Universität zu Köln

Morgenroth, Agnieszka, Vogg, Andreas T. J., Neumaier, Bernd ORCID: 0000-0001-5425-3116, Mottaghy, Felix M. and Zlatopolskiy, Boris D. (2017). Radioiodinated indomethacin amide for molecular imaging of cyclooxygenase-2 expressing tumors. Oncotarget, 8 (11). S. 18059 - 18070. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Morgenroth, Agnieszka UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogg, Andreas T. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumaier, Bernd UNSPECIFIED orcid.org/0000-0001-5425-3116 UNSPECIFIED Mottaghy, Felix M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zlatopolskiy, Boris D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236634
DOI:	10.18632/oncotarget.15437
Journal or Publication Title:	Oncotarget
Volume:	8
Number:	11
Page Range:	S. 18059 - 18070
Date:	2017
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SELECTIVE-INHIBITION; COX-2 INHIBITORS; IN-VIVO; AGENTS; DESIGN; CANCER; INFLAMMATION; SYSTEM; MOUSE Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23663