Radiotracers for Molecular Imaging of Cyclooxygenase-2 (COX-2) Enzyme

Tietz, Ole; Marshall, Alison; Wuest, Melinda; Wang, M.; Wuest, Frank

doi:10.2174/09298673113206660260

Cited by 36 publications

(33 citation statements)

References 77 publications

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“…Over the past decade, more than two dozen of PET and SPECT radiotracers for COX-2 imaging have been developed. A comprehensive overview of the advances in the field and the challenges surrounding the identification of a suitable radiotracer for COX-2 imaging has been the subject of several recent reviews [ 17 – 19 ]. However, despite the large number of structurally diverse radiolabeled COX-2 inhibitors, most of them based on the celecoxib backbone [ 20 , 21 ], none was suitable for molecular imaging of COX-2 in pre-clinical models of cancer due to lack of sufficient uptake levels in vivo.…”

Section: Introductionmentioning

confidence: 99%

PET imaging of cyclooxygenase-2 (COX-2) in a pre-clinical colorectal cancer model

et al. 2016

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BackgroundCyclooxygenase-2 (COX-2) is the inducible isoform of the cyclooxygenase enzyme family. COX-2 is involved in tumor development and progression, and frequent overexpression of COX-2 in a variety of human cancers has made COX-2 an important drug target for cancer treatment. Non-invasive imaging of COX-2 expression in cancer would be useful for assessing COX-2-mediated effects on chemoprevention and radiosensitization using COX-2 inhibitors as an emerging class of anti-cancer drugs, especially for colorectal cancer. Herein, we describe the radiopharmacological analysis of [18F]Pyricoxib, a novel radiolabeled COX-2 inhibitor, for specific PET imaging of COX-2 in colorectal cancer.MethodsUptake of [18F]Pyricoxib was assessed in human colorectal cancer cell lines HCA-7 (COX-2 positive) and HCT-116 (COX-2 negative). Standard COX-2 inhibitors were used to test for specificity of [18F]Pyricoxib for COX-2 binding in vitro and in vivo. PET imaging, biodistribution, and radiometabolite analyses were included into radiopharmacological evaluation of [18F]Pyricoxib.ResultsRadiotracer uptake in COX-2 positive HCA-7 cells was significantly higher than in COX-2 negative HCT-116 cells (P < 0.05). COX-2 inhibitors, celecoxib, rofecoxib, and SC58125, blocked uptake of [18F]Pyricoxib in HCA-7 cells in a concentration-dependent manner. The radiotracer was slowly metabolized in mice, with approximately 60 % of intact compound after 2 h post-injection. Selective COX-2-mediated tumor uptake of [18F]Pyricoxib in HCA-7 xenografts was confirmed in vivo. Celecoxib (100 mg/kg) selectively blocked tumor uptake by 16 % (PET image analysis; P < 0.05) and by 51 % (biodistribution studies; P < 0.01).ConclusionsThe novel PET radiotracer [18F]Pyricoxib displays a promising radiopharmacological profile to study COX-2 expression in cancer in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0192-9) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

PET imaging of cyclooxygenase-2 (COX-2) in a pre-clinical colorectal cancer model

et al. 2016

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“…Inducible COX-2 and the constitutively expressed COX-1 catalyze the first committed step in the synthesis of PGs, PGE 2 , PGD 2 , PGF 2α , PGI 2 , and TXA 2 [ 68 , 76 , 77 ]. COX-mediated neuronal injury is thought to be due to downstream effects of one or more prostaglandin (PG) products, including PGE 2 , PGD 2 , PGF 2α , PGI 2 and thromboxanes (particularly TXA 2 ) that effect cellular changes through activation of specific prostaglandin receptor subtypes and second messenger systems [ 69 , 76 , 78 ].…”

Section: Introductionmentioning

confidence: 99%

Eryptosis as a marker of Parkinson's disease

Pretorius

Swanepoel

Buys

et al. 2014

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A major trend in recent Parkinson's disease (PD) research is the investigation of biological markers that could help in identifying at-risk individuals or to track disease progression and response to therapies. Central to this is the knowledge that inflammation is a known hallmark of PD and of many other degenerative diseases. In the current work, we focus on inflammatory signalling in PD, using a systems approach that allows us to look at the disease in a more holistic way. We discuss cyclooxygenases, prostaglandins, thromboxanes and also iron in PD. These particular signalling molecules are involved in PD pathophysiology, but are also very important in an aberrant coagulation/hematology system. We present and discuss a hypothesis regarding the possible interaction of these aberrant signalling molecules implicated in PD, and suggest that these molecules may affect the erythrocytes of PD patients. This would be observable as changes in the morphology of the RBCs and of PD patients relative to healthy controls. We then show that the RBCs of PD patients are indeed rather dramatically deranged in their morphology, exhibiting eryptosis (a kind of programmed cell death). This morphological indicator may have useful diagnostic and prognostic significance.

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“…The use of selective COX-2 inhibitors as PET radiotracers for molecular imaging of COX-2 would provide valuable information on tumor prognosis, metastasis, or therapy response. [23][24][25] Up to now, a number of radiotracers basing on clinically used COXIBs like celecoxib and valdecoxib have been described; 26,27 as well as novel compounds with hitherto unknown pharmacological prole were synthesized, radiolabeled and evaluated in vitro and in vivo. 24 Some recent studies with 18 F-labeled pyrazole 28 or azulene 29 based COX-2 inhibitors have successfully demonstrated a specic uptake of radiolabeled COX-2 probes in inammatory lesions as well as in xenograed tumors and gave the proof of principle of targeting COX-2 in vivo with radiotracers.…”

Section: Introductionmentioning

confidence: 99%