PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neuroinflammation and first-in-human study.

التفاصيل البيبلوغرافية
العنوان:	PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neuroinflammation and first-in-human study.
المؤلفون:	Shrestha S; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Medical Scientist Training Program, University of Miami Miller School of Medicine, Miami, FL, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Kim MJ; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA. minjeong.kim@nih.gov.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA. minjeong.kim@nih.gov., Eldridge M; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA., Lehmann ML; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA., Frankland M; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Liow JS; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Yu ZX; National Heart, Lung, and Blood Institute Intramural Research Program, Bethesda, MD, USA., Cortes-Salva M; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Telu S; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Henter ID; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Gallagher E; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Lee JH; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Fredericks JM; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA., Poffenberger C; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA., Tye G; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Ruiz-Perdomo Y; National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA., Anaya FJ; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Montero Santamaria JA; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Gladding RL; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Zoghbi SS; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Fujita M; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Katz JD; National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, USA., Pike VW; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA., Innis RB; National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA.; Molecular Imaging Branch, National Institute of Mental Health, 10 Center Drive, Bldg. 10, Rm B1D43, Bethesda, MD, 20892-1026, USA.
المصدر:	Journal of neuroinflammation [J Neuroinflammation] 2020 May 02; Vol. 17 (1), pp. 140. Date of Electronic Publication: 2020 May 02.
نوع المنشور:	Clinical Trial; Journal Article
اللغة:	English
بيانات الدورية:	Publisher: BioMed Central Country of Publication: England NLM ID: 101222974 Publication Model: Electronic Cited Medium: Internet ISSN: 1742-2094 (Electronic) Linking ISSN: 17422094 NLM ISO Abbreviation: J Neuroinflammation Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: [London] : BioMed Central, c2004-
مواضيع طبية MeSH:	Pyrimidines* , Radiopharmaceuticals, Cyclooxygenase 2/analysis , Inflammation/diagnostic imaging , Positron-Emission Tomography/methods, Adult ; Animals ; Arthritis, Rheumatoid/diagnostic imaging ; Brain/diagnostic imaging ; Female ; Humans ; Macaca mulatta ; Middle Aged
مستخلص:	Background: Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing inflammatory response in the brain and periphery. To date, however, the development of PET radioligands for COX-2 has had limited success. Methods: The novel PET tracer [ ¹¹ C]MC1 was used to examine COX-2 expression [1] in the brains of four rhesus macaques at baseline and after injection of the inflammogen lipopolysaccharide (LPS) into the right putamen, and [2] in the joints of two human participants with rheumatoid arthritis and two healthy individuals. In the primate study, two monkeys had one LPS injection, and two monkeys had a second injection 33 and 44 days, respectively, after the first LPS injection. As a comparator, COX-1 expression was measured using [ ¹¹ C]PS13. Results: COX-2 binding, expressed as the ratio of specific to nondisplaceable uptake (BP ND ) of [ ¹¹ C]MC1, increased on day 1 post-LPS injection; no such increase in COX-1 expression, measured using [ ¹¹ C]PS13, was observed. The day after the second LPS injection, a brain lesion (~ 0.5 cm in diameter) with high COX-2 density and high BP ND (1.8) was observed. Postmortem brain analysis at the gene transcript or protein level confirmed in vivo PET results. An incidental finding in an unrelated monkey found a line of COX-2 positivity along an incision in skull muscle, demonstrating that [ ¹¹ C]MC1 can localize inflammation peripheral to the brain. In patients with rheumatoid arthritis, [ ¹¹ C]MC1 successfully imaged upregulated COX-2 in the arthritic hand and shoulder and apparently in the brain. Uptake was blocked by celecoxib, a COX-2 preferential inhibitor. Conclusions: Taken together, these results indicate that [ ¹¹ C]MC1 can image and quantify COX-2 upregulation in both monkey brain after LPS-induced neuroinflammation and in human peripheral tissue with inflammation. Trial Registration: ClinicalTrials.gov NCT03912428. Registered April 11, 2019.
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معلومات مُعتمدة:	T32 GM112601 United States GM NIGMS NIH HHS; ZIAMH002793 United States AR NIAMS NIH HHS; ZIAMH002795 United States MH NIMH NIH HHS
فهرسة مساهمة:	Keywords: Cyclooxygenase 1; Cyclooxygenase 2; Inflammation; Lipopolysaccharide; Positron emission tomography; Rheumatoid arthritis
سلسلة جزيئية:	ClinicalTrials.gov NCT03912428
المشرفين على المادة:	0 ((11C)-MC1) 0 (Pyrimidines) 0 (Radiopharmaceuticals) EC 1.14.99.1 (Cyclooxygenase 2)
تواريخ الأحداث:	Date Created: 20200504 Date Completed: 20210319 Latest Revision: 20210319
رمز التحديث:	20221213
مُعرف محوري في PubMed:	PMC7195739
DOI:	10.1186/s12974-020-01804-6
PMID:	32359360
قاعدة البيانات:	MEDLINE

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تدمد:	1742-2094
DOI:	10.1186/s12974-020-01804-6