<sup>18</sup>F‑fluorodeoxyglucose positron emission tomography for the detection of inflammatory lesions of the arterial vessel walls in Wistar rats

Shen,Shiwei; Li,Hongwei; Ge,Song; Huang,Hongbo; Zhang,Hui; Li,Feng; Feng,Yinbo; Wang,Ling; Weng,Xiaofeng; Lu,Yun; Shen,Zhenhai

doi:10.3892/etm.2021.9801

¹⁸F‑fluorodeoxyglucose positron emission tomography for the detection of inflammatory lesions of the arterial vessel walls in Wistar rats

Authors:
- Shiwei Shen
- Hongwei Li
- Song Ge
- Hongbo Huang
- Hui Zhang
- Feng Li
- Yinbo Feng
- Ling Wang
- Xiaofeng Weng
- Yun Lu
- Zhenhai Shen
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Affiliations: Department of Endocrinology, Wuxi No. 2 People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China, Department of Rehabilitation, Jiangsu Provincial Research Center for Health Assessment and Intervention, Jiangsu Provincial Taihu Sanatorium, Wuxi, Jiangsu 214086, P.R. China, Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Micro PET Center, Jiangsu Institution of Nuclear Medicine, Wuxi, Jiangsu 214063, P.R. China, Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Internal Medicine, Jiangsu Provincial Research Center for Health Assessment and Intervention, Jiangsu Provincial Taihu Sanatorium, Wuxi, Jiangsu 214086, P.R. China, Department of Radiology, Jiangsu Provincial Research Center for Health Assessment and Intervention, Jiangsu Provincial Taihu Sanatorium, Wuxi, Jiangsu 214086, P.R. China, Clinical Laboratory, Jiangsu Provincial Research Center for Health Assessment and Intervention, Jiangsu Provincial Taihu Sanatorium, Wuxi, Jiangsu 214086, P.R. China
Published online on: February 19, 2021 https://doi.org/10.3892/etm.2021.9801
Article Number: 370
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to evaluate the use of ¹⁸F‑fluorodeoxyglucose (¹⁸F‑FDG) positron emission tomography (PET) for detection of high‑fat and high‑salt diet‑induced inflammatory lesions of the arterial vessel walls in Wistar rats. A total of 20 healthy, 8‑week‑old, male Wistar rats were randomly assigned to the high‑fat diet group and the normal diet group. After 16 and 24 weeks of feeding, Wistar rats in the normal diet group and the high‑fat diet group (five rats in each group) were injected with ¹⁸F‑FDG through the tail vein at a dose of 1 mCi/kg after fasting for 12 h. After 1 h, the rats were anesthetized with 2% isoflurane, followed by micro‑PET imaging with a 10‑min image capture duration and immunohistochemical staining. The standardized uptake values (SUVs) of ¹⁸F‑FDG were significantly higher in the iliac artery in the high‑fat diet group compared with those in the normal diet group at 16 weeks (1.53±0.08 vs. 1.04±0.03; P<0.05) and at 24 weeks (1.96±0.17 vs. 1.12±0.07; P<0.05). The SUVs of ¹⁸F‑FDG were also significantly greater in the abdominal aorta in the high‑fat diet group compared with those in the normal diet group at 16 weeks (1.35±0.08 vs. 1.02±0.02; P<0.05) and at 24 weeks (1.54±0.09 vs. 1.04±0.02; P<0.05). In addition, the SUVs of 18F‑FDG in the iliac artery and abdominal aorta were significantly higher at 24 weeks compared with those at 16 weeks in the high‑fat diet group (P<0.05). As determined by immunohistochemistry, the percentage of CD68‑positive cells in the total number of cells per unit area in each group was 3.20±1.80% in the 24‑week normal diet group, 4.70±2.02% in the 16‑week high‑fat diet group and 6.94±2.02% in the 24‑week high‑fat diet group; the percentage of CD68‑positive cells in the high‑fat diet group at 24 weeks was significantly higher than that in the high‑fat diet group at 16 weeks and in the normal diet group at 24 weeks (P<0.05). In conclusion, ¹⁸F‑FDG PET is a noninvasive imaging tool that can continuously monitor inflammatory lesions of the arterial vessel walls in Wistar rats. Further improvement of the Wistar rat atherosclerosis model may provide data to support the early assessment of and intervention in atherosclerosis.

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1	National Center for Cardiovascular Disease: China. Report on Cardiovascular disease in China (2016). Encyclopedia of China Publishing House, Beijing, 2017.
2	Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, Ahmed M, Aksut B, Alam T, Alam K, et al: Global, regional and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 70:1–25. 2017.PubMed/NCBI View Article : Google Scholar
3	McKenney-Drake ML, Moghbel MC, Paydary K, Alloosh M, Houshmand S, Moe S, Salavati A, Sturek JM, Territo PR, Weaver C, et al: ¹⁸F-NaF and ¹⁸F-FDG as molecular probes in the evaluation of atherosclerosis. Eur J Nucl Med Mol Imaging. 45:2190–2200. 2018.PubMed/NCBI View Article : Google Scholar
4	Ross R: Atherosclerosis - an inflammatory disease. N Engl J Med. 340:115–126. 1999.PubMed/NCBI View Article : Google Scholar
5	Fan LM: Rethinking the pathogenesis of atherosclerosis. Chin J Arterioscler. 13:249–253. 2005.
6	Hosono M, de Boer OJ, van der Wal AC, van der Loos CM, Teeling P, Piek JJ, Ueda M and Becker AE: Increased expression of T cell activation markers (CD25, CD26, CD40L and CD69) in atherectomy specimens of patients with unstable angina and acute myocardial infarction. Atherosclerosis. 168:73–80. 2003.PubMed/NCBI View Article : Google Scholar
7	Chen W, Bural GG, Torigian DA, Rader DJ and Alavi A: Emerging role of FDG-PET/CT in assessing atherosclerosis in large arteries. Eur J Nucl Med Mol Imaging. 36:144–151. 2009.PubMed/NCBI View Article : Google Scholar
8	Wang ZJ, Deng G, Huang HB, Li AM, Ju SH, Zhao R, Jin H and Wei XY: Noninvasive observation of atherosclerosis in mice with 7.0T MR and Micro-PET. Chin J Med Imaging Technol. 26:209–212. 2010.
9	Ogawa M, Ishino S, Mukai T, Asano D, Teramoto N, Watabe H, Kudomi N, Shiomi M, Magata Y, Iida H, et al: (18)F-FDG accumulation in atherosclerotic plaques: Immunohistochemical and PET imaging study. J Nucl Med. 45:1245–1250. 2004.PubMed/NCBI
10	Tawakol A, Migrino RQ, Hoffmann U, Abbara S, Houser S, Gewirtz H, Muller JE, Brady TJ and Fischman AJ: Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol. 12:294–301. 2005.PubMed/NCBI View Article : Google Scholar
11	Feng TT and Zhao QM: Advances of PET/CT in noninvasive assessing of atherosclerosis plaque. Chin J Med Imaging Technol. 26:971–973. 2010.
12	Lau AZ, Miller JJ, Robson MD and Tyler DJ: Cardiac perfusion imaging using hyperpolarized (13)C urea using flow sensitizing gradients. Magn Reson Med. 75:1474–1483. 2016.PubMed/NCBI View Article : Google Scholar
13	Di Cesare Mannelli L, Micheli L, Carta F, Cozzi A, Ghelardini C and Supuran CT: Carbonic anhydrase inhibition for the management of cerebral ischemia: In vivo evaluation of sulfonamide and coumarin inhibitors. J Enzyme Inhib Med Chem. 31:894–899. 2016.PubMed/NCBI View Article : Google Scholar
14	Pan L, Yang F, Lu C, Jia C, Wang Q and Zeng K: Effects of sevoflurane on rats with ischemic brain injury and the role of the TREK-1 channel. Exp Ther Med. 14:2937–2942. 2017.PubMed/NCBI View Article : Google Scholar
15	Li S, et al: Comparative study on anesthetic role of chloral hydrate on rat. Drug Res. 23:22–23. 2014.
16	Wang JF: Guidelines for the Management and Use of Laboratory Animals. Shanghai Science and Technology Press, 2012.
17	Tabas I and Bornfeldt KE: Macrophage phenotype and function in different stages of atherosclerosis. Circ Res. 118:653–667. 2016.PubMed/NCBI View Article : Google Scholar
18	Zhang Y, Zhang C and Zhang M: A new era of anti-inflammatory therapy for atherosclerosis. Zhonghua Xin Xue Guan Bing Za Zhi. 46:332–337. 2018.PubMed/NCBI View Article : Google Scholar : (In Chinese).
19	Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N and Ido T: Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: High accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med. 33:1972–1980. 1992.PubMed/NCBI
20	Tatsumi M, Cohade C, Nakamoto Y and Wahl RL: Fluorodeoxyglucose uptake in the aortic wall at PET/CT: Possible finding for active atherosclerosis. Radiology. 229:831–837. 2003.PubMed/NCBI View Article : Google Scholar
21	Cullen P, Baetta R, Bellosta S, Bernini F, Chinetti G, Cignarella A, von Eckardstein A, Exley A, Goddard M, Hofker M, et al: MAFAPS Consortium: Rupture of the atherosclerotic plaque: Does a good animal model exist? Arterioscler Thromb Vasc Biol. 23:535–542. 2003.PubMed/NCBI View Article : Google Scholar
22	Ogawa M, Magata Y, Kato T, Hatano K, Ishino S, Mukai T, Shiomi M, Ito K and Saji H: Application of ¹⁸F-FDG PET for monitoring the therapeutic effect of antiinflammatory drugs on stabilization of vulnerable atherosclerotic plaques. J Nucl Med. 47:1845–1850. 2006.PubMed/NCBI
23	Matter CM, Wyss MT, Meier P, Späth N, von Lukowicz T, Lohmann C, Weber B, Ramirez de Molina A, Lacal JC, Ametamey SM, et al: ¹⁸F-choline images murine atherosclerotic plaques ex vivo. Arterioscler Thromb Vasc Biol. 26:584–589. 2006.PubMed/NCBI View Article : Google Scholar
24	Zhao QM, Feng TT, Zhao X, Xu ZM, Liu Y, Li DP, Li LQ, Su G and Zhang XX: Imaging of atherosclerotic aorta of rabbit model by detection of plaque inflammation with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography. Chin Med J (Engl). 124:911–917. 2011.PubMed/NCBI
25	Knesaurek K, Machac J, Vallabhajosula S and Buchsbaum MS: A new iterative reconstruction technique for attenuation correction in high-resolution positron emission tomography. Eur J Nucl Med. 23:656–661. 1996.PubMed/NCBI View Article : Google Scholar
26	Lederman RJ, Raylman RR, Fisher SJ, Kison PV, San H, Nabel EG and Wahl RL: Detection of atherosclerosis using a novel positron-sensitive probe and 18-fluorodeoxyglucose (FDG). Nucl Med Commun. 22:747–753. 2001.PubMed/NCBI View Article : Google Scholar
27	Wang XN, et al: Application of ¹⁸F-FDG nuclide imaging of atherosclerotic plaques in apolipoprotein E-deficient mice. J Chin PLA Postgrad Med Sch. 6:645–647. 2011.
28	Wang HR and Yu CJ: New progress in mechanism and treatment of atherosclerosis. J Cap Med Univ. 31:828–833. 2010.
29	Zhang YL, et al: Method of establishment of model of experimental atherosclerosis in rats. J Wenzhou Med Coll. 37:331–333. 2007.
30	Xue YQ and Huang SA: A fast method of establishment of atherosclerotic rat model. Med Innov Chin. 11:1–4. 2014.
31	Zhou H, Wu XY, Yuan YB and Qi XH: Comparison of methods for establishing a rat model of atherosderosis using three-doses of Vitamin D3 and atherogenic diet. Chin J Arterioscler. 20:995–998. 2012.
32	Guo YS, et al: Comparison on the three duplication methods of atherosclerosis model in rat. Chin J Arterioscler. 11:465–469. 2003.
33	Hu H, Xu Y, Liu C, Zhao H, Zhang H and Wang L: Changes in behavior and in brain glucose metabolism in rats after nine weeks on a high fat diet: A randomized controlled trial. Shanghai Arch Psychiatry. 26:129–137. 2014.PubMed/NCBI View Article : Google Scholar
34	Dobrian AD, Davies MJ, Prewitt RL and Lauterio TJ: Development of hypertension in a rat model of diet-induced obesity. Hypertension. 35:1009–1015. 2000.PubMed/NCBI View Article : Google Scholar
35	Hamman RF: Genetic and environmental determinants of non-insulin-dependent diabetes mellitus (NIDDM). Diabetes Metab Rev. 8:287–338. 1992.PubMed/NCBI View Article : Google Scholar
36	Tankó LB, Bagger YZ, Alexandersen P, Larsen PJ and Christiansen C: Peripheral adiposity exhibits an independent dominant antiatherogenic effect in elderly women. Circulation. 107:1626–1631. 2003.PubMed/NCBI View Article : Google Scholar
37	Chen J: Dietary capsaicin prevents insulin resistance in high fat diet-induced mice. Di 3 Jun Yi Da Xue Xue Bao. 35:585–588. 2013.(In Chinese).
38	Alexander RW: President's address. Common mechanisms of multiple diseases: Why vegetables and exercise are good for you. Trans Am Clin Climatol Assoc. 121:1–20. 2010.PubMed/NCBI
39	Zhang Z, Machac J, Helft G, Worthley SG, Tang C, Zaman AG, Rodriguez OJ, Buchsbaum MS, Fuster V and Badimon JJ: Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: A histopathological correlation. BMC Nucl Med. 6(3)2006.PubMed/NCBI View Article : Google Scholar
40	Nahrendorf M, Zhang H, Hembrador S, Panizzi P, Sosnovik DE, Aikawa E, Libby P, Swirski FK and Weissleder R: Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation. 117:379–387. 2008.PubMed/NCBI View Article : Google Scholar
41	Aziz K, Berger K, Claycombe K, Huang R, Patel R and Abela GS: Noninvasive detection and localization of vulnerable plaque and arterial thrombosis with computed tomography angiography/positron emission tomography. Circulation. 2061–2070. 2008.PubMed/NCBI View Article : Google Scholar
42	Bucerius J, Dijkgraaf I, Mottaghy FM and Schurgers LJ: Target identification for the diagnosis and intervention of vulnerable atherosclerotic plaques beyond ¹⁸F-fluorodeoxyglucose positron emission tomography imaging: Promising tracers on the horizon. Eur J Nucl Med Mol Imaging. 46:251–265. 2019.PubMed/NCBI View Article : Google Scholar
43	Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, Yates D, LaMuraglia GM, Furie K, Houser S, et al: In vivo ¹⁸F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 48:1818–1824. 2006.PubMed/NCBI View Article : Google Scholar
44	Pahk K, Joung C, Jung SM, Young Song H, Yong Park J, Woo Byun J, Lee YS, Chul Paeng J, Kim C, Kim S, et al: Visualization of synthetic vascular smooth muscle cells in atherosclerotic carotid rat arteries by F-18 FDG PET. Sci Rep. 7(6989)2017.PubMed/NCBI View Article : Google Scholar
45	Evans NR, Tarkin JM, Chowdhury MM, Warburton EA and Rudd JH: PET imaging of atherosclerotic disease: Advancing plaque assessment from anatomy to pathophysiology. Curr Atheroscler Rep. 18(30)2016.PubMed/NCBI View Article : Google Scholar
46	Yang MF: Advancing the clinical application of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in cardiovascular inflammation. Zhonghua Xin Xue Guan Bing Za Zhi. 48:181–185. 2020.PubMed/NCBI View Article : Google Scholar : (In Chinese).
47	Xie B, Chen BX, Wu JY, Liu X and Yang MF: Factors relevant to atrial ¹⁸F-fluorodeoxyglucose uptake in atrial Fibrillation. J Nucl Cardiol. 27:1501–1512. 2018.
48	Sinigaglia M, Mahida B, Piekarski E, Chequer R, Mikail N, Benali K, Hyafil F, Le Guludec D and Rouzet F: FDG atrial uptake is associated with an increased prevalence of stroke in patients with atrial fibrillation. Eur J Nucl Med Mol Imaging. 46:1268–1275. 2019.PubMed/NCBI View Article : Google Scholar