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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Research Article

Bis-iodine-labeled Curcumin as a Potential CT Imaging Agent for β-amyloid Plaques in the Brain

Author(s): Yaqian Dai, Liduo Peng, Xiaoyan Tian, Xingwang Wu, Yuanhong Xu*, Taoshan Jiang* and Jinping Qiao*

Volume 22, Issue 7, 2023

Published on: 31 August, 2022

Page: [1120 - 1132] Pages: 13

DOI: 10.2174/1871527321666220707091435

Price: $65

Abstract

Background: Alzheimer's disease (AD) is one of the most common causes of dementia, affecting many old people.

Objectives: By designing and synthesizing intracerebral imaging probes, we tried to provide a new solution for the early diagnosis of AD.

Methods: We designed and synthesized bis-iodine-labeled curcumin, and verified its performance through in vivo and in vitro experiments.

Results: In this study, bis-iodine-labeled curcumin (7, BICUR) was synthesized. In the in vitro mass spectrum binding assay, Kd values of BICUR with Aβ1-40 and Aβ1-42 aggregates were 46.29 nM and 64.29 nM, respectively. Aβ plaques in AD brain adjacent sections were positively stained by BICUR, which was similar to some other curcumin derivatives. The Log P value of BICUR was 1.45. In the biodistribution experiment, BICUR showed the highest initial brain uptake (5.87% compared to the blood concentration) two minutes after the tail vein injection and rapid clearance from the mouse brain. In the acute toxicity experiment, BICUR showed low toxicity, and the LD50 was >100 mg/kg. Moreover, BICUR showed a high stability in vitro (86.68% unchanged BICUR after incubation for 120min in mouse brain homogenate). Besides, BICUR produced an enhanced CT imaging effect that could be sensitively detected in vitro, but it also showed an obvious differentiation from surrounding tissues after intracerebral injection.

Conclusion: All results suggested that BICUR could probably act as a targeted CT imaging agent for Aβ plaques in the brain.

Keywords: Alzheimer's disease, β-amyloid, curcumin, molecular imaging, Probe, BICUR.

« Previous Next »
[1]
Christina P. ADI - World Alzheimer Report. 2018; 2018. Available from: https://www.alzint.org/resource/world-alzheimer-report-2018/
[2]
Association Alzheimer’s. 2018 Alzheimer’s disease facts and figures. Alzheimers Dement 2018; 3(14): 367-429.
[3]
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 2002; 297(5580): 353-6.
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[4]
Tharp WG, Sarkar IN. Origins of amyloid-β. BMC Genomics 2013; 14: 290.
[http://dx.doi.org/10.1186/1471-2164-14-290] [PMID: 23627794]
[5]
Cummings JL. Alzheimer’s disease. N Engl J Med 2004; 351(1): 56-67.
[http://dx.doi.org/10.1056/NEJMra040223] [PMID: 15229308]
[6]
Arimon M, Díez-Pérez I, Kogan MJ, et al. Fine structure study of Abeta1-42 fibrillogenesis with atomic force microscopy. FASEB J 2005; 19(10): 1344-6.
[http://dx.doi.org/10.1096/fj.04-3137fje] [PMID: 15919759]
[7]
Rowe CC, Villemagne VL. Brain amyloid imaging. J Nucl Med Technol 2013; 41(1): 11-8.
[PMID: 23396994]
[8]
Maya Y, Okumura Y, Kobayashi R, et al. Preclinical properties and human in vivo assessment of 123I-ABC577 as a novel SPECT agent for imaging amyloid-β. Brain 2016; 139(Pt 1): 193-203.
[http://dx.doi.org/10.1093/brain/awv305] [PMID: 26490333]
[9]
Connor DM, Benveniste H, Dilmanian FA, Kritzer MF, Miller LM, Zhong Z. Computed tomography of amyloid plaques in a mouse model of Alzheimer’s disease using diffraction enhanced imaging. Neuroimage 2009; 46(4): 908-14.
[http://dx.doi.org/10.1016/j.neuroimage.2009.03.019] [PMID: 19303447]
[10]
Lusic H, Grinstaff MW. X-ray-computed tomography contrast agents. Chem Rev 2013; 113(3): 1641-66.
[http://dx.doi.org/10.1021/cr200358s] [PMID: 23210836]
[11]
Rokka J, Snellman A, Zona C, et al. Synthesis and evaluation of a (18)F-curcumin derivate for β-amyloid plaque imaging. Bioorg Med Chem 2014; 22(9): 2753-62.
[http://dx.doi.org/10.1016/j.bmc.2014.03.010] [PMID: 24702859]
[12]
Ryu EK, Choe YS, Lee KH, Choi Y, Kim BT. Curcumin and dehydrozingerone derivatives: Synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging. J Med Chem 2006; 49(20): 6111-9.
[http://dx.doi.org/10.1021/jm0607193] [PMID: 17004725]
[13]
Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ. Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 2007; 102(4): 1095-104.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04613.x] [PMID: 17472706]
[14]
Prasad S, Gupta SC, Tyagi AK, Aggarwal BB. Curcumin, a component of golden spice: From bedside to bench and back. Biotechnol Adv 2014; 32(6): 1053-64.
[http://dx.doi.org/10.1016/j.biotechadv.2014.04.004] [PMID: 24793420]
[15]
Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res 2003; 23(1A): 363-98.
[PMID: 12680238]
[16]
Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: From kitchen to clinic. Biochem Pharmacol 2008; 75(4): 787-809.
[http://dx.doi.org/10.1016/j.bcp.2007.08.016] [PMID: 17900536]
[17]
Salehi B, Stojanović-Radić Z, Matejić J, et al. The therapeutic potential of curcumin: A review of clinical trials. Eur J Med Chem 2019; 163: 527-45.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.016] [PMID: 30553144]
[18]
Pan MH, Huang TM, Lin JK. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 1999; 27(4): 486-94.
[PMID: 10101144]
[19]
Tønnesen HH, Karlsen J. Studies on curcumin and curcuminoids. VI. Kinetics of curcumin degradation in aqueous solution. Z Lebensm Unters Forsch 1985; 180(5): 402-4.
[PMID: 4013525]
[20]
Wang YJ, Pan MH, Cheng AL, et al. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 1997; 15(12): 1867-76.
[http://dx.doi.org/10.1016/S0731-7085(96)02024-9] [PMID: 9278892]
[21]
Goozee KG, Shah TM, Sohrabi HR, et al. Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer’s disease. Br J Nutr 2016; 115(3): 449-65.
[http://dx.doi.org/10.1017/S0007114515004687] [PMID: 26652155]
[22]
Yang F, Lim GP, Begum AN, et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 2005; 280(7): 5892-901.
[http://dx.doi.org/10.1074/jbc.M404751200] [PMID: 15590663]
[23]
Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, et al. Identification of amyloid plaques in retinas from Alzheimer’s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage 2011; 54 (Suppl. 1): S204-17.
[http://dx.doi.org/10.1016/j.neuroimage.2010.06.020] [PMID: 20550967]
[24]
Kung MP, Hou C, Zhuang ZP, Skovronsky D, Kung HF. Binding of two potential imaging agents targeting amyloid plaques in postmortem brain tissues of patients with Alzheimer’s disease. Brain Res 2004; 1025(1-2): 98-105.
[http://dx.doi.org/10.1016/j.brainres.2004.08.004] [PMID: 15464749]
[25]
Kung MP, Hou C, Zhuang ZP, et al. IMPY: An improved thioflavin-T derivative for in vivo labeling of beta-amyloid plaques. Brain Res 2002; 956(2): 202-10.
[http://dx.doi.org/10.1016/S0006-8993(02)03436-4] [PMID: 12445687]
[26]
Uzuegbunam BC, Librizzi D, Hooshyar Yousefi B. PET radiopharmaceuticals for Alzheimer’s disease and Parkinson’s disease diagnosis, the current and future landscape. Molecules 2020; 25(4): 977.
[http://dx.doi.org/10.3390/molecules25040977] [PMID: 32098280]
[27]
Budson AE, Solomon PR. New criteria for Alzheimer disease and mild cognitive impairment: Implications for the practicing clinician. Neurologist 2012; 18(6): 356-63.
[http://dx.doi.org/10.1097/NRL.0b013e31826a998d] [PMID: 23114667]
[28]
Qiao JP, Gan CS, Wang CW, et al. Novel indanone derivatives as potential imaging probes for β-amyloid plaques in the brain. ChemBioChem 2012; 13(11): 1652-62.
[http://dx.doi.org/10.1002/cbic.201200223] [PMID: 22777884]
[29]
Gan C, Hu J, Nan DD, Wang S, Li H. Synthesis and biological evaluation of curcumin analogs as β-amyloid imaging agents. Future Med Chem 2017; 9(14): 1587-96.
[http://dx.doi.org/10.4155/fmc-2017-0079] [PMID: 28841047]
[30]
Hirohata M, Hasegawa K, Tsutsumi-Yasuhara S, et al. The anti-amyloidogenic effect is exerted against Alzheimer’s beta-amyloid fibrils in vitro by preferential and reversible binding of flavonoids to the amyloid fibril structure. Biochemistry 2007; 46(7): 1888-99.
[http://dx.doi.org/10.1021/bi061540x] [PMID: 17253770]
[31]
Ge JF, Qiao JP, Qi CC, Wang CW, Zhou JN. The binding of resveratrol to monomer and fibril amyloid beta. Neurochem Int 2012; 61(7): 1192-201.
[http://dx.doi.org/10.1016/j.neuint.2012.08.012] [PMID: 22981725]
[32]
Grimm SH, Höfner G, Wanner KT. Development and validation of an LC-ESI-MS/MS method for the triple reuptake inhibitor indatraline enabling its quantification in MS Binding Assays. Anal Bioanal Chem 2015; 407(2): 471-85.
[http://dx.doi.org/10.1007/s00216-014-8312-8] [PMID: 25450050]
[33]
Grimm SH, Höfner G, Wanner KT. MS binding assays for the three monoamine transporters using the triple reuptake inhibitor (1r,3s)-indatraline as native marker. ChemMedChem 2015; 10(6): 1027-39.
[http://dx.doi.org/10.1002/cmdc.201500084] [PMID: 25899387]
[34]
Duan XH, Qiao JP, Yang Y, Cui MC, Zhou JN, Liu BL. Novel anilinophthalimide derivatives as potential probes for beta-amyloid plaque in the brain. Bioorg Med Chem 2010; 18(3): 1337-43.
[http://dx.doi.org/10.1016/j.bmc.2009.12.023] [PMID: 20036557]
[35]
Cao Y, Xu RX, Liu Z. A high-throughput quantification method of curcuminoids and curcumin metabolites in human plasma via high-performance liquid chromatography/tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 949-950: 70-8.
[http://dx.doi.org/10.1016/j.jchromb.2013.12.039] [PMID: 24480327]
[36]
Kunati SR, Yang S, William BM, Xu Y. An LC-MS/MS method for simultaneous determination of curcumin, curcumin glucuronide and curcumin sulfate in a phase II clinical trial. J Pharmaceut Biomed 2018; 156: 189-98.
[http://dx.doi.org/10.1016/j.jpba.2018.04.034] [PMID: 29727780]
[37]
Shi H, Niu M, Tan L, et al. A smart all-in-one theranostic platform for CT imaging guided tumor microwave thermotherapy based on IL@ZrO2 nanoparticles. Chem Sci (Camb) 2015; 6(8): 5016-26.
[http://dx.doi.org/10.1039/C5SC00781J] [PMID: 30155006]

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