Preparation of <sup>99m</sup>Tc Labeled Anti-Aspergillus Monoclonal Antibody and Biodistribution in Normal Mice_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

DangYajie ¹ , LiXiao ² , ZhengMingrui ³ , LiuHaixia ⁴ , ZhouXia ⁵ ,  JinXianqiao ⁵

1. Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China;
2. ;
3. ;
4. ;
5. ;

Corresponding author：

JinXianqiao, Email: jinxianqiao@126.com

Keywords：

Isotope-labeling; Aspergillus fumigatus; Monoclonal antibody; Biodistribution

DOI：

10.7507/1671-6205.2016083

Video：

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Objective To explore the method of radiolabeling anti-Aspergillus monoclonal antibody (WF-AF-1)with ^99mTc,and evaluate the in vitro and in vivo characteristics of ^99mTc labeled WF-AF-1 (^99mTc-WF-AF-1). Methods ^99mTc-WF-AF-1 was prepared with indirect-labeling method.The labeled product was identified using thin layer chromatography.Suspensions of Aspergillus fumigatus,Staphylococcus aureus and Candida albicans were incubated with ^99mTc-WF-AF-1 to evaluate the specificity of the labeled antibody.Mice were injected with 3.7MBq of labeled product.The biodistribution was measured at 40min,2h,4h and 7h after injection. Results The labeling efficiency of ^99mTc-WF-AF-1 was over 95%,and the labeled product was stable in serum and phosphate buffer solution.In vitro binding of ^99mTc-WF-AF-1 revealed that the labeled Mab-WF-AF-1 preferentially binds to Aspergillus fumigatus. Biodistrbution data showed that the labeled antibody was deposited mainly in liver,kidneys and spleen.The radioactivity uptake in blood at 40min and 7h was (2.51±0.23)%ID/g and (0.53±0.13)%ID/g,respectively. Conclusions The labeling efficiency and stability of ^99mTc-WF-AF-1 are high.The labeled antibody is excreted mainly through the liver and kidneys with fast clearance in blood in normal mice.

Citation： DangYajie, LiXiao, ZhengMingrui, LiuHaixia, ZhouXia, JinXianqiao. Preparation of ^99mTc Labeled Anti-Aspergillus Monoclonal Antibody and Biodistribution in Normal Mice. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(4): 351-355. doi: 10.7507/1671-6205.2016083 Copy

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19.	郑明睿, 刘海霞,党亚洁,等.烟曲霉暴露对哮喘大鼠气道炎症、气道反应性及血清总IgE水平的影响.中国呼吸与危重监护杂志,2015,14:27-31.
20.	Currie BP,Casadevall A.Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City.Clin Infect Dis,1994,19:1029-1033.
21.	Halpern SE,Hagan PL,Chen A,et al.Distribution of radiolabeled human and mouse monoclonal IgM antibodies in murine models.J Nucl Med,1988,29:1688-1696.
22.	Ashwell G,Harford J.Carbohydrate-specific receptors of the liver.Annu Rev Biochem,1982,51:531-554.
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24.	Badiee P,Hashemizadeh Z.Opportunistic invasive fungal infections:diagnosis & clinical management.Indian J Med Res,2014,139:195-204.

1. Sugui JA,Kwon-Chung KJ,Juvvadi PR,et al.Aspergillus fumigatus and related species.Cold Spring Harb Perspect Med,2014,5:a019786.
2. Knutsen AP,Bush RK,Demain JG,et al.Fungi and allergic lower respiratory tract diseases.J Allergy Clin Immunol,2012,129:280-291; quiz 292-293.
3. Kwon-Chung KJ,Sugui JA.Aspergillus fumigatus--what makes the species a ubiquitous human fungal pathogen? PLoS Pathog,2013,9:e1003743.
4. Karthaus M,Buchheidt D.Invasive aspergillosis:new insights into disease,diagnostic and treatment.Curr Pharm Des,2013,19:3569-3594.
5. Jensen HE,Halbaek B,Lind P,et al.Development of murine monoclonal antibodies for the immunohistochemical diagnosis of systemic bovine aspergillosis.J Vet Diagn Invest,1996,8:68-75.
6. Choi JK,Mauger J,McGowan KL.Immunohistochemical detection of Aspergillus species in pediatric tissue samples.Am J Clin Pathol,2004,121:18-25.
7. 周晓谦, 杨秀敏,王毓新,等.应用Envision免疫组化二步法诊断曲霉菌性鼻窦炎.中国麻风皮肤病杂志,2006,22:720-722.
8. 李原, 杨大章,潘琳,等.免疫组织化学法在鼻窦真菌球诊断中的价值.中华耳鼻咽喉科杂志,2004,39:37-39.
9. Akhtar MS,Imran MB,Nadeem MA,et al.Antimicrobial peptides as infection imaging agents:better than radiolabeled antibiotics.Int J Pept, 2012,2012:965238.
10. 王妍, 龙飞,祁卉卉,等.烟曲霉菌孢子对哮喘大鼠气道炎症和气道反应性的影响.中国呼吸与危重监护杂志,2007,6:185-190.
11. 高福生, 金先桥,乔建瓯,等.慢性烟曲霉暴露对哮喘大鼠气道上皮细胞损伤及表皮生长因子受体表达的影响.中国呼吸与危重监护杂志,2010,9:115-121.
12. Cheng D,Zou W,Li X,et al.Preparation and evaluation of Tc-labeled anti-CD11b antibody targeting inflammatory microenvironment for colon cancer imaging.Chem Biol Drug Des,2015,85:696-701.
13. Wang Y,Liu X,Hnatowich DJ.An improved synthesis of NHS-MAG3 for conjugation and radiolabeling of biomolecules with Tc at room temperature.Nat Protoc,2007,2:972-978.
14. Perfect JR,Cox GM,Lee JY,et al.The impact of culture isolation of Aspergillus species:a hospital-based survey of aspergillosis.Clin Infect Dis,2001,33:1824-1833.
15. Torres HA,Rivero GA,Lewis RE,et al.Aspergillosis caused by non-fumigatus Aspergillus species:risk factors and in vitro susceptibility compared with Aspergillus fumigatus.Diagn Microbiol Infect Dis,2003,46:25-28.
16. Gao FS,Qiao JO,Zhang Y,et al.Chronic intranasal administration of Aspergillus fumigatus spores leads to aggravation of airway inflammation and remodelling in asthmatic rats.Respirology,2009,14:360-370.
17. 刘海霞, 金先桥,郑明睿,等.慢性烟曲霉暴露对哮喘大鼠气道嗜酸粒细胞性炎症及气道高反应性的影响.中国呼吸与危重监护杂志,2014,13:28-33.
18. Liu H,Zheng M,Qiao J,et al.Role of prostaglandin D2/CRTH2 pathway on asthma exacerbation induced by Aspergillus fumigatus.Immunology,2014,142:78-88.
19. 郑明睿, 刘海霞,党亚洁,等.烟曲霉暴露对哮喘大鼠气道炎症、气道反应性及血清总IgE水平的影响.中国呼吸与危重监护杂志,2015,14:27-31.
20. Currie BP,Casadevall A.Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City.Clin Infect Dis,1994,19:1029-1033.
21. Halpern SE,Hagan PL,Chen A,et al.Distribution of radiolabeled human and mouse monoclonal IgM antibodies in murine models.J Nucl Med,1988,29:1688-1696.
22. Ashwell G,Harford J.Carbohydrate-specific receptors of the liver.Annu Rev Biochem,1982,51:531-554.
23. Vieira P,Rajewsky K.The half-lives of serum immunoglobulins in adult mice.Eur J Immunol,1988,18:313-316.
24. Badiee P,Hashemizadeh Z.Opportunistic invasive fungal infections:diagnosis & clinical management.Indian J Med Res,2014,139:195-204.

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Preparation of ^99mTc Labeled Anti-Aspergillus Monoclonal Antibody and Biodistribution in Normal Mice

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Preparation of ^99mTc Labeled Anti-Aspergillus Monoclonal Antibody and Biodistribution in Normal Mice