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体内用放射性标记抗体评估 - 感染植入物的靶向性。

Evaluating the Targeting of a -Infected Implant with a Radiolabeled Antibody In Vivo.

机构信息

Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

Department of Medical Microbiology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands.

出版信息

Int J Mol Sci. 2023 Feb 22;24(5):4374. doi: 10.3390/ijms24054374.

Abstract

Implant infections caused by are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting and provide evidence of the specificity and biodistribution of --targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in was labeled with indium-111 using CHX-A"-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm at 24 h to 9.22 %ID/cm at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm at 120 h. The effective half-life of In-4497 mAbs was determined to be 59 h. In conclusion, In-4497 mAbs were found to specifically detect and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm.

摘要

植入物感染由于生物膜的形成而难以治疗,这使得手术和抗生素治疗变得复杂。我们引入了一种使用针对 的单克隆抗体 (mAb) 的替代方法,并提供了在小鼠植入物感染模型中针对 - 靶向抗体的特异性和生物分布的证据。使用 CHX-A"-DTPA 作为螯合剂,用铟-111 标记针对 的壁磷壁酸的单克隆抗体 4497-IgG1。在 Balb/cAnNCrl 小鼠的皮下植入物上预先定植了 生物膜后,在植入物感染前 24、72 和 120 小时进行单光子发射计算机断层扫描/计算机断层扫描扫描。使用 SPECT/CT 成像可视化和定量分析该标记抗体在各种器官中的分布,并将其与目标组织中的摄取进行比较。在感染的植入物中,In-4497 mAb 的摄取逐渐从 24 小时的 8.34 %ID/cm 增加到 120 小时的 9.22 %ID/cm。随着时间的推移,心脏/血池中的摄取从 11.60 减少到 7.58 %ID/cm,而其他器官中的摄取从 7.26 减少到 120 小时时不到 4.66 %ID/cm。In-4497 mAb 的有效半衰期确定为 59 小时。总之,发现 In-4497 mAb 特异性检测 及其生物膜,在定植植入物部位具有优异和持久的积累。因此,它有可能作为诊断和杀菌治疗生物膜的药物输送系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d9f/10002501/5891c9ecb602/ijms-24-04374-g001.jpg

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