Ye Zijian, van der Wildt Berend, Nurmohamed F Ruben H A, van Duyvenbode J Fred F Hooning, van Strijp Jos, Vogely H Charles, Lam Marnix G E H, Dadachova Ekaterina, Weinans Harrie, van der Wal Bart C H, Poot Alex J
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, Netherlands.
Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
Front Med (Lausanne). 2024 Nov 29;11:1478636. doi: 10.3389/fmed.2024.1478636. eCollection 2024.
Addressing prosthetic joint infections poses a significant challenge within orthopedic surgery, marked by elevated morbidity and mortality rates. The presence of biofilms and infections attributed to () further complicates the scenario.
To investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections.
Our methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on and its biofilm. These antibodies were linked with radionuclides actinium-225 (Ac) and lutetium-177 (Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of and its biofilm to radioimmunotherapy , assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays.
Both [Ac]4497-IgG1 and [Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in in planktonic cultures and biofilms over a 96-h exposure period, compared to non-specific antibody control groups. Specifically, doses of 7.4 kBq and 7.4 MBq of [Ac]4497-IgG1 and [Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [Ac]4497-IgG1 and 14.8 Mbq [Lu]4497-IgG1 led to reductions of two and four logs, respectively.
Our findings underscore the effectiveness of [Ac]4497-IgG1 and [Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. and biofilms . This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. and its biofilm.
解决人工关节感染是骨科手术中的一项重大挑战,其特点是发病率和死亡率升高。生物膜的存在以及由()引起的感染使情况更加复杂。
研究放射免疫疗法作为一种创新干预措施来应对生物膜相关感染的潜力。
我们的方法包括使用特定的单克隆抗体4497-IgG1,其设计用于靶向在()及其生物膜上发现的壁磷壁酸。这些抗体使用DOTA作为螯合剂与放射性核素锕-225(Ac)和镥-177(Lu)连接。在此之后,我们评估了()及其生物膜对放射免疫疗法的敏感性,通过菌落形成单位计数和二甲苯四氮唑测定法评估细菌活力和代谢活性。
与非特异性抗体对照组相比,在96小时的暴露期内,[Ac]4497-IgG1和[Lu]4497-IgG1在浮游培养物和生物膜中均表现出显著的剂量依赖性细菌数量减少。具体而言,7.4 kBq和7.4 MBq的[Ac]4497-IgG1和[Lu]4497-IgG1剂量导致浮游细菌数量减少四个对数。在生物膜中,14.8 kBq的[Ac]4497-IgG1和14.8 Mbq的[Lu]4497-IgG1分别导致细菌数量减少两个和四个对数。
我们的研究结果强调了[Ac]4497-IgG1和[Lu]4497-IgG1抗体对浮游的()和生物膜具有剂量依赖性杀菌作用。这表明放射免疫疗法可能是对抗()及其生物膜的一种有前途的靶向治疗方法。