TY - JOUR
T1 - Radioimmunotherapy combating biofilm-associated infection in vitro
AU - Ye, Zijian
AU - van der Wildt, Berend
AU - Nurmohamed, F. Ruben H.A.
AU - van Duyvenbode, J. Fred F.Hooning
AU - van Strijp, Jos
AU - Vogely, H. Charles
AU - Lam, Marnix G.E.H.
AU - Dadachova, Ekaterina
AU - Weinans, Harrie
AU - van der Wal, Bart C.H.
AU - Poot, Alex J.
N1 - Publisher Copyright:
Copyright © 2024 Ye, van der Wildt, Nurmohamed, van Duyvenbode, van Strijp, Vogely, Lam, Dadachova, Weinans, van der Wal and Poot.
PY - 2024/11/29
Y1 - 2024/11/29
N2 - Background: 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 Staphylococcus aureus (S. aureus) further complicates the scenario. Objective: To investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections. Methods: Our methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on S. aureus and its biofilm. These antibodies were linked with radionuclides actinium-225 (225Ac) and lutetium-177 (177Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of S. aureus and its biofilm to radioimmunotherapy in vitro, assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays. Results: Both [225Ac]4497-IgG1 and [177Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in S. aureus 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 [225Ac]4497-IgG1 and [177Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [225Ac]4497-IgG1 and 14.8 Mbq [177Lu]4497-IgG1 led to reductions of two and four logs, respectively. Conclusion: Our findings underscore the effectiveness of [225Ac]4497-IgG1 and [177Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. aureus and biofilms in vitro. This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. aureus and its biofilm.
AB - Background: 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 Staphylococcus aureus (S. aureus) further complicates the scenario. Objective: To investigate the potential of radioimmunotherapy as an innovative intervention to tackle biofilm-associated infections. Methods: Our methodology involved employing specific monoclonal antibodies 4497-IgG1, designed for targeting wall teichoic acids found on S. aureus and its biofilm. These antibodies were linked with radionuclides actinium-225 (225Ac) and lutetium-177 (177Lu) using DOTA as a chelator. Following this, we evaluated the susceptibility of S. aureus and its biofilm to radioimmunotherapy in vitro, assessing bacterial viability and metabolic activity via colony-forming unit enumeration and xylenol tetrazolium assays. Results: Both [225Ac]4497-IgG1 and [177Lu]4497-IgG1 exhibited a noteworthy dose-dependent reduction in S. aureus 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 [225Ac]4497-IgG1 and [177Lu]4497-IgG1 resulted in a four-log reduction in planktonic bacterial counts. Within biofilms, 14.8 kBq of [225Ac]4497-IgG1 and 14.8 Mbq [177Lu]4497-IgG1 led to reductions of two and four logs, respectively. Conclusion: Our findings underscore the effectiveness of [225Ac]4497-IgG1 and [177Lu]4497-IgG1 antibodies in exerting dose-dependent bactericidal effects against planktonic S. aureus and biofilms in vitro. This suggests that radioimmunotherapy might serve as a promising targeted treatment approach for combating S. aureus and its biofilm.
KW - actinium-225
KW - antibodies
KW - biofilm
KW - infection
KW - lutetium-177
KW - radioimmunotherapy
KW - Staphylococcus aureus
KW - wall teichoic acids
UR - http://www.scopus.com/inward/record.url?scp=85211628604&partnerID=8YFLogxK
U2 - 10.3389/fmed.2024.1478636
DO - 10.3389/fmed.2024.1478636
M3 - Article
AN - SCOPUS:85211628604
SN - 2296-858X
VL - 11
JO - Frontiers in medicine
JF - Frontiers in medicine
M1 - 1478636
ER -