The Development and Validation of Radiopharmaceuticals Targeting Bacterial Infection

Alberto, Signore; Ordonez, Alvaro A.; Arjun, Chanda; Aulakh, Gurpreet Kaur; Beziere, Nicolas; Dadachova, Ekaterina; Ebenhan, Thomas; Granados, Ulises; Korde, Aruna; Jalilian, Amirreza; Lestari, Wening; Mukherjee, Archana; Petrik, Milos; Sakr, Tamer; Cuevas, Clara L. Santos; Welling, Mick M.; Zeevaart, Jan Rijn; Jain, Sanjay K.; Wilson, David M.

doi:10.2967/jnumed.123.265906

Cited by 10 publications

(4 citation statements)

References 81 publications

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“…Radioimmunoimaging and RIT in the field of infectious diseases in general and in fungal infections in particular is still much behind oncology [37–39]. Developing radioimmunoimaging for opportunistic fungal infections is very important because of the need to diagnose them in an expedited manner as the growth of fungal cultures obtained from patients might take weeks, which is often not feasible for critically ill patients.…”

Section: Discussionmentioning

confidence: 99%

Radioimmunotherapy as a pathogen-agnostic treatment method for opportunistic mucormycosis infections

Carvalho,

Malo,

Allen

et al. 2023

Access Microbiology

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Invasive fungal infections (IFIs) such as mucormycosis are causing devastating morbidity and mortality in immunocompromised patients as anti-fungal agents do not work in the setting of a suppressed immune system. The coronavirus disease 2019 (COVID-19) pandemic has created a novel landscape for IFIs in post-pandemic patients, resulting from severe immune suppression caused by COVID-19 infection, comorbidities (diabetes, obesity) and immunosuppressive treatments such as steroids. The antigen–antibody interaction has been employed in radioimmunotherapy (RIT) to deliver lethal doses of ionizing radiation emitted by radionuclides to targeted cells and has demonstrated efficacy in several cancers. One of the advantages of RIT is its independence of the immune status of a host, which is crucial for immunosuppressed post-COVID-19 patients. In the present work we targeted the fungal pan-antigens 1,3-beta-glucan and melanin pigment, which are present in the majority of pathogenic fungi, with RIT, thus making such targeting pathogen-agnostic. We demonstrated in experimental murine mucormycosis in immunocompetent and immunocompromised mice that lutetium-177 (177Lu)-labelled antibodies to these two antigens effectively decreased the fungal burden in major organs, including the brain. These results are encouraging because they show the effectiveness of pathogen-agnostic RIT in significantly decreasing fungal burden in vivo, while they can also potentially be applied to treat the broad range of invasive fungal infections that express the pan-antigens 1,3-beta-glucan or melanin.

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Section: Discussionmentioning

confidence: 99%

Radioimmunotherapy as a pathogen-agnostic treatment method for opportunistic mucormycosis infections

Carvalho,

Malo,

Allen

et al. 2023

Access Microbiology

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“…Recently, a comprehensive review was published including consensus results, expert opinions, and recommendations regarding the current research standards aiming to improve radiotracers for infection imaging. 33,124 4.1. Precursor Design.…”

Section: Design Approach and Challenges For Translationmentioning

confidence: 99%

“…Developing and validating new radiotracers for more specific imaging of infection are commons goal to improve diagnosis and health care in patients. Recently, a comprehensive review was published including consensus results, expert opinions, and recommendations regarding the current research standards aiming to improve radiotracers for infection imaging. , …”

Section: Design Approach and Challenges For Translationmentioning

confidence: 99%

Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives

Koatale,

Welling,

Ndlovu

et al. 2024

ACS Infect. Dis.

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The unique structural architecture of the peptidoglycan allows for the stratification of bacteria as either Gram-negative or Gram-positive, which makes bacterial cells distinguishable from mammalian cells. This classification has received attention as a potential target for diagnostic and therapeutic purposes. Bacteria's ability to metabolically integrate peptidoglycan precursors during cell wall biosynthesis and recycling offers an opportunity to target and image pathogens in their biological state. This Review explores the peptidoglycan biosynthesis for bacteria-specific targeting for infection imaging. Current and potential radiolabeled peptidoglycan precursors for bacterial infection imaging, their development status, and their performance in vitro and/or in vivo are highlighted. We conclude by providing our thoughts on how to shape this area of research for future clinical translation.

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“…Besides using bacterial cell wall components like D-amino acids or the bacteria specific uptake of complex carbohydrates PET radiotracers targeting the bacteria-specific iron transport system are a possible way. 4 An ideal bacteria-specific PET tracer should exclusively be taken up by bacteria and not by host cells. In order to achieve high sensitivity, a molecular signal amplification strategy would be desirable, e.g.…”

mentioning

confidence: 99%

A novel radiolabelled salmochelin derivative for bacteria-specific PET imaging: synthesis, radiolabelling and evaluation

Margeta,

Schelhaas,

Hermann

et al. 2024

Chem. Commun.

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The Development and Validation of Radiopharmaceuticals Targeting Bacterial Infection

Cited by 10 publications

References 81 publications

Radioimmunotherapy as a pathogen-agnostic treatment method for opportunistic mucormycosis infections

Radioimmunotherapy as a pathogen-agnostic treatment method for opportunistic mucormycosis infections

Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives

A novel radiolabelled salmochelin derivative for bacteria-specific PET imaging: synthesis, radiolabelling and evaluation

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