Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives

Dadachova, Ekaterina; Rangel, Drauzio E.N.

doi:10.3389/fmed.2022.819702

Cited by 13 publications

(8 citation statements)

References 57 publications

(80 reference statements)

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“…The latest developments in infection imaging with radiopharmaceuticals have recently been highlighted [26]. In order to improve the theranostic approach even further, smaller vehicles can be used, such as small proteins, nanobodies, such as heavy chain (VHH), or other single domain antibodies or peptides [27,28].…”

Section: Discussionmentioning

confidence: 99%

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

Dijk

Duyvenbode

Vor

et al. 2023

IJMS

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Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus 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 111In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus 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 111In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm3 at 24 h to 9.22 %ID/cm3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm3, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm3 at 120 h. The effective half-life of 111In-4497 mAbs was determined to be 59 h. In conclusion, 111In-4497 mAbs were found to specifically detect S. aureus 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.

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Section: Discussionmentioning

confidence: 99%

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

Dijk

Duyvenbode

Vor

et al. 2023

IJMS

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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][38][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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“…However, molecular imaging with the use of nuclear medicine reflects pathophysiological processes and changes, allowing early detection and localisation of infection and inflammatory processes, as well as accurate monitoring of treatment response (Holcman et al 2023 ; Jasińska et al 2022 ; Albano et al 2020 ; Giraudo et al 2020 ; Palestro 2019 , 2020 ; Meyer et al 2019 ; Kleynhans et al 2023 ; Signore et al 2023 ; Glaudemans and Gheysens 2023 ; Pijl et al 2021 ; Seltzer et al 2019 ). Since the discovery of gallium-67 for medical use in the 1940s (Dittrich and Jesus 2022 ) and, later on, autologous leukocytes radiolabelled with indium-111, reported for the first time in 1976 (Segal et al 1976 ), and technetium-99m, a few years later, for infection imaging, there has been a continuous search for more bacteria-specific radiopharmaceuticals to be utilised for infection imaging (Akter et al 2023 ; Palestro 2019 ; Glaudemans and Gheysens 2023 ; Gouws et al 2022 ; Pijl et al 2021 ; Dadachova and Rangel 2022 ; Signore et al 2022 ; Koźmiński et al 2021 ). Conventional infection imaging agents (such as [ 67 Ga]Ga-citrate, [ 111 In]In-oxine- or [ 99m Tc]Tc-HMPAO-labelled leukocytes, and [ 18 F]FDG) do not target bacteria, but rather the host immune response to the bacterial infection, and will therefore also localise in sterile inflammatory foci.…”

Section: Introductionmentioning

confidence: 99%

Recently developed radiopharmaceuticals for bacterial infection imaging

Kahts,

Summers,

Gutta

et al. 2024

EJNMMI radiopharm. chem.

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Background Infection remains a major cause of morbidity and mortality, regardless of advances in antimicrobial therapy and improved knowledge of microorganisms. With the major global threat posed by antimicrobial resistance, fast and accurate diagnosis of infections, and the reliable identification of intractable infection, are becoming more crucial for effective treatment and the application of antibiotic stewardship. Molecular imaging with the use of nuclear medicine allows early detection and localisation of infection and inflammatory processes, as well as accurate monitoring of treatment response. There has been a continuous search for more specific radiopharmaceuticals to be utilised for infection imaging. This review summarises the most prominent discoveries in specifically bacterial infection imaging agents over the last five years, since 2019. Main body Some promising new radiopharmaceuticals evaluated in patient studies are reported here, including radiolabelled bacterial siderophores like [68Ga]Ga-DFO-B, radiolabelled antimicrobial peptide/peptide fragments like [68Ga]Ga-NOTA-UBI29-41, and agents that target bacterial synthesis pathways (folic acid and peptidoglycan) like [11C]para-aminobenzoic acid and D-methyl-[11C]-methionine, with clinical trials underway for [18F]fluorodeoxy-sorbitol, as well as for 11C- and 18F-labelled trimethoprim. Conclusion It is evident that a great deal of effort has gone into the development of new radiopharmaceuticals for infection imaging over the last few years, with remarkable progress in preclinical investigations. However, translation to clinical trials, and eventually clinical Nuclear Medicine practice, is apparently slow. It is the authors’ opinion that a more structured and harmonised preclinical setting and well-designed clinical investigations are the key to reliably evaluate the true potential of the newly proposed infection imaging agents.

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Highlights of the Latest Developments in Radiopharmaceuticals for Infection Imaging and Future Perspectives

Cited by 13 publications

References 57 publications

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

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

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

Recently developed radiopharmaceuticals for bacterial infection imaging

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