Synthesis, in vitro evaluation, and <sup>68</sup>Ga‐radiolabeling of <scp>CDP</scp>1 toward <scp>PET</scp>/<scp>CT</scp> imaging of bacterial infection

Dutta, Jyotibon; Baijnath, Sooraj; Somboro, Anou M.; Nagiah, Savania; Alberício, Fernando; Torre, Beatriz G. de la; Marjanovic-Painter, Biljana; Zeevaart, Jan Rijn; Sathekge, Mike; Kruger, Hendrik G.; Chuturgoon, Anil A.; Naicker, Tricia; Ebenhan, Thomas; Govender, Thavendran

doi:10.1111/cbdd.12980

Cited by 10 publications

(8 citation statements)

References 42 publications

(67 reference statements)

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“…The hybrid imaging approach for imaging of deep infections it is postulated, when combined with a radioisotope, sites of infection can be identified using non-invasive nuclear imaging techniques and guide the subsequent surgical intervention and fluorescence guided surgery [74,75]. Research with other AMPs for pre-clinical imaging of infections is still ongoing [52,[76][77][78][79]. Recently, a synthetic analogue of the natural cyclic antimicrobial peptide depsidomycin ( 68 Ga-DOTA-TBIA101, Scheme 5), was investigated for its characteristic to target bacteria.…”

Section: Imaging Of Infections With Antimicrobial Peptidesmentioning

confidence: 99%

An update on radiotracer development for molecular imaging of bacterial infections

Welling

Hensbergen

Bunschoten

et al. 2019

Clin Transl Imaging

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Background Bacterial infections are still a major global healthcare problem. To combat the increasing antimicrobial resistance, early diagnosis of bacterial infections-including the identification of bacterial species-is needed to improve antibiotic stewardship and to help reduce the use of broad-spectrum antibiotics. To aid successful targeted antibiotic treatment, specific detection and localisation of infectious organisms is warranted. Nuclear medicine imaging approaches have been successfully used to diagnose bacterial infections and to differentiate between pathogen induced infections and sterile inflammatory processes. Aim In this comprehensive review we present an overview of recent developments in radiolabelled bacterial imaging tracers. Methods The PubMed/MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on specific imaging of bacterial using specific guidelines with MeSH-terms, truncations, and completion using cross-references. Tracers in literature that was extensively reviewed before 2016 were not included in this update. Where possible, the chemical structure of the radiolabelled compounds and clinical images were shown. Results In 219 original articles pre-clinical and clinical imaging of bacterial infection with new tracers were included. In our view, the highest translational potential lies with tracers that are specific to target the pathogens: e.g., 99m Tc-and 68 Galabelled UBI 29-41 , 99m Tc-vancomycin, m-[ 18 F]-fluoro-PABA, [methyl-11 C]-D-methionine, [ 18 F]-FDS, [ 18 F]-maltohexaose and [ 18 F]-maltotriose. An encouraging note is that some of these tracers have already been successfully evaluated in clinical settings. Conclusion This review summarises updates in tracer development for specific (pre-clinical and clinical) imaging of bacterial infections. We propsed some promising tracers that are likely to become innovative standards in the clinical setting in the near feature.

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Section: Imaging Of Infections With Antimicrobial Peptidesmentioning

confidence: 99%

An update on radiotracer development for molecular imaging of bacterial infections

Welling

Hensbergen

Bunschoten

et al. 2019

Clin Transl Imaging

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“…100 In 2017, Dutta et al radiolabeled and reported LL37, a human cathelicidin antimicrobial peptide ( 68 Ga-CDP1) that had higher uptake in in vitro bacterial cultures of S. aureus , E. coli and M. smegmatis , compared to eukaryotic cells. 101 Additional not bacteria-specific radiolabeled peptides such as the human neutrophil peptide ( 99m Tc-HNP-1), neutrophil elastase inhibitor peptide ( 99m Tc-HNE-2), human β-defensin ( 99m Tc-HBD-3), and vascular adhesion protein-1 selective peptide ( 68 Ga-DOTAVAP-P1), have been evaluated for bacterial imaging with variable results. 102–105…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

Pathogen-Specific Bacterial Imaging in Nuclear Medicine

Ordoñez

Jain

2018

Seminars in Nuclear Medicine

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When serious infections are suspected, patients are often treated empirically with broad-spectrum antibiotics while awaiting results that provide information on the bacterial class and species causing the infection, as well as drug susceptibilities. For deep-seated infections, these traditional diagnostic techniques often rely on tissue biopsies to obtain clinical samples which can be expensive, dangerous, and has the potential of sampling bias. Moreover, these procedures and results can take several days and may not always provide reliable information. This combination of time and effort required for proper antibiotic selection has become a barrier leading to indiscriminate broad-spectrum antibiotic use. Exposure to nosocomial infections and indiscriminate use of broad-spectrum antibiotics are responsible for promoting bacterial drug-resistance leading to substantial morbidity and mortality, especially in hospitalized and immunosuppressed patients. Therefore, early diagnosis of infection and targeted antibiotic treatments are urgently needed to reduce morbidity and mortality caused by bacterial infections worldwide. Reliable pathogen-specific bacterial imaging techniques have the potential to provide early diagnosis and guide antibiotic treatments.

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“…Although metabolic agents and radiolabeled sugars have shown potential in small animal trials and with a few bacterial species, they do not seem to have the same broad-spectrum bacterial affinity as TMP and have a significant background uptake of normal tissues [ 86 , 97 , 98 , 99 ].…”

Section: Specific Radiotracers Studied For Direct Visualization Of Ba...mentioning

confidence: 99%

Is Imaging Bacteria with PET a Realistic Option or an Illusion?

et al. 2023

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The application of [18F]-fluorodeoxyglucose ([18F]FDG) as a radiotracer to detect sites of inflammation (either due to bacterial infection or primary inflammation) has led to exploring the role of PET in visualizing bacteria directly at sites of infection. However, the results from such efforts are controversial and inconclusive so far. We aimed to assess the limitations of PET as an effective modality in the diagnosis of bacterial infections. Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable to visualize bacteria as the underlying cause of inflammation. Hence, more specific radiotracers that possibly bind to or accumulate in bacteria-specific receptors or enzymes are being explored. Several radiotracers, including 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS), 6-[18F]-fluoromaltose, [11C]para-aminobenzoic acid ([11C]PABA), radiolabeled trimethoprim (11C-TMP) and its analog fluoropropyl-trimethoprim (18F-FPTMP), other radiolabeled sugars, and antimicrobial drugs have been used to image microorganisms. Unfortunately, no progress has been made in translating the results to routine human use; feasibility and other factors have constrained their success in clinical settings. In the current article, we discuss the limitations of direct bacterial visualization with PET tracers, but emphasize the important role of [18F]FDG-PET as the only option for detecting evidence of infection.

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Synthesis, in vitro evaluation, and ⁶⁸Ga‐radiolabeling of CDP1 toward PET/CT imaging of bacterial infection

Cited by 10 publications

References 42 publications

An update on radiotracer development for molecular imaging of bacterial infections

An update on radiotracer development for molecular imaging of bacterial infections

Pathogen-Specific Bacterial Imaging in Nuclear Medicine

Is Imaging Bacteria with PET a Realistic Option or an Illusion?

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Synthesis, in vitro evaluation, and 68Ga‐radiolabeling of CDP1 toward PET/CT imaging of bacterial infection

Cited by 10 publications

References 42 publications

An update on radiotracer development for molecular imaging of bacterial infections

An update on radiotracer development for molecular imaging of bacterial infections

Pathogen-Specific Bacterial Imaging in Nuclear Medicine

Is Imaging Bacteria with PET a Realistic Option or an Illusion?

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Product

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Synthesis, in vitro evaluation, and ⁶⁸Ga‐radiolabeling of CDP1 toward PET/CT imaging of bacterial infection