The many roads to infection imaging

Welling, Mick M.; Stokkel, Marcel P. M.; Balter, Jenny; Sarda‐Mantel, Laure; Meulemans, A.; Guludec, Dominique Le

doi:10.1007/s00259-007-0695-8

Cited by 23 publications

(15 citation statements)

References 10 publications

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“…For example, 99m Tc-ciprofloxacin was evaluated in a clinical study for diagnosing infections (12), but follow-up studies demonstrated nonspecific binding, and an inability to differentiate infection from sterile inflammation (13,14). Radiolabeled peptides have shown promise in preclinical models (15,16), but lack mechanistic binding or uptake, which could limit generalizability (17). In addition, 124 I-FIAU, a nucleoside analog substrate for thymidine kinase, has been described as a γ-herpesvirus and bacteria-selective tracer (18).…”

Section: Discussionmentioning

confidence: 99%

A Systematic Approach for Developing Bacteria-Specific Imaging Tracers

et al. 2016

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The modern patient is increasingly susceptible to bacterial infections including those due to multi-drug resistant organisms (MDROs). Noninvasive whole-body analysis with pathogen-specific imaging technologies can significantly improve patient outcomes by rapidly identifying a source of infection and monitoring the response to treatment, but no such technology exists clinically. Methods We systematically screened 961 random, radiolabeled molecules in silico as substrates for essential metabolic pathways in bacteria, followed by in vitro uptake in representative bacteria – Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and mycobacteria. Fluorine-labeled analogs, that could be developed as positron emission tomography (PET)-based imaging tracers, were evaluated in a murine myositis model. Results We identified three novel, non-toxic molecules demonstrating selective bacterial uptake: para-aminobenzoic acid (PABA), with uptake in all representative bacteria including Mycobacterium tuberculosis; mannitol, with selectively uptake in S. aureus and E. coli; and sorbitol, accumulating only in E. coli. None accumulated in mammalian cells or heat-killed bacteria, suggesting metabolism-derived specificity. In addition to an extended bacterial panel of laboratory strains, all three molecules rapidly accumulated in respective clinical isolates of interest including MDROs such as methicillin resistant S. aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing, and carbapenem-resistant Enterobacteriaceae. In a murine myositis model, fluorine-labeled analogs of all three molecules could rapidly detect and differentiate infection sites from sterile inflammation in mice (P=0.03). Finally, 2-deoxy-2-[F-18]fluoro-D-sorbitol (18F-FDS) can be easily synthesized from 2-deoxy-2-[F-18]fluoro-D-glucose (18F-FDG). PET, utilizing 18F-FDS synthesized using current good manufacturing practice, could rapidly differentiate true infection from sterile inflammation to selectively localize E. coli infection in mice. Conclusion We have developed a systematic approach that exploits unique biochemical pathways in bacteria to develop novel pathogen-specific imaging tracers. These tracers have significant potential for clinical translation to specifically detect and localize a broad range of bacteria, including MDROs.

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Section: Discussionmentioning

confidence: 99%

A Systematic Approach for Developing Bacteria-Specific Imaging Tracers

et al. 2016

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“…For example, combined radiolabelled 111 In-leukocytes and 99m Tc-MDP-SPECT of osteomyelitis, both non-specific tracers, already presented a sensitivity of 95% and a specificity of 93% [33]. Possible explanations for these unsatisfactory results, which limits its widespread clinical applicability, include radiochemical impurities, nonspecific binding and high efflux from the site of infection [34][35][36][37].…”

Section: Bacterial Infection Imaging Agents Based On Antibioticsmentioning

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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“…The most extensively investigated of these compounds is the 4-fluoroquinolone antibiotic, ciprofloxacin, a broad spectrum antibiotic that inhibits the actions of DNA gyrase in gram-negative bacteria and type IV topoisomerase in gram-positive bacteria, resulting in rapid bacterial death. 99m Tc-ciprofloxacin ( 99m Tc-cipro) has been investigated extensively for diagnosing a variety of infections, and the results are inconclusive [6,20,68,74,91]. The limited data on its value in SI also are inconclusive [11,23].…”

Section: Radiolabeled Ciprofloxacinmentioning

confidence: 99%

Expanding role of 18F-fluoro-d-deoxyglucose PET and PET/CT in spinal infections

et al. 2010

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(18)F-fluoro-D -deoxyglucose positron emission tomography ([(18)F]-FDG PET) is successfully employed as a molecular imaging technique in oncology, and has become a promising imaging modality in the field of infection. The non-invasive diagnosis of spinal infections (SI) has been a challenge for physicians for many years. Morphological imaging modalities such as conventional radiography, computed tomography (CT), and magnetic resonance imaging (MRI) are techniques frequently used in patients with SI. However, these methods are sometimes non-specific, and difficulties in differentiating infectious from degenerative end-plate abnormalities or postoperative changes can occur. Moreover, in contrast to CT and MRI, FDG uptake in PET is not hampered by metallic implant-associated artifacts. Conventional radionuclide imaging tests, such as bone scintigraphy, labeled leukocyte, and gallium scanning, suffer from relatively poor spatial resolution and lack sensitivity, specificity, or both. Initial data show that [(18)F]-FDG PET is an emerging imaging technique for diagnosing SI. [(18)F]-FDG PET appears to be especially helpful in those cases in which MRI cannot be performed or is non-diagnostic, and as an adjunct in patients in whom the diagnosis is inconclusive. The article reviews the currently available literature on [(18)F]-FDG PET and PET/CT in the diagnosis of SI.

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The many roads to infection imaging

Cited by 23 publications

References 10 publications

A Systematic Approach for Developing Bacteria-Specific Imaging Tracers

A Systematic Approach for Developing Bacteria-Specific Imaging Tracers

An update on radiotracer development for molecular imaging of bacterial infections

Expanding role of 18F-fluoro-d-deoxyglucose PET and PET/CT in spinal infections

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