68Ga-NOTA-ubiquicidin fragment for PET imaging of infection: From bench to bedside

Mukherjee, Archana; Bhatt, Jyotsna; Shinto, Ajit; Korde, Aruna; Kumar, Mukesh; Kamaleshwaran, Koramadai Karuppusamy; Joseph, Jephy; Sarma, Haladhar Dev; Dash, Ashutosh

doi:10.1016/j.jpba.2018.06.064

Cited by 24 publications

(26 citation statements)

References 26 publications

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“…From preclinical studies in vivo it has been shown that 99m Tc-UBI 29-41 (coordination unknown) and 99m Tc-HYNIC UBI 29-41 (Scheme 4) accumulated specifically in infected tissues with abscessto-muscle ratios between 2 and 3 [14,56,57]. Both recently developed PET analogues 68 Ga-NOTA-UBI 29-41 [12,[58][59][60][61] and 68 Ga-NOTA-UBI 31-38 [62] showed comparable uptake characteristics in infected thigh muscles in mice and rabbits. However, UBI 29-41 also accumulated in infections with the yeast C. albicans [63], which reduces specificity of this tracer for imaging of bacterial infections alone.…”

Section: Imaging Of Infections With Antimicrobial Peptidesmentioning

confidence: 99%

“…A pooled meta-analysis of clinical studies with 99m Tc-UBI 29-41 showed 95% sensitivity, 93% specificity and 94% accuracy in various clinical settings including prosthetic infections, diabetic foot infections, fever of unknown origin, osteomyelitis, mediastinitis, and appendicitis [55,64,65]. Due to its ability to discriminate between infection and sterile inflammation, general safety, the lack of side effects [66][67][68][69], and the successful transformation to kit formulations [59,[70][71][72], radiolabelled UBI 29-41 has been proposed as a good candidate for applications in routine imaging [4,9,61]. Nevertheless, prospective multi-centre studies of both 99m Tc-and 68 Ga-UBI 29-41 should still be carried out to achieve robust evidence of the accuracy in clinical imaging of bacterial infections.…”

Section: Imaging Of Infections With Antimicrobial Peptidesmentioning

confidence: 99%

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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%

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

View full text Add to dashboard Cite

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“…In addition, following the experience of 68 Ga-radiolabeled antimicrobial peptides [5,[45][46][47] and considering the fast binding of PMB to bacteria and fast metabolic clearance, we may consider labeling PMB with 68 Ga for PET applications.…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Evaluation of 99mTc-Polymyxin B for Specific Targeting of Gram-Bacteria

et al. 2021

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Background: Infectious diseases are one of the main causes of morbidity and mortality worldwide. Nuclear molecular imaging would be of great help to non-invasively discriminate between septic and sterile inflammation through available radiopharmaceuticals, as none is currently available for clinical practice. Here, we describe the radiolabeling procedure and in vitro and in vivo studies of 99mTc-polymyxin B sulfate (PMB) as a new single photon emission imaging agent for the characterization of infections due to Gram-negative bacteria. Results: Labeling efficiency was 97 ± 2% with an average molar activity of 29.5 ± 0.6 MBq/nmol. The product was highly stable in saline and serum up to 6 h. In vitro binding assay showed significant displaceable binding to Gram-negative bacteria but not to Gram-positive controls. In mice, 99mTc-HYNIC-PMB was mainly taken up by liver and kidneys. Targeting studies confirmed the specificity of 99mTc-HYNIC-PMB obtained in vitro, showing significantly higher T/B ratios for Gram-negative bacteria than Gram-positive controls. Conclusions: In vitro and in vivo results suggest that 99mTc-HYNIC-PMB has a potential for in vivo identification of Gram-negative bacteria in patients with infections of unknown etiology. However, further investigations are needed to deeply understand the mechanism of action and behavior of 99mTc-HYNIC-PMB in other animal models and in humans.

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“…As for SPET, a number of PET studies are ongoing concerning the labelling and initial clinical use of AMPs [123][124][125] mainly labeled with 68 Ga. Although preliminary AMPs seems very promising in differentiating inflammation and infection.…”

Section: Other Pet/ct Tracersmentioning

confidence: 99%

Molecular Imaging of Pulmonary Inflammation and Infection

Giraudo

Evangelista

Fraia

et al. 2020

IJMS

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Infectious and inflammatory pulmonary diseases are a leading cause of morbidity and mortality worldwide. Although infrequently used in this setting, molecular imaging may significantly contribute to their diagnosis using techniques like single photon emission tomography (SPET), positron emission tomography (PET) with computed tomography (CT) or magnetic resonance imaging (MRI) with the support of specific or unspecific radiopharmaceutical agents. 18F-Fluorodeoxyglucose (18F-FDG), mostly applied in oncological imaging, can also detect cells actively involved in infectious and inflammatory conditions, even if with a low specificity. SPET with nonspecific (e.g., 67Gallium-citrate (67Ga citrate)) and specific tracers (e.g., white blood cells radiolabeled with 111Indium-oxine (111In) or 99mTechnetium (99mTc)) showed interesting results for many inflammatory lung diseases. However, 67Ga citrate is unfavorable by a radioprotection point of view while radiolabeled white blood cells scan implies complex laboratory settings and labeling procedures. Radiolabeled antibiotics (e.g., ciprofloxacin) have been recently tested, although they seem to be quite unspecific and cause antibiotic resistance. New radiolabeled agents like antimicrobic peptides, binding to bacterial cell membranes, seem very promising. Thus, the aim of this narrative review is to provide a comprehensive overview about techniques, including PET/MRI, and tracers that can guide the clinicians in the appropriate diagnostic pathway of infectious and inflammatory pulmonary diseases.

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68Ga-NOTA-ubiquicidin fragment for PET imaging of infection: From bench to bedside

Cited by 24 publications

References 26 publications

An update on radiotracer development for molecular imaging of bacterial infections

An update on radiotracer development for molecular imaging of bacterial infections

In Vitro and In Vivo Evaluation of 99mTc-Polymyxin B for Specific Targeting of Gram-Bacteria

Molecular Imaging of Pulmonary Inflammation and Infection

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