67 Ga-labeled deferoxamine derivatives for imaging bacterial infection: Preparation and screening of functionalized siderophore complexes

Ioppolo, Joseph A.; Caldwell, Deanna; Beiraghi, Omid; Llano, Lisset; Blacker, Megan; Valliant, John F.; Berti, Paul J.

doi:10.1016/j.nucmedbio.2017.05.010

Cited by 33 publications

(26 citation statements)

References 48 publications

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“…Recent studies have shown bacterial uptake of radiolabelled sugars and sugar alcohols that are not efficiently metabolized by humans, such as 2-deoxy-2-[ 18 F]fluorosorbitol ( 18 F-FDS), 6-[ 18 F]fluoromaltose, and 6″-[ 18 F]fluoromaltotriose 10–12 . Other innovative approaches target bacterial iron metabolism via 67 Ga or 68 Ga-siderophore complexes 13–15 . Recently we also showed that a D-amino acid derived tracer D-[methyl- 11 C]methionine ([ 11 C]D-Met) could distinguish active infection from sterile inflammation in a murine myositis model, presumably via incorporation into bacterial peptidoglycan 16 .…”

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confidence: 99%

[¹¹C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

et al. 2018

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Imaging studies are frequently used to support the clinical diagnosis of infection. These techniques include computed tomography (CT) and magnetic resonance imaging (MRI) for structural information, and single photon emission computed tomography (SPECT) or positron emission tomography (PET) for metabolic data. However, frequently there is significant overlap in the imaging appearance of infectious and non-infectious entities using these tools. To address this concern, recent approaches have targeted bacteria-specific metabolic pathways. For example, radiolabelled sugars derived from sorbitol and maltose have been investigated as PET radiotracers, since these are efficiently incorporated into bacteria but are poor substrates for mammalian cells. We have previously shown that para-aminobenzoic acid (PABA) is an excellent candidate for development as a bacteria-specific imaging tracer as it is rapidly accumulated by a wide range of pathogenic bacteria, including metabolically quiescent bacteria and clinical strains, but not by mammalian cells. Therefore, in this study we developed an efficient radiosynthesis for [11C]PABA, investigated its accumulation into Escherichia coli and Staphylococcus aureus laboratory strains in vitro, and shown that it can distinguish between infection and sterile inflammation in a murine model of acute bacterial infection.

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confidence: 99%

[¹¹C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

et al. 2018

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“…fialuridine), saccharides (e.g. fluorodeoxysorbitol, maltohexaose, maltose, trehalose), oligomers, polyethyleneglycol liposomes, fluorophores and siderophores 18 , 20 – 22 . However, none of these probes was translated to routine clinical practice so far.…”

Section: Discussionmentioning

confidence: 99%

“…Radiolabelling of siderophores can be achieved easily by replacing Fe 3+ in the siderophore by a suitable radionuclide 15 , 25 . There is no isotope of iron with suitable properties for imaging in terms of half-life and photon emission, however, Ga 3+ is an isosteric diamagnetic substitute for Fe 3+ and has been used extensively to characterize siderophore complexes 15 , 22 . Recently, interest in the isotope Ga-68, a positron emitter, has increased tremendously with the establishment of PET as a clinical imaging modality.…”

Section: Discussionmentioning

confidence: 99%

“…Radiolabelled siderophores have been investigated in radiopharmaceutical research already in early 1980s 28 , 29 and recently were successfully used for the detection of Staphylococcus aureus infection 22 and for preclinical imaging of Invasive Aspergillosis (IA) caused by the fungal pathogen Aspergillus fumigatus 16 , 17 . Triacetylfusarinine C (TAFC), siderophore produced by A. fumigatus , was labelled with Ga-68 with high affinity and stability.…”

Section: Discussionmentioning

confidence: 99%

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Imaging of Pseudomonas aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography

Petřík

Umlaufova

Raclavsky

et al. 2018

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Pseudomonas aeruginosa is an increasingly prevalent opportunistic pathogen that causes a variety of life-threatening nosocomial infections. Novel strategies for the development of new antibacterial treatments as well as diagnostic tools are needed. One of the novel diagnostic strategies for the detection of infection could be the utilization of siderophores. Siderophores are low-molecular-weight chelators produced by microbes to scavenge essential iron. Replacing iron in siderophores by suitable radiometals, such as Ga-68 for positron emission tomography (PET) imaging, opens approaches for targeted imaging of infection. Here we report on pyoverdine PAO1 (PVD-PAO1), a siderophore produced by P. aeruginosa, labelled with Ga-68 for specific imaging of Pseudomonas infections. PVD-PAO1 was labelled with Ga-68 with high radiochemical purity. The resulting complex showed hydrophilic properties, low protein binding and high stability in human serum. In vitro uptake of 68Ga-PVD-PAO1 was highly dependent on the type of microbial culture. In normal mice 68Ga-PVD-PAO1 showed rapid pharmacokinetics with urinary excretion. PET imaging in infected animals displayed specific accumulation of 68Ga-PVD-PAO1 in infected tissues and better distribution than clinically used 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-citrate. Ga-68 labelled pyoverdine PAO1 seems to be a promising agent for imaging of P. aeruginosa infections by means of PET.

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“…Vorster et al recently described its use in imaging infection and inflammation (33). A derivative of deferoxamine was successfully labeled with 67 Ga and was shown to localize at the site of Staphylococcus aureus infection (34).…”

Section: Imaging Microbial Iron Metabolism: Radiolabeled Siderophoresmentioning

confidence: 99%

Metabolic Imaging of Infection

et al. 2017

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Metabolic imaging has come to occupy a prominent place in the diagnosis and management of microbial infection. Molecular probes available for infection imaging have undergone a rapid evolution starting with nonspecific agents that accumulate similarly in infection, sterile inflammation, and neoplastic tissue and then extending to more targeted probes that seek to identify specific microbial species. This focus review describes the metabolic and molecular imaging techniques currently available for clinical use in infection imaging and those that have demonstrated promising results in preclinical studies with the potential for clinical applications.

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67 Ga-labeled deferoxamine derivatives for imaging bacterial infection: Preparation and screening of functionalized siderophore complexes

Cited by 33 publications

References 48 publications

[¹¹C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

[¹¹C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

Imaging of Pseudomonas aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography

Metabolic Imaging of Infection

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67 Ga-labeled deferoxamine derivatives for imaging bacterial infection: Preparation and screening of functionalized siderophore complexes

Cited by 33 publications

References 48 publications

[11C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

[11C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

Imaging of Pseudomonas aeruginosa infection with Ga-68 labelled pyoverdine for positron emission tomography

Metabolic Imaging of Infection

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Product

Resources

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[¹¹C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism

[¹¹C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism