Radiosynthesis and pre-clinical evaluation of [ Ga] labeled antimicrobial peptide fragment GF-17 as a potential infection imaging PET radiotracer

Chopra, Seema; Singh, Baljinder; Koul, Ashwani; Mishra, Anil K.; Robu, Stephanie; Kaur, Amritjyot; Ghai, Anchal; Caplash, Neena; Wester, Hans‐Jürgen

doi:10.1016/j.apradiso.2019.04.008

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…The pilot study showed a modest T/NT of 2.5, while further studies have shown a T/NT of up to 5.7. Furthermore, 99m Tc-labeled HBD-3 was able to discriminate S. aureus infection from sterile inflammation [72,73,74] This again supports that chelated probes may be especially well suited for extracellular targets.…”

Section: Extracellular Targetsmentioning

confidence: 83%

Radiochemical Approaches to Imaging Bacterial Infections: Intracellular versus Extracellular Targets

Northrup

Mach

Sellmyer

2019

IJMS

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The discovery of penicillin began the age of antibiotics, which was a turning point in human healthcare. However, to this day, microbial infections are still a concern throughout the world, and the rise of multidrug-resistant organisms is an increasing challenge. To combat this threat, diagnostic imaging tools could be used to verify the causative organism and curb inappropriate use of antimicrobial drugs. Nuclear imaging offers the sensitivity needed to detect small numbers of bacteria in situ. Among nuclear imaging tools, radiolabeled antibiotics traditionally have lacked the sensitivity or specificity necessary to diagnose bacterial infections accurately. One reason for the lack of success is that the antibiotics were often chelated to a radiometal. This was done without addressing the ramifications of how the radiolabeling would impact probe entry to the bacterial cell, or the mechanism of binding to an intracellular target. In this review, we approach bacterial infection imaging through the lens of bacterial specific molecular targets, their intracellular or extracellular location, and discuss radiochemistry strategies to guide future probe development.

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Section: Extracellular Targetsmentioning

confidence: 83%

Radiochemical Approaches to Imaging Bacterial Infections: Intracellular versus Extracellular Targets

Northrup

Mach

Sellmyer

2019

IJMS

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“…However, larger clinical studies are needed for their translation to routine Nuclear Medicine practice (Kleynhans et al 2023). Chopra et al (2019) synthesised GF-17, an AMP fragment corresponding to residues 17 to 32 of human antibacterial cathelicidin (LL-37), that was functionalised with [ 68 Ga] Ga-DOTA. The radiolabelling parameters were optimised (pH of 4, DOTA-GF-17 = 20 nmol, 95 °C for 30 min) to deliver a labelling efficiency of ≥ 95%.…”

Section: Ga-labelled Antimicrobial Peptide Fragmentsmentioning

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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“…It has been labeled with 99m Tc via hydrazinonicotinamide (HYNIC) or other chelating agents to enable SPECT imaging (31,32) but relatively recent availability of PET-enabling 68 Ga has made the labeling with the latter supplanting other radionuclides due to the good match between short physical half-life of 68 Ga (68 min) and short plasma half-life of ubiquicidin and other AMPs (33,34). Other recently described AMPs-radionuclide combinations include [ 99m Tc-HYNIC/EDDA]-MccJ25 (35); 99m Tc-human beta-defensin 3 (HBD-3) (36); 64 Cu-labeled cationic peptides HLys-DOTA, synthesized as the D-isomer and AB1-HLys-DOTA, synthesized with an unnatural aminoacid to slow down the blood clearance (37); and 68 Ga-DOTA-CF-17 (38).…”

Section: Imaging Bacterial Infections With Radiolabeled Antibiotics S...mentioning

confidence: 99%

“…The advantage of AMPs over radiolabeled antibiotics is that AMP are larger molecules which should allow attachment of radiolabels without loss of the ability to bind bacteria in a specific manner; the disadvantage is their fast blood clearance due to enzymatic destruction and also high kidney uptake. Evaluation of AMPs in murine models of S. aureus (34,(36)(37)(38), mice with E. coli infection (35), P. aeruginosa (38) demonstrated the highest target to non-target ratios of 2-6 reached from 45 to 120 min post administration of radiolabeled peptides, showing their ability to distinguish the infected tissues from sterile inflammation. Auletta et al performed side by side comparison of 99m Tc-Ubiquicidin 29-41, 99m Tc-ciprofloxacin and 99m Tc-ciprofloxacin dithiocarbamate (CS2) in vitro and in mice with S. aureus and E.coli infections (32).…”

Section: Imaging Bacterial Infections With Radiolabeled Antibiotics S...mentioning

confidence: 99%

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

Dadachova

Rangel

2022

Front. Med.

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COVID-19 pandemic has heightened the interest toward diagnosis and treatment of infectious diseases. Nuclear medicine with its powerful scintigraphic, single photon emission computer tomography (SPECT) and positron emission tomography (PET) imaging modalities has always played an important role in diagnosis of infections and distinguishing them from the sterile inflammation. In addition to the clinically available radiopharmaceuticals there has been a decades-long effort to develop more specific imaging agents with some examples being radiolabeled antibiotics and antimicrobial peptides for bacterial imaging, radiolabeled anti-fungals for fungal infections imaging, radiolabeled pathogen-specific antibodies and molecular engineered constructs. In this opinion piece, we would like to discuss some examples of the work published in the last decade on developing nuclear imaging agents for bacterial, fungal, and viral infections in order to generate more interest among nuclear medicine community toward conducting clinical trials of these novel probes, as well as toward developing novel radiotracers for imaging infections.

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Radiosynthesis and pre-clinical evaluation of [ Ga] labeled antimicrobial peptide fragment GF-17 as a potential infection imaging PET radiotracer

Cited by 7 publications

References 28 publications

Radiochemical Approaches to Imaging Bacterial Infections: Intracellular versus Extracellular Targets

Radiochemical Approaches to Imaging Bacterial Infections: Intracellular versus Extracellular Targets

Recently developed radiopharmaceuticals for bacterial infection imaging

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

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