Preclinical Research Highlighting Contemporary Targeting Mechanisms of Radiolabelled Compounds for PET Based Infection Imaging

Kleynhans, Janke; Sathekge, Mike; Ebenhan, Thomas

doi:10.1053/j.semnuclmed.2023.03.001

Cited by 12 publications

(35 citation statements)

References 105 publications

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“…However, the group did not further pursue the in vivo biodistribution investigations of the probe. 67,69 Based on these promising results, for the first time, an 18 F-labeled alanine derivative (D-[ 18 F-CF 3 ]alanine) was reported for infection imaging. Unfortunately, the probe performed less than expected, with low specific activity and bacterial incorporation.…”

Section: Emerging Radiotracers Targeting Peptidoglycan Biosynthesismentioning

confidence: 99%

“…However, this study further synthesized (R)-2-amino-3-(4-[ 18 F]fluorophenyl)propanoic acid, an analog of D-Phe by substitution of a proton with [ 18 F], to test the changes in bacterial uptake studies. 73 According to the results, the replacement of 14 C with 18 F did not affect the uptake of D-Phe, and a significant specificity (>14-fold higher than [ 18 targeting, which warrants further investigation in mouse infection models and PET/CT imaging. In many Gram-positive strains, D-glutamate is converted to D-glutamine (D-Gln) at glutaminase's second position of the peptidoglycan precursor.…”

Section: Emerging Radiotracers Targeting Peptidoglycan Biosynthesismentioning

confidence: 99%

“…A study by Hu et al 113 revealed that hydroxyl groups are essential for binding GlcNAc to MurG. Therefore, the 18 Facetyl conjugation strategy did not affect the binding properties of [ 18 F]FAG. This might be due to the acetyl group's inability to participate in the binding interface of MurG, as previously reported, allowing the synthesis of [ 18 F]FAG-containing lipid II for ultimate incorporation into peptidoglycan; however, more work is required to solidify the route of incorporation.…”

Section: Park's Nucleotide and Lipid-basedmentioning

confidence: 99%

“…Unlike [ 18 F]FAG which is metabolized by mammalian cells, 119 a MurNAc-based radiolabeled probe will potentially increase the specificity and selectivity of the bacterial foci, as it is unique to bacteria. A plausible radiolabeling strategy could be explored with tolerated modifications at the N-acetyl terminus of the MurNAc residue using 18 F-or 11 C-labeling, enabling targeting and imaging of peptidoglycan biosynthesis using PET/CT. 118 3.5.…”

Section: Park's Nucleotide and Lipid-basedmentioning

confidence: 99%

“…This setting will require the integration of advanced techniques with high sensitivity, such as polyacrylamide high-pressure liquid chromatography (HPLC), polyacrylamide gel electrophoresis, autoradiography, mass spectrometry, and nuclear magnetic resonance (NMR). 37,104,146−148 Once potential derivatives specific to the peptidoglycan metabolism have been identified, they can be optimized for 18 F-and 11 C-radiosynthesis, followed by in vitro uptake using bacterial strain mutants of the enzymes involved in the metabolic process of interest as negative controls. This can be achieved through genetic manipulation or the use of targeted peptidoglycan inhibitors, such as antibiotics.…”

Section: Design Approach and Challenges For Translationmentioning

confidence: 99%

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Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives

Koatale,

Welling,

Ndlovu

et al. 2024

ACS Infect. Dis.

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The unique structural architecture of the peptidoglycan allows for the stratification of bacteria as either Gram-negative or Gram-positive, which makes bacterial cells distinguishable from mammalian cells. This classification has received attention as a potential target for diagnostic and therapeutic purposes. Bacteria's ability to metabolically integrate peptidoglycan precursors during cell wall biosynthesis and recycling offers an opportunity to target and image pathogens in their biological state. This Review explores the peptidoglycan biosynthesis for bacteria-specific targeting for infection imaging. Current and potential radiolabeled peptidoglycan precursors for bacterial infection imaging, their development status, and their performance in vitro and/or in vivo are highlighted. We conclude by providing our thoughts on how to shape this area of research for future clinical translation.

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Section: Emerging Radiotracers Targeting Peptidoglycan Biosynthesismentioning

confidence: 99%

Section: Emerging Radiotracers Targeting Peptidoglycan Biosynthesismentioning

confidence: 99%

Section: Park's Nucleotide and Lipid-basedmentioning

confidence: 99%

Section: Park's Nucleotide and Lipid-basedmentioning

confidence: 99%

Section: Design Approach and Challenges For Translationmentioning

confidence: 99%

See 3 more Smart Citations

Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives

Koatale,

Welling,

Ndlovu

et al. 2024

ACS Infect. Dis.

Self Cite

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Imaging the immune sequelae of infection with SARS‐CoV‐2 in nonhuman primates by using two nanobody PET‐tracers

Koopman,

Verhoeven,

Mooij

et al. 2024

Journal of Medical Virology

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Infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) impacts multiple anatomical sites. Whether this is due to the virus itself or is a secondary effect caused by the influx and activation of immune cells is not known. Positron emission tomography (PET) with immunoglobulins can provide insights into which sites and cells are activated in a living animal. Our aim is to use two nanobodies as tools to monitor (1) the distribution of antigen presenting cells (APC) by virtue of their Mafa‐DR expression profile, (2) virus‐infected cells and viral particles using a nanobody against the SARS‐CoV‐2 spike protein. Two [89Zr]‐labeled nanobodies that target the SARS‐CoV‐2 spike protein and major histocompatability complex (MHC) class II antigens (Mafa‐DR), respectively, are used to monitor their distribution during an experimental SARS‐CoV‐2 infection in a nonhuman primate model. Scans are obtained before infection and on Day 3 and 10 post infection (pi) in two macaques each. The [89Zr]anti‐SARS‐CoV‐2 spike nanobody localized to SARS‐CoV‐2‐associated lung lesions and the nasal mucosa, while the [89Zr]anti‐human leukocyte antigen (HLA)‐DR nanobody was predominantly found in non‐affected lung tissue after infection. We also detected, pi, upregulation of the Mafa‐DR signal, indicative of recruitment of professional APCs, in the superior sagittal sinus. [89Zr]‐labeled nanobodies show recruitment of macrophages/monocytes in non‐lesional lung tissue in cynomolgus macaques after experimental infection with SARS‐CoV‐2, as well as accumulation of the spike protein in both lung lesions and the nasal mucosa during infection. These results show the possibility of in vivo monitoring the quality and quantity of immune responses during the initial stages of an infection.

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Amidoxime-based radio-microspheres for Internal Irradiation combined with a checkpoint-blocking nanobody boost antitumor immunity

Zhao,

Chen,

Liu

et al. 2024

Nano Today

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Preclinical Research Highlighting Contemporary Targeting Mechanisms of Radiolabelled Compounds for PET Based Infection Imaging

Cited by 12 publications

References 105 publications

Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives

Insights into Peptidoglycan-Targeting Radiotracers for Imaging Bacterial Infections: Updates, Challenges, and Future Perspectives

Imaging the immune sequelae of infection with SARS‐CoV‐2 in nonhuman primates by using two nanobody PET‐tracers

Amidoxime-based radio-microspheres for Internal Irradiation combined with a checkpoint-blocking nanobody boost antitumor immunity

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