Radiolabeled Cationic Peptides for Targeted Imaging of Infection
Joint Authors
Aweda, Tolulope A.
Muftuler, Zumrut F. B.
Massicano, Adriana V. F.
Gadhia, Dhruval
McCarthy, Kelly A.
Queern, Stacy
Bandyopadhyay, Anupam
Gao, Jianmin
Lapi, Suzanne E.
Source
Contrast Media & Molecular Imaging
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-10-29
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Molecular probes targeting bacteria provide opportunities to target bacterial infections in vivo for both imaging and therapy.
In the current study, we report the development of positron emission tomography (PET) probes for imaging of live bacterial infection based on the small molecules HLys-DOTA, a polycationic peptide synthesized as the D-isomer (RYWVAWRNRG) conjugated to 1, 4, 7, 10-tetraazacyclododecane-N′,N″,N‴,N-tetraacetic acid (DOTA) and AB1-HLys-DOTA, which includes an unnatural amino acid AB1 that preferentially binds to bacteria membrane lipids with amine groups via formation of iminoboronates.
HLys-DOTA and AB1-HLys-DOTA peptides were radiolabeled with 64Cu and investigated as PET imaging agents to track bacterial infection in vitro and in intramuscularly infected (IM) mice models.
Cell uptake studies at 37°C in Staphylococcus aureus (SA) show higher uptake of 64Cu-AB1-HLys-DOTA; 98.47 ± 3.54% vs 64Cu-HLys-DOTA; 39.12 ± 3.27% at 24 h.
Standard uptake values (SUV) analysis of the PET images resulted in mean SUV of 0.70 ± 0.08, 0.49 ± 0.04, and 0.31 ± 0.01 for 64Cu-AB1-HLys-DOTA and 0.17 ± 0.06, 0.16 ± 0.02, and 0.13 ± 0.01 for 64Cu-HLys-DOTA at 1, 4, and 24 h post injection, respectively, in the infected muscles.
Similarly, in the biodistribution studies, dose uptake in the infected muscles was 4 times higher in the targeted 64Cu-AB1-HLys-DOTA group than in the 64Cu-HLys-DOTA group and 2‐3 times higher than in the PBS control group at 1, 4, and 24 h post injection.
64Cu-AB1-HLys-DOTA was able to distinguish between SA-infected muscle and Pseudomonas aeruginosa (PA) infected muscle with lower mean SUV of 0.28 ± 0.10 at 1 h post injection.
This illustrates the utility of the AB1 covalently targeting group in synergy with the HLys peptide, which noncovalently binds to bacterial membranes.
These results suggest that 64Cu-labeled AB1-HLys-DOTA peptide could be used as an imaging probe for detection of bacterial infection in vivo with specificity for Gram-positive bacteria.
American Psychological Association (APA)
Aweda, Tolulope A.& Muftuler, Zumrut F. B.& Massicano, Adriana V. F.& Gadhia, Dhruval& McCarthy, Kelly A.& Queern, Stacy…[et al.]. 2019. Radiolabeled Cationic Peptides for Targeted Imaging of Infection. Contrast Media & Molecular Imaging،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1130213
Modern Language Association (MLA)
Aweda, Tolulope A.…[et al.]. Radiolabeled Cationic Peptides for Targeted Imaging of Infection. Contrast Media & Molecular Imaging No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1130213
American Medical Association (AMA)
Aweda, Tolulope A.& Muftuler, Zumrut F. B.& Massicano, Adriana V. F.& Gadhia, Dhruval& McCarthy, Kelly A.& Queern, Stacy…[et al.]. Radiolabeled Cationic Peptides for Targeted Imaging of Infection. Contrast Media & Molecular Imaging. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1130213
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1130213