Title of article :
Radiolabeled Cationic Peptides for Targeted Imaging of Infection
Author/Authors :
Aweda, Tolulope A Department of Radiology - University of Alabama at Birmingham - Birmingham, USA , Muftuler, Zumrut F. B University of Ege at Izmir - Izmir, Turkey , Massicano, Adriana V. F Department of Radiology - University of Alabama at Birmingham - Birmingham, USA , Gadhia, Dhruval Department of Radiology - University of Alabama at Birmingham - Birmingham, USA , McCarthy, Kelly A Department of Chemistry - Boston College - Chestnut Hill - Newton, USA , Queern, Stacy Department of Radiology - University of Alabama at Birmingham - Birmingham, USA , Bandyopadhyay, Anupam Department of Chemistry - Indian Institute of Technology - Ropar - Punjab, India , Gao, Jianmin Department of Chemistry - Boston College - Chestnut Hill - Newton, USA , Lapi, Suzanne E Department of Radiology - University of Alabama at Birmingham - Birmingham, USA
Abstract :
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. is illustrates the utility of the AB1 covalently
targeting group in synergy with the HLys peptide, which noncovalently binds to bacterial membranes. ese results suggest that
64Cu-labeled AB1-HLys-DOTA peptide could be used as an imaging probe for detection of bacterial infection in vivo with
speci¢city for Gram-positive bacteria.
Keywords :
Radiolabeled , PET/CT , PBS
Journal title :
Contrast Media and Molecular Imaging
