24 research outputs found
Radiolabeled Cationic Peptides for Targeted Imaging of Infection
No full textMolecular 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. © 2019 Tolulope A. Aweda et al.National Institute of General Medical Sciences, NIGMS: R01GM10273
Combination of isothermal titration calorimetry and time-resolved luminescence for high affinity antibody–ligand interaction thermodynamics and kinetics
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A novel anti-angiogenic radio/photo sensitizer for prostate cancer imaging and therapy: Zr-89-Pt@TiO2-SPHINX, synthesis and in vitro evaluation
No full textProstate cancer is the most common malignancy and leading cause of cancer deaths in men. Thus, the development of novel strategies for performing combined prostate cancer imaging and therapy methods is crucial and could have a significant impact on patient care. This current study aimed to design a multimodality nanoconjugate to be used for both PET and optical imaging and as a therapeutic radio/photo sensitizer and anti-angiogenesis agent. Initial characterization of this novel nanoconjugate was performed via HPLC, FTIR, TEM and DLS analyses. Pt@TiO2-SPHINX was further evaluated using fluorometric and radiochromatographicmethods. Cytotoxicity, cell uptake and internalizationwere also investigated as well as therapy with photodynamic/radio therapy combinations. Both nanoparticles and nanoconjugates were robustly synthesized according to literature methods. Radiochemistry and cell culture assays showed high Zr-89 radiolabeling efficiency with sufficient stability for studies at later time points. Pt@TiO2-SPHINX was shown to target prostate cancer cells (PC3 and LNCaP), and was non-toxic to normal prostate cells (RWPE-1). This finding was supported by the WST-8 assay and AFM images. The uptake of the compound in prostate cancer cells is significantly higher than prostate normal cells and according to ELISA results, Pt@TiO2-SPHINX can increase anti-angiogenic VEGFA(165b). Additionally, Pt@TiO2-SPHINX dramatically decreased the cell viability of prostate cancer cells when photodynamic and radio therapy were performed at the same time. in vitro results are promising for future studies of Pt@TiO2-SPHINX as a PET imaging agent and anti-angiogenic radio sensitizer. (C) 2021 Elsevier Inc. All rights reserved.Scientific and Technological Research Council of Turkey (TUBITAK) Science FellowshipsTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); University of Alabama at Birmingham (UAB), Alabama, USA [2214]; Ege University Research FundEge University [2016NBE006]; UAB Department of RadiologyThe author, Dr. Volkan Tekin, was financially supported by The Scientific and Technological Research Council of Turkey (TUBITAK) Science Fellowships and Grant Programme Directorate, during which he performed some experiments of this study at the University of Alabama at Birmingham (UAB), Alabama, USA, with an International Graduate Research Fellowship Program-2214. This project was also financially supported by Ege University Research Fund (contract no. 2016NBE006) and the UAB Department of Radiology
Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52
No full textManganese is essential to life, and humans typically absorb sufficient quantities of this element from a normal healthy diet; however, chronic, elevated ingestion or inhalation of manganese can be neurotoxic, potentially leading to manganism. Although imaging of large amounts of accumulated Mn(II) is possible by MRI, quantitative measurement of the biodistribution of manganese, particularly at the trace level, can be challenging. In this study, we produced the positron-emitting radionuclide 52Mn (t1/2 = 5.6 d) by proton bombardment (Ep<15 MeV) of chromium metal, followed by solid-phase isolation by cation-exchange chromatography. An aqueous solution of [52Mn]MnCl2 was nebulized into a closed chamber with openings through which mice inhaled the aerosol, and a separate cohort of mice received intravenous (IV) injections of [52Mn]MnCl2. Ex vivo biodistribution was performed at 1 h and 1 d post-injection/inhalation (p.i.). In both trials, we observed uptake in lungs and thyroid at 1 d p.i. Manganese is known to cross the blood-brain barrier, as confirmed in our studies following IV injection (0.86%ID/g, 1 d p.i.) and following inhalation of aerosol, (0.31%ID/g, 1 d p.i.). Uptake in salivary gland and pancreas were observed at 1 d p.i. (0.5 and 0.8%ID/g), but to a much greater degree from IV injection (6.8 and 10%ID/g). In a separate study, mice received IV injection of an imaging dose of [52Mn]MnCl2, followed by in vivo imaging by positron emission tomography (PET) and ex vivo biodistribution. The results from this study supported many of the results from the biodistribution-only studies. In this work, we have confirmed results in the literature and contributed new results for the biodistribution of inhaled radiomanganese for several organs. Our results could serve as supporting information for environmental and occupational regulations, for designing PET studies utilizing 52Mn, and/or for predicting the biodistribution of manganese-based MR contrast agents
Radiosynthesis and Biological Distribution of <sup>18</sup>F-Labeled Perfluorinated Alkyl Substances
No full textComparative Uptake and Biological Distribution of [18F]-Labeled C6 and C8 Perfluorinated Alkyl Substances in Pregnant Mice via Different Routes of Administration
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