Aims: The purpose of this study was to determine the feasibility of a new positron emission tomography (PET) imaging approach using an (18)F-labelled alpha(v)beta(3) integrin antagonist ((18)F-Galacto-RGD) to monitor the integrin expression after myocardial infarction.
Methods And Results: Male Wister rats were subjected to 20 min transient left coronary artery occlusion followed by reperfusion. Autoradiographic analysis and in vivo PET imaging were used to determine myocardial (18)F-Galacto-RGD uptake at different time points following reperfusion.
Results: PET imaging and autoradiography demonstrated no significant focal myocardial (18)F-Galacto-RGD uptake in non-operated control rats and at day 1 after reperfusion. However, focal accumulation in the infarct area started at day 3 (uptake ratio = 1.91 +/- 0.22 vs. remote myocardium), peaked between 1 (3.43 +/- 0.57) and 3 weeks (3.43 +/- 0.95), and decreased to 1.96 +/- 0.40 at 6 months after reperfusion. Pretreatment with alpha(v)beta(3) integrin antagonist c(-RGDfV-) significantly decreased tracer uptake, indicating the specificity of tracer uptake. The time course of focal tracer uptake paralleled vascular density as measured by CD31 immunohistochemical analysis.
Conclusion: Regional (18)F-Galacto-RGD accumulation suggests up-regulation of alpha(v)beta(3) integrin expression after myocardial infarction, which peaks between 1 and 3 weeks and remains detectable until 6 months after reperfusion. This new PET tracer is promising for the monitoring of myocardial repair processes.
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http://dx.doi.org/10.1093/cvr/cvn033 | DOI Listing |
Bioconjug Chem
January 2025
Department of Chemistry, Organic Chemistry Section, Jadavpur University, Kolkata 700032, India.
Herein, a water-soluble, ultrabright, near-infrared (NIR) fluorescent, mechanically interlocked molecules (MIMs)-peptide bioconjugate is designed with dual targeting capabilities. Cancer cell surface overexpressed αβ integrin targeting two RGDS tetrapeptide residues is tethered at the macrocycle of MIMs-peptide bioconjugate via Cu(I)-catalyzed click chemistry on the Wang resin, and mitochondria targeting lipophilic cationic TPP functionality is conjugated at the axle dye. Living carcinoma cell selective active targeting, subsequently cell penetration, mitochondrial imaging, including the ultrastructure of cristae, and real-time tracking of malignant mitochondria by MIMs-peptide bioconjugate (RGDS)-Mito-MIMs-TPP are established by stimulated emission depletion (STED) super-resolved fluorescence microscopy.
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Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, Taiwan, R.O.C.
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January 2025
Department of Pharmacy, The First Affiliated Hospital of University of Science and Technology of China (USTC), Laboratory of Precision and Intelligent Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, Anhui Province, China.
Thiol-maleimide (MI) chemistry is a cornerstone of bioconjugation strategies, particularly in the development of drug delivery systems. The cyclic arginine-glycine-aspartic acid (cRGD) peptide, recognized for its ability to target the integrin αβ, is commonly employed to functionalize maleimide-bearing nanoparticles (NPs) for fabricating cRGD-functionalized nanomedicines. However, the impact of cRGD density on tumor targeting efficiency remains poorly understood.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
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University of California, San Diego, Chemistry and Biochemistry, 9500 Gilman Drive, Urey Hall 4120, 92093, La Jolla, UNITED STATES OF AMERICA.
Membrane-forming phospholipids are generated in cells by enzymatic diacylation of non-amphiphilic polar head groups. Analogous non-enzymatic processes may have been relevant at the origin of life and could have practical utility in membrane synthesis. However, aqueous head group diacylation is challenging in the absence of enzymes.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
Substantial loss of cardiomyocytes during heart attacks and onset of other cardiovascular diseases is a major cause of mortality. Preservation of cardiomyocytes during cardiac injury would be the most effective strategy to manage these diseases in clinic. However, there is no effective treatment strategy that is able to prevent cardiomyocyte loss.
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