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Synthesis and Characterization of Novel 99Mtc-Dgc Nano-Complexes for Improvement of Heart Diagnostic Publisher Pubmed



Ardestani MS1 ; Bitarafanrajabi A2, 3 ; Mohammadzadeh P1, 4 ; Mortazaviderazkola S5 ; Sabzevari O6 ; Azar AD7 ; Kazemi S8 ; Hosseini SR1 ; Ghoreishi SM1, 8
Authors
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Authors Affiliations
  1. 1. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  3. 3. Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Biomedical Sciences, Colorado State University, Fort Collins, 80523, CO, United States
  5. 5. Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran
  6. 6. Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

Source: Bioorganic Chemistry Published:2020


Abstract

In this research, early diagnosis of cardiovascular diseases can reduce their mortality and burden. In our study, we developed a new nano-agent, 99mTc-Dendrimer Glyco Conjugate (99mTc-DGC), and assessed its safety and capability for myocardial viability scan. To develop 99mTc-DGC, we first synthesized the dendrimer and then, glucose has been conjugated. Afterwards, we measured toxicity of the product on normal cells by XTT and apoptosis/necrosis methods. We compared the myocardial viability scan (measured by SPECT and dynamic planar imaging) in two rabbit models, with and without infarction. We also assessed the biodistribution of 99mTc-DGC in rats with no infarction. DGC synthesis was confirmed by Fourier transform infrared (FT-IR), proton nuclear magnetic resonance (1H NMR), liquid chromatography-mass spectrometry (LC-MS), dynamic light scattering (DLS) and static light scattering techniques (SLS). Then radiochemical purity (RCP) was done to present the stability and potential of DGC to complex formation with 99mTc. In vitro cytotoxicity showed nontoxic concentration up to 8 mg/mL. Single Photon Emission Computed Tomography (SPECT) and dynamic planar imaging clearly showed the accumulation of 99mTc-DGC in myocardial. Biodistribution result showed the 2.60% accumulation of 99mTc-DGC in myocardial after 2 h. Our findings indicated 99mTc-DGC to be safe and can accurately diagnose myocardial infarctions at early stages. Human studies to further assess such effects are critical. © 2020 Elsevier Inc.
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