Synthesis and characterization of novel 99mTc-DGC nano-complexes for improvement of heart diagnostic

Bioorg Chem. 2020 Mar:96:103572. doi: 10.1016/j.bioorg.2020.103572. Epub 2020 Jan 8.

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.

Keywords: Biocompatible; Biodegradable; Chelator free; Dendrimer; Glucosamine; Radiolabeling.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Chromatography, Liquid / methods*
  • Dendrimers / chemistry*
  • Disease Models, Animal
  • Glycoconjugates / chemistry*
  • HEK293 Cells
  • Heart Diseases / diagnostic imaging*
  • Humans
  • Mass Spectrometry / methods*
  • Organotechnetium Compounds / chemistry*
  • Organotechnetium Compounds / pharmacokinetics
  • Organotechnetium Compounds / pharmacology
  • Proton Magnetic Resonance Spectroscopy / methods*
  • Rabbits
  • Spectroscopy, Fourier Transform Infrared / methods*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Dendrimers
  • Glycoconjugates
  • Organotechnetium Compounds