Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran; Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
Bioorg Chem. 2020 Mar;96:103572. doi: 10.1016/j.bioorg.2020.103572. Epub 2020 Jan 8.
In this research, early diagnosis of cardiovascular diseases can reduce their mortality and burden. In our study, we developed a new nano-agent, Tc-Dendrimer Glyco Conjugate (Tc-DGC), and assessed its safety and capability for myocardial viability scan. To develop Tc-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 Tc-DGC in rats with no infarction. DGC synthesis was confirmed by Fourier transform infrared (FT-IR), proton nuclear magnetic resonance (H 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 Tc. 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 Tc-DGC in myocardial. Biodistribution result showed the 2.60% accumulation of Tc-DGC in myocardial after 2 h. Our findings indicated Tc-DGC to be safe and can accurately diagnose myocardial infarctions at early stages. Human studies to further assess such effects are critical.
在这项研究中，心血管疾病的早期诊断可以降低其死亡率和负担。在我们的研究中，我们开发了一种新的纳米制剂 Tc-树枝状大分子糖缀合物（Tc-DGC），并评估了它用于心肌存活扫描的安全性和能力。为了开发 Tc-DGC，我们首先合成了树枝状大分子，然后将葡萄糖与之缀合。之后，我们通过 XTT 和细胞凋亡/坏死方法测量了产品对正常细胞的毒性。我们比较了两种兔模型（有和没有梗塞）的心肌存活扫描（通过 SPECT 和动态平面成像测量）。我们还评估了没有梗塞的大鼠中 Tc-DGC 的生物分布。DGC 合成通过傅里叶变换红外（FT-IR）、质子核磁共振（H NMR）、液相色谱-质谱（LC-MS）、动态光散射（DLS）和静态光散射技术（SLS）得到证实。然后进行放射性化学纯度（RCP）以显示 DGC 与 Tc 形成络合物的稳定性和潜力。体外细胞毒性表明，非毒性浓度高达 8mg/mL。单光子发射计算机断层扫描（SPECT）和动态平面成像清楚地显示了 Tc-DGC 在心肌中的积累。生物分布结果表明，Tc-DGC 在 2 小时后在心肌中的积累率为 2.60%。我们的研究结果表明 Tc-DGC 是安全的，可以准确诊断早期心肌梗塞。对进一步评估这些效果的人体研究至关重要。
