Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage,Journal of Medicinal Chemistry

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Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2017-06-27 00:00:00 , DOI: 10.1021/acs.jmedchem.7b00234
Rachel C. Stewart _{1,

2} , Amit N. Patwa ₁ , Hrvoje Lusic ₁ , Jonathan D. Freedman _{1,

2} , Michel Wathier ₃ , Brian D. Snyder ₂ , Ali Guermazi ₄ , Mark W. Grinstaff ₁

Affiliation

Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

中文翻译：

阳离子碘化造影剂（CA4 +）的合成，临床前表征及其在离体人体髋关节软骨定量计算机断层扫描中的应用

超越定性可视化并能够对功能组织性能进行定量评估的造影剂代表了下一代临床有用的成像工具。阳离子碘化造影剂（CA4 +）的优化和高效大规模合成用于成像关节软骨。与相似的阴离子或非离子药物相比，使用CA4 +的增强CT（CECT）显示关节软骨中CA4 +的药物吸收明显更高，并且CA4 +的吸收遵循Donnan平衡理论。通过对离体人体髋关节软骨进行成像获得的CA4 + CECT衰减与糖胺聚糖含量，平衡模量和摩擦系数相关，这是软骨功能性能和骨关节炎阶段的关键指标。最后，

更新日期：2017-06-28

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