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Synthesis of a gadolinium based-macrocyclic MRI contrast agent for effective cancer diagnosis

  • Jeong, Yohan (Department of Biotechnology, The Catholic University of Korea) ;
  • Na, Kun (Department of Biotechnology, The Catholic University of Korea)
  • 투고 : 2018.03.29
  • 심사 : 2018.06.01
  • 발행 : 2018.06.01

초록

Background: Gadolinium-based contrast agents are widely used as a contrast agent for magnetic resonance imaging. Since gadolinium ions are toxic, many chelators are developed to bind gadolinium ions to prevent free gadolinium-associated disease. However, many reports indicated that linear chelator-based contrast agents are associated with nephrogenic systemic fibrosis (NSF) in patients with low kidney function. Therefore, the demand for stable macrocyclic chelator-based contrast agent is now increasing. Method: 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) was conjugated to lactobionic acid (LBA) through DCC-NHS coupling reaction. $Gd^{3+}$ (gadolinium ion) was chelated to 1,4,7,10-Tetraazacyclododecane1,4,7,10-tetraacetate-lactobionic acid (DOTA-LAE) and free $Gd^{3+}$ was removed using a cation exchange column. In vitro cytotoxicity of contrast agent towards normal cells was measured using MTT assay. For in vivo MR imaging, contrast agents were intravenously injected to tumor-bearing mice and imaged by a MR imaging scanner. Results: This new macrocyclic gadolinium-based contrast agent showed enhanced in vitro paramagnetic properties compared to Gadovist. In addition, Gd-DOTA-LAE showed a 29% increased contrast enhancement of tumor tissue compared to normal tissue within 20 min past IV injection. Conclusions: We developed a new macrocyclic T1-weighted MR contrast agent. This new contrast agent offers various opportunities for cancer detection and diagnosis.

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