DOI QR코드

DOI QR Code

In vivo Imaging Biodistribution Profile of a New Macrocyclic Gadolinium Chelate as a Highly Stable Multifunctional MRI Contrast Agent

  • Sung, Bo Kyung (Department of Medical & Biological Engineering, Kyungpook National University) ;
  • Jo, Yeong Woo (Hana Pharm Co., Pangyo R&D Center) ;
  • Chang, Yongmin (Department of Medical & Biological Engineering, Kyungpook National University)
  • 투고 : 2018.10.23
  • 심사 : 2018.11.19
  • 발행 : 2019.03.29

초록

Gadolinium contrast agents (CAs) are integral components of clinical magnetic resonance imaging (MRI). However, safety concerns have arisen regarding the use of gadolinium CAs, due to their association with nephrogenic systemic fibrosis (NSF). Furthermore, recently the long-term retention of $Gd^{3+}-based$ CAs in brains patients with normal renal function raised another possible safety issue. The safety concerns of $Gd^{3+}-based$ CAs have been based on the ligand structure of $Gd^{3+}-based$ CAs, and findings that $Gd^{3+}-based$ CAs with linear ligand structures showed much higher incidences of NSF and brain retention of CAs than $Gd^{3+}-based$ CAs with macrocyclic ligand structure. In the current study, we report the in vivo biodistribution profile of a new highly stable multifunctional $Gd^{3+}-based$ CA, with macrocyclic ligand structure (HNP-2006). MR imaging using HNP-2006 demonstrated a significant contrast enhancement in many different organs. Furthermore, the contrast enhanced tumor imaging using HNP-2006 confirmed that this new macrocyclic CA can be used for detecting tumor in the central nervous system. Therefore, this new multifunctional HNP-2006 with macrocyclic ligand structure shows great promise for whole-body clinical application.

키워드

참고문헌

  1. Geraldes CF, Laurent S. Classification and basic properties of contrast agents for magnetic resonance imaging. Contrast Media Mol Imaging 2009;4:1-23 https://doi.org/10.1002/cmmi.265
  2. Grobner T. Gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21:1104-1108 https://doi.org/10.1093/ndt/gfk062
  3. Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17:2359-2362 https://doi.org/10.1681/ASN.2006060601
  4. Kanda T, Fukusato T, Matsuda M, et al. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 2015;276:228-232 https://doi.org/10.1148/radiol.2015142690
  5. Broome DR. Nephrogenic systemic fibrosis associated with gadolinium based contrast agents: a summary of the medical literature reporting. Eur J Radiol 2008;66:230-234 https://doi.org/10.1016/j.ejrad.2008.02.011
  6. Kim HK, Lee GH, Chang Y. Gadolinium as an MRI contrast agent. Future Med Chem 2018;10:639-661 https://doi.org/10.4155/fmc-2017-0215
  7. European Medicines Agency. PRAC concludes assessment of gadolinium agents used in body scans and recommends regulatory actions, including suspension for some marketing authorisations. 2017
  8. Gu S, Kim HK, Lee GH, Kang BS, Chang Y, Kim TJ. Gd-complexes of 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-1,4,7,10-tetraacetic acid (DOTA) conjugates of tranexamates as a new class of blood-pool magnetic resonance imaging contrast agents. J Med Chem 2011;54:143-152 https://doi.org/10.1021/jm100966t
  9. Narita M, Hatano E, Arizono S, et al. Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. J Gastroenterol 2009;44:793-798 https://doi.org/10.1007/s00535-009-0056-4