Investigative Magnetic Resonance Imaging

Korean Society of Magnetic Resonance in Medicine (대한자기공명의과학회)
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Pharmacokinetics and Bio-distribution of New Gd-complexes of DTPA-bis (amide) (L3) in a Rat Model

쥐를 이용한 새로운 가돌리늄 조영제 Gd-DTPA-bis(amide)(L3)의 약동학 및 생체내 분포 특성에 대한 연구

  • Yan, Gen (Department of Radiology, the Second Affiliated Hospital, Shantou University Medical College) ;
  • Wu, Renhua (Department of Radiology, the Second Affiliated Hospital, Shantou University Medical College) ;
  • Chang, Yongmin (Department of Radiology & Molecular Medicine, Kyungpook National University) ;
  • Kang, Duksik (Department of Radiology, Bogang Hospital)
  • ;
  • ;
  • 장용민 (경북대학교 의과대학 분자의학교실 및 경북대학교병원 영상의학과) ;
  • 강덕식 (대구 보강병원 영상의학과)
  • Received : 2013.10.30
  • Accepted : 2013.12.13
  • Published : 2013.12.27
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Abstract

Purpose : To investigate the blood pharmacokinetics and bio-distribution of DTPA-bis-amide (L3) Gd(III) complexes. Materials and Methods: The pharmacokinetics and bio-distribution of Gd $(L3)(H_2O){\cdot}nH_2O$ were investigated in Sprague-Dawley rats after intravenous administration at a dose of 0.1 mmol Gd/kg. The Gd content in the blood, various tissues, and organs was determined by ICP-AES. Blood pharmacokinetic parameters were calculated using a two-compartment model. Results: The half-lives of ${\alpha}$ phase and ${\beta}$ phase Gd $(L3)(H_2O){\cdot}nH_2O$ were $2.286{\pm}0.11$ min and $146.1{\pm}7.5$ min, respectively. The bio-distribution properties reveal that the complex is mainly excreted by the renal pathway, and possibly excreted by the hepatobiliary route. The concentration ratio of Gd (III) was significantly higher in the liver and spleen than in other organs, and small amounts of Gd (III) ion were detected in the blood or other tissues of rats only after 7 days of intravenous administration. Conclusion: The MRI contrast agent Gd $(L3)(H_2O){\cdot}nH_2O$ provides prolonged blood pool retention in the circulation and then clears rapidly with minimal accumulation of Gd(III) ions. The synthesis of gadolinium complexes with well-balanced lipophilicity and hydrophilicity shows promise for their further development as blood pool MRI contrast agents.

목적: DTPA-bis-amide (L3) Gd(III) 복합체의 약동학 및 생체내 분포특성을 조사하고자 하였다. 대상과 방법: Sprague-Dawley 쥐의 꼬리정맥을 통하여 0.1 mmol Gd/kg의 DTPA-bis-amide (L3) Gd(III) 복합체를 주사한 후 약동학 및 생체내 분포 특성을 조사하였다. 조직 및 장기 그리고 혈중 Gd 농도를 ICP-AES를 사용하여 정량 측정하였으며 혈중 약동학적 파라미터는 two-compartment 모델을 사용하여 계산하였다. 결과: DTPA-bis-amide (L3) Gd(III) 복합체의 혈중 반감기는 ${\alpha}$-phase의 경우 $2.286{\pm}0.11$ min 그리고 ${\beta}$-phase의 경우 $146.1{\pm}7.5$ min 이었다. 생체내 분포특성은 주요 배설 경로는 신장을 통한 배설이 주요 경로였으며 일부 담도계를 통한 배설이 확인되었다. 또한 Gd(III)의 농도비는 다른 장기에 비해 간과 비장에서 매우 높은 농도를 보였으며 일부 Gd(III)이 정맥주사 후 7일후에 혈액 및 일부 장기에서 매우 소량 검출되었다. 결론: 새로운 조영제인 DTPA-bis-amide (L3) Gd(III) 복합체는 혈중 잔류시간이 상대적으로 길면서도 체내 축적없이 체외로 배출되는 특성을 나타내었다. 따라서 친지질성과 친수성의 균형이 잘 이루어진 가돌리늄 조영제의 합성은 향후 blood pool MRI 조영제로써의 가능성이 매우 높은 것으로 판단된다.

Keywords

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