Nuclear Medicine and Molecular Imaging

  • 제43권4호
  • /
  • Pages.330-336
  • /
  • 2009
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  • 1869-3474(pISSN)
  • /
  • 1869-3482(eISSN)
대한핵의학회 (The Korean Society of Nuclear Medicine)
권호 표지

양전자 방출핵종 $^{68}$Ga을 이용한 NOTA와 DOTA의 표지 및 시험관내 특성 연구

Radiolabeling of NOTA and DOTA with Positron Emitting $^{68}$Ga and Investigation of In Vitro Properties

  • 정재민 (서울대학교 의과대학 핵의학교실) ;
  • 김영주 (서울대학교 의과대학 핵의학교실) ;
  • 이윤상 (서울대학교 의과대학 핵의학교실) ;
  • 이동수 (서울대학교 의과대학 핵의학교실) ;
  • 정준기 (서울대학교 의과대학 핵의학교실) ;
  • 이명철 (서울대학교 의과대학 핵의학교실)
  • Jeong, Jae-Min (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Kim, Young-Ju (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Lee, Yun-Sang (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Lee, Dong-Soo (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Chung, June-Key (Department of Nuclear Medicine, Seoul National University College of Medicine) ;
  • Lee, Myung-Chul (Department of Nuclear Medicine, Seoul National University College of Medicine)
  • 발행 : 2009.08.30
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초록

목적: $^{68}$Ge/$^{68}$Ga-제너레이터에서 생산되는 PET용 방사성동위원소인 $^{68}$Ga을 NOTA와 DOTA에 표지하는 조건을 확립하고 이의 안정성 및 단백질 결합 특성을 연구하였고, 여러 가지의 금속이온 공존시 표지효율에 미치는 영향도 관찰하였다. 대상 및 방법: 여러 가지 농도의 NOTA 3HCl과 DOTA 4HCl에 $^{68}$Ge/$^{68}$Ga-제너레이터에서 0.1 M HCl로 용출한 $^{68}$GaCl$_3$ 6.66$\sim$272.8 MBq 1.0 mL와 합치고 초산나트륨 또는 탄산나트륨 완충액을 사용하여 다양한 pH 조건에서 반응하였다. 다양한 금속이온(CuCl$_2$, FeCl$_2$, InCl$_3$, FeCl$_3$), GaCl$_3$, MgCl$_2$, CaCl$_2$)과 0.373 mM NOTA를 $^{68}$Ga(6.77$\sim$8.58 MBq)으로 표지할 때 표지효율을 관찰하였다. $^{68}$Ga의 표지효율은 ITLC-SG고정상으로 하고 아세톤과 생리식염수를 이동상으로 하여 측정하였다. 최적의 pH 조건에서 $^{68}$Ga-NOTA와 $^{68}$Ga-DOTA를 표지한 후 4 시간 동안 안정성을 확인하고, 사람 혈청에서의 단백질 결합능을 평가하였으며, 지용성 정도를 측정하기 위하여 octhanol distribulion 실험을 실시하여 log P값을 구하였다. 결과: $^{68}$Ga-NOTA와 $^{68}$Ga-DOTA의 치적 표지 pH 조건은 각각 pH 6.5와 3.5였고, NOTA는 실온에서 표지가 잘 되었으나 DOTA는 가열이 필요하였다. MgCl$_2$와 CaCl$_2$의 존재는 $^{68}$Ga-NOTA의 표지 효율에 영향을 미치지 않았으나 CuCl$_2$, FeCl$_2$, InCl$_3$, FeCl$_3$, GaCl$_3$이 존재할 경우에는 표지효율이 감소하였다. $^{68}$Ga-NOTA와 $^{68}$Ga-DOTA는 실온에 그대로 두거나 사람혈청과 37$^{\circ}C$에 두었을 때 4 시간 이상 안정하였고, 사람 혈청 단백질 결합능은 2.04$\sim$3.32%로 낮았으며, log P 값은 -3.07로 수용성을 보였다. 결론: $^{68}$Ga의 표지에는 NOTA가 DOTA에 비하여 이상적인 양기능성 킬레이트제로 쓰일 수 있음을 알았다. 또한 $^{68}$Ga-NOTA는 금속이온 존재시 표지효율이 떨어질 수 있지만 안정하고 낮은 단백질 결합을 보였다.

Purpose: We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide $^{68}$Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. Materials and Methods: Various concentrations of NOTA 3HCl and DOTA 4HCl were labeled with 1 mL $^{68}$GaCl$_3$ (0.18$\sim$5.75 mCi in 0.1 M HCl in various pH. NOTA 3HCl (0.373 mM) was labeled with $^{68}$GaCl$_3$(0.183$\sim$0.232 mCi/0.1 M HCl 1.0 mL) in the presence of CuCl$_2$, FeCl$_2$, InCl$_3$, FeCl$_3$, GaCl$_3$, MgCl$_2$ or CaCl$_2$ (0$\sim$6.07 mM) at room temperature. The labeling efficiencies of $^{68}$Ga-NOTA and $^{68}$Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. Results: $^{68}$Ga-NOTA and $^{68}$Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37$^{\circ}C$. NOTA was labeled at room temperature while DOTA required heating for labeling. $^{68}$Ga-NOTA labeling efficiency was reduced by CuCl$_2$, FeCl$_2$, InCl$_2$, FeCl$_3$ or CaCl$_3$, however, was not influenced by MgCl$_2$ or CaCl$_2$. The protein binding was low (2.04$\sim$3.32%). Log P value of $^{68}$Ga-NOTA was -3.07 indicating high hydrophilicity. Conclusion: We found that NOTA is a better bifunctional chelating agent than DOTA for $^{68}$Ga labeling. Although, $^{68}$Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.

키워드

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