源自N,N'-双(3-氨丙基)-N,N'-二甲基乙二胺的亲脂性单阳离子镓放射性药物的合成与生物分布：用68Ga进行PET心肌成像的潜在药物。
Synthesis and biodistribution of lipophilic and monocationic gallium radiopharmaceuticals derived from N,N'-bis(3-aminopropyl)-N,N'-dimethylethylenediamine: potential agents for PET myocardial imaging with 68Ga.
作者信息
Hsiao Yui-May, Mathias Carla J, Wey Shiaw-Pyng, Fanwick Phillip E, Green Mark A
机构信息
Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
出版信息
Nucl Med Biol. 2009 Jan;36(1):39-45. doi: 10.1016/j.nucmedbio.2008.10.010.
INTRODUCTION
In locations that lack nearby cyclotron facilities for radionuclide production, generator-based (68)Ga radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiological processes.
METHODS
The lipophilic and monocationic (67)Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-meth,oxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N'-bis(3-aminopropyl)-N,N'-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled Ga(4-MeOsal)(2)BAPDMENPF(6)(-) salt was determined by X-ray crystallography, and the biodistribution of each of the (67)Ga-labeled gallium chelates was determined in rats following intravenous administration and compared with the biodistribution of [(86)Rb]rubidium chloride.
RESULTS
The Ga(4-MeOsal)(2)BAPDMENPF(6)(-) complex exhibited the expected pseudo-octahedral N(4)O(2)(2-) coordination sphere about the Ga(3+) center with a trans disposition of the phenolate oxygen atoms. All five (67)Ga radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [(67/68)Ga]Ga(3-MeOsal)(2)BAPDMEN radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart 1 min and 2 h postinjection and very high heart/nontarget ratios (heart/blood ratios of 7.6+/-1.0 and 54+/-10 at 1 and 120 min, respectively; heart/liver ratios of 1.8+/-0.4 and 39+/-3 at 1 and 120 min, respectively).
CONCLUSIONS
Most of these new agents, particularly [(67/68)Ga]Ga(3-MeOsal)(2)BAPDMEN, would appear superior to previously reported bis(salicylaldimine) ligands of N,N'-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with (68)Ga.
引言
在缺乏用于放射性核素生产的附近回旋加速器设施的地区，基于发生器的（68）Ga放射性药物可能对心肌灌注和其他生理过程的正电子发射断层扫描（PET）研究具有临床应用价值。
方法
制备了五种新型六齿双（水杨醛亚胺）配体N，N'-双（3-氨丙基）-N，N'-二甲基乙二胺（BAPDMEN）的亲脂性单阳离子（67）Ga标记的镓螯合物，即双（水杨醛亚胺）、双（3-甲氧基水杨醛亚胺）、双（4-甲氧基水杨醛亚胺）、双（6-甲氧基水杨醛亚胺）和双（4,6-二甲氧基水杨醛亚胺）。通过X射线晶体学确定了未标记的Ga(4-MeOsal)(2)BAPDMENPF(6)(-)盐的结构，并在静脉注射后在大鼠中测定了每种（67）Ga标记的镓螯合物的生物分布，并与[（86）Rb]氯化铷的生物分布进行了比较。
结果
Ga(4-MeOsal)(2)BAPDMENPF(6)(-)配合物在Ga(3+)中心周围表现出预期的伪八面体N(4)O(2)(2-)配位球，酚盐氧原子呈反式排列。发现所有五种（67）Ga放射性药物都能使放射性镓在心肌中保持所需的水平。[（67/68）Ga]Ga(3-MeOsal)(2)BAPDMEN放射性药物似乎具有最佳的心肌成像特性，在注射后1分钟和2小时心脏中分别占注射剂量的2%，并且心脏/非靶器官比值非常高（1分钟和120分钟时心脏/血液比值分别为7.6±1.0和54±10；1分钟和120分钟时心脏/肝脏比值分别为1.8±0.4和39±3）。
结论
这些新试剂中的大多数，特别是[（67/68）Ga]Ga(3-MeOsal)(2)BAPDMEN，作为用（68）Ga进行心脏PET成像的候选物，似乎优于先前报道的N，N'-双（3-氨丙基）乙二胺的双（水杨醛亚胺）配体。
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