Key Laboratory of Radiopharmaceuticals, College of Chemistry, Beijing Normal University, Ministry of Education, Beijing 100875, China.
Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China; Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nucl Med Biol. 2020 Mar-Apr;82-83:17-24. doi: 10.1016/j.nucmedbio.2019.12.005. Epub 2019 Dec 16.
[Ga]Ga-EDTA ([Ga]Ga-ethylenediaminetetraacetic acid) was previously reported as a renal imaging agent for measuring GFR (glomerular filtration rate). In an effort to provide new agents with better in vivo characteristics for renal imaging, [Ga]Ga-HBED-CC-DiAsp (Di-Aspartic acid derivative of N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl]-ethylenediamine-N,N'-diacetic acid) was prepared and tested.
HBED-CC-DiAsp was synthesized and labeled with [Ga]GaCl at room temperature. Plasma protein and red blood cells (RBC) binding were also evaluated. Biodistribution and dynamic PET imaging studies were performed in mice and rats, respectively.
[Ga]Ga-HBED-CC-DiAsp was radiolabeled at room temperature by a one-step kit formulation in high purity without any purification (radiochemical purity >98%). Previous reports suggested that Ga-HBED-CC exhibited a higher stability constant and rapid chelating formation rate than that of Ga-EDTA (logK = 38.5 vs 22.1, respectively). In vitro stability studies indicated that it was stable up to 120 min. The log D value, partition coefficient between n-octanol and water, was found to be -2.52 ± 0.08. Plasma protein and RBC binding was similar to that observed for [Ga]Ga-EDTA. Biodistribution and dynamic PET/CT imaging studies in rats revealed a rapid clearance primarily through the renal-urinary pathway. The PET-derived [Ga]Ga-HBED-CC-DiAsp renograms in rats showed an average time-to-peak of 3.6 ± 0.7 min which was similar to that observed for [Ga]Ga-EDTA (3.1 ± 0.5 min). The time-to-half-maximal activity was also comparable to that of [Ga]Ga-EDTA (8.8 vs 8.2 min, respectively). Pretreatment of probenecid, a renal tubular excretion inhibitor, showed no significant effect on renal excretion.
[Ga]Ga-HBED-CC-DiAsp could be prepared quickly at room temperature in high yield and purity. Results of in vitro studies and in vivo biodistribution in mice and rats suggested that [Ga]Ga-HBED-CC-DiAsp might be useful as a PET imaging agent for measurement of GFR.
[Ga]Ga-EDTA（[Ga]Ga-乙二胺四乙酸）以前被报道为一种用于测量肾小球滤过率（GFR）的肾成像剂。为了提供具有更好体内特性的新的肾成像试剂，我们制备并测试了[Ga]Ga-HBED-CC-DiAsp（N，N'-双[2-羟基-5-（羧乙基）苄基]-乙二胺-N，N'-二乙酸的 Di-Aspartic 酸衍生物）。
HBED-CC-DiAsp 是通过室温下的一步试剂盒制剂合成并标记[Ga]GaCl 的。还评估了血浆蛋白和红细胞（RBC）结合。分别在小鼠和大鼠中进行了生物分布和动态 PET 成像研究。
[Ga]Ga-HBED-CC-DiAsp 通过一步试剂盒制剂在室温下以高纯度标记，无需任何纯化（放射化学纯度> 98%）。以前的报告表明，Ga-HBED-CC 的稳定性常数和快速螯合形成速率均高于 Ga-EDTA（分别为 logK = 38.5 和 22.1）。体外稳定性研究表明，它在 120 分钟内稳定。发现其 log D 值（正辛醇与水之间的分配系数）为-2.52 ± 0.08。血浆蛋白和 RBC 结合与观察到的[Ga]Ga-EDTA 相似。大鼠中的生物分布和动态 PET/CT 成像研究表明，其主要通过肾脏-尿液途径快速清除。在大鼠中，PET 衍生的[Ga]Ga-HBED-CC-DiAsp 肾图显示平均达峰时间为 3.6 ± 0.7 分钟，与[Ga]Ga-EDTA（3.1 ± 0.5 分钟）相似。达到最大活性的一半的时间也与[Ga]Ga-EDTA 相当（分别为 8.8 与 8.2 分钟）。肾小管排泄抑制剂丙磺舒预处理对肾排泄无明显影响。
[Ga]Ga-HBED-CC-DiAsp 可以在室温下快速、高产率和高纯度制备。体外研究结果和小鼠及大鼠体内生物分布结果表明，[Ga]Ga-HBED-CC-DiAsp 可用作测量 GFR 的 PET 成像剂。
