Development of 68Ga-labelled DTPA galactosyl human serum albumin for liver function imaging
Development of 68Ga-labelled DTPA galactosyl human serum albumin for liver function imaging
复制标题
DOI：
10.1007/s00259-013-2397-8
复制
发表时间：
2013-08-01
影响因子：
9.1
通讯作者：
Virgolini, Irene J.
中科院分区：
文献类型：
--
作者：
Haubner, Roland;Vera, David R.;Virgolini, Irene J.
肝脏去唾液酸糖蛋白受体负责通过受体介导的内吞作用降解所需的糖蛋白。已有研究表明，用[TC-99m]二乙三胺五乙酸(DTPA)半乳糖人血清白蛋白([TC-99m]GSA)对受体密度进行成像，可以无创地测定功能性肝细胞质量。在这里，我们介绍了[Ga-68]GSA的合成和用于正电子发射断层扫描(PET)的潜在用途的评估。为了进行质量控制，对薄层色谱(TLC)、高效液相色谱(HPLC)和体积排阻色谱(SEC)技术进行了评价。研究了[GA-68]GSA在磷酸盐缓冲液(PBS)和人血清中的稳定性。为了体内评价，采用双同位素方案比较了[Ga-68]GSA在Lewis大鼠体内的分布和[Tc-99m]GSA的分布。使用相同摩尔剂量的[Ga-68]GSA和[TC-99m]GSA进行PET和平面成像研究。绘制了心脏和肝脏的时间-活度曲线(TAC)，并计算了相应的参数(T50，T90)。[Ga-68]GSA的放化纯度较高。用0.1M柠檬酸盐作洗脱液是测定电势游离态Ga-68的最佳TLC方法。所有测试的TLC方法都不能确定潜在的胶体。这可以通过SEC来实现。高效液相色谱法证实放化纯度高(>；98%)。在37摄氏度下孵育120分钟后，PBS(95%完好率示踪剂)的稳定性高，而人血清(接近27%完好率示踪剂)的稳定性低。同时注射两种示踪剂的生物分布研究显示，[Ga-68]GSA的肝脏摄取率与[TC-99m]GSA相当，而[Ga-68]GSA的血中活度浓度高于[Tc-99m]GSA。与[Ga-68]GSA曲线相比，[~(99)m]GSA TAC显示了较小程度的肝脏代谢。[Ga-68]GSA T90平均值高于[Tc-99m]GSA T90平均值。[Ga-68]GSA的平均t50与[TC-99m]GSA的平均t50没有显著差异。这项研究提供了一种有前景的新的Ga-68标记化合物，该化合物基于一种商用试剂盒，用于对功能性肝细胞团块进行成像。
The hepatic asialoglycoprotein receptor is responsible for degradation of desialylated glycoproteins through receptor-mediated endocytosis. It has been shown that imaging of the receptor density using [Tc-99m]diethylenetriamine pentaacetic acid (DTPA) galactosyl human serum albumin ([Tc-99m]GSA) allows non-invasive determination of functional hepatocellular mass. Here we present the synthesis and evaluation of [Ga-68]GSA for the potential use with positron emission tomography (PET).Labelling of GSA with Ga-68 was carried out using a fractionated elution protocol. For quality control thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and size exclusion chromatography (SEC) techniques were evaluated. Stability of [Ga-68]GSA was studied in phosphate-buffered saline (PBS) and human serum. For in vivo evaluation [Ga-68]GSA distribution in Lewis rats was compared with [Tc-99m]GSA by using a dual isotope protocol. PET and planar imaging studies were performed using the same scaled molar dose of [Ga-68]GSA and [Tc-99m]GSA. Time-activity curves (TAC) for heart and liver were generated and corresponding parameters calculated (t50, t90).[Ga-68]GSA can be produced with high radiochemical purity. The best TLC methods for determining potential free Ga-68 include 0.1 M sodium citrate as eluent. None of the TLC methods tested were able to determine potential colloids. This can be achieved by SEC. HPLC confirmed high radiochemical purity (> 98 %). Stability after 120 min incubation at 37 A degrees C was high in PBS (> 95 % intact tracer) and low in human serum (similar to 27 % intact tracer). Biodistribution studies simultaneously injecting both tracers showed comparable liver uptake, whereas activity concentration in blood was higher for [Ga-68]GSA compared to [Tc-99m]GSA. The [Tc-99m]GSA TACs exhibited a small degree of hepatic metabolism compared to the [Ga-68]GSA curves. The mean [Ga-68]GSA t90 was higher than the mean t90 for [Tc-99m]GSA. The mean [Ga-68]GSA t50 was not significantly different from the mean t50 for [Tc-99m]GSA.This study provides a promising new Ga-68-labelled compound based on a commercially used kit for imaging the functional hepatocellular mass.