使用[(18)F]PSS232以最小侵入性和降低模型复杂性对大鼠脑内代谢型谷氨酸受体5进行定量正电子发射断层扫描。
Quantitative positron emission tomography of mGluR5 in rat brain with [(18) F]PSS232 at minimal invasiveness and reduced model complexity.
作者信息
Müller Herde Adrienne, Keller Claudia, Milicevic Sephton Selena, Mu Linjing, Schibli Roger, Ametamey Simon M, Krämer Stefanie D
机构信息
Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences (D-CHAB), ETH Zurich, Zurich, Switzerland.
出版信息
J Neurochem. 2015 May;133(3):330-42. doi: 10.1111/jnc.13001. Epub 2015 Jan 28.
Imaging the density of metabotropic glutamate receptor 5 (mGluR5) in brain by positron emission tomography (PET) is of interest in relation to several brain disorders. We have recently introduced [(18) F]PSS232, an F-18-labeled analog of the mGluR5-targeting [(11) C]ABP688. Quantitative PET requires kinetic modeling with an input function (IF) or an appropriate reference tissue model. We aimed at minimizing invasiveness of IF recording in rat and employing this protocol for mGluR5 quantitative PET with [(18) F]PSS232. We further aimed at defining models of low complexity for quantitative PET with [(18) F]PSS232. The IF was recorded in an arterio-venous shunt applied by minimally invasive cannulation. PET data were analyzed with a modified two-tissue compartment model including a single variable for radiometabolite correction in brain. We further evaluated a simple reference tissue model. Receptor-dependent accumulation was similar to [(11) C]ABP688 at lower unspecific accumulation of unchanged [(18) F]PSS232, in agreement with its higher plasma protein binding and lower lipophilicity. The minimally invasive protocol revealed similar results as the invasive shunt method and parameters calculated with the modified two-tissue compartment model were similar to those calculated with the standard model. The simple area under the curve ratios agreed with the Logan reference method. [(18) F]PSS232 is a promising radioligand for mGluR5 quantification. Methods were evaluated to quantify mGluR5 in rat brain by PET with [(18) F]PSS232. We present a minimally invasive protocol for input function recording. A two-tissue compartment model correcting for radiometabolites at reduced complexity is compared with the standard model. Finally, we demonstrate and explain why for [(18) F]PSS232 the area-under-the-curve ratio is a valid alternative to the Logan reference tissue analysis.
通过正电子发射断层扫描(PET)对大脑中代谢型谷氨酸受体5(mGluR5)的密度进行成像,与多种脑部疾病相关,备受关注。我们最近引入了[(18)F]PSS232,它是靶向mGluR5的[(11)C]ABP688的F-18标记类似物。定量PET需要使用输入函数(IF)或适当的参考组织模型进行动力学建模。我们旨在将大鼠IF记录的侵入性降至最低,并将此方案用于[(18)F]PSS232的mGluR5定量PET。我们还旨在为[(18)F]PSS232的定量PET定义低复杂度模型。IF通过微创插管应用的动静脉分流进行记录。PET数据采用改良的双组织隔室模型进行分析,该模型包括一个用于脑内放射性代谢物校正的单一变量。我们还评估了一个简单的参考组织模型。在未改变的[(18)F]PSS232非特异性积累较低时,受体依赖性积累与[(11)C]ABP688相似,这与其较高的血浆蛋白结合率和较低的亲脂性一致。微创方案显示的结果与侵入性分流方法相似,用改良双组织隔室模型计算的参数与用标准模型计算的参数相似。简单的曲线下面积比值与洛根参考方法一致。[(18)F]PSS232是用于mGluR5定量的有前景的放射性配体。对使用[(18)F]PSS232通过PET定量大鼠脑内mGluR5的方法进行了评估。我们提出了一种用于输入函数记录的微创方案。将一种在降低复杂度的情况下校正放射性代谢物的双组织隔室模型与标准模型进行了比较。最后,我们证明并解释了为什么对于[(18)F]PSS232,曲线下面积比值是洛根参考组织分析的有效替代方法。