Ichise Masanori, Cohen Robert M, Carson Richard E
Kreitchman PET Center, Department of Radiology, Columbia University College of Physicians, New York, New York 10032, USA.
J Cereb Blood Flow Metab. 2008 Feb;28(2):420-30. doi: 10.1038/sj.jcbfm.9600530. Epub 2007 Jul 25.
Reference tissue methods to estimate neuroreceptor binding are not applicable to [(18)F]FP-TZTP (a muscarinic-2 cholinergic receptor ligand), because there is no suitable receptor-free reference region. We evaluated a new method to estimate, without using arterial data or a receptor-free reference region, a receptor parameter called the normalized distribution volume, V(T)(), using a region containing receptors as the input tissue. V(T)() is defined as V(T)/K'(1) (distribution volume (V(T)) normalized by K'(1) of the input region). We used a two-parameter multilinear reference tissue model (MRTM2) to generate parametric images of V(T)() and R(1) (R(1)=K(1)/K'(1)) from [(18)F]FP-TZTP PET data of healthy aged subjects (10 with apolipoprotein E-epsilon4 alleles (APOE-epsilon4(+)) and nine without (APOE-epsilon4(-)). V(T)() and V(T) were normalized by plasma-free fraction, f(P). By one-tissue kinetic analysis (1TKA) with metabolite-corrected plasma data, V(T) was previously reported as higher in the APOE-epsilon4(+) group. The noise magnitude of MRTM2 V(T)() and R(1) images were nearly identical to those of 1TKA V(T) and K(1) images. K'(1) or f(P) was not different between the two groups. V(T)() (mins) (1,659+/-497) and V(T) (mL/cm(3)) (701+/-99) in APOE-epsilon4(+) were higher by 38 and 22% than those (1,209+/-233 and 577+/-112) in APOE-epsilon4(-), respectively. The statistical significance for V(T)() (0.041) was lower than that for V(T) (0.025), due to the higher intersubject variability of V(T)() (25%) than that of V(T) (17%). We conclude that MRTM2 V(T)(*) allows detection of group differences in receptor binding without arterial blood or a receptor-free reference region.
用于估计神经受体结合的参考组织方法不适用于[(18)F]FP-TZTP（一种毒蕈碱-2胆碱能受体配体），因为不存在合适的无受体参考区域。我们评估了一种新方法，该方法无需使用动脉数据或无受体参考区域，而是使用包含受体的区域作为输入组织来估计一种称为归一化分布容积V(T)()的受体参数。V(T)()定义为V(T)/K'(1)（分布容积V(T)通过输入区域的K'(1)进行归一化）。我们使用双参数多线性参考组织模型（MRTM2）从健康老年受试者（10名携带载脂蛋白E-ε4等位基因（APOE-ε4(+)）和9名不携带（APOE-ε4(-)））的[(18)F]FP-TZTP PET数据生成V(T)()和R(1)（R(1)=K(1)/K'(1)）的参数图像。V(T)()和V(T)通过无血浆分数f(P)进行归一化。通过对代谢物校正后的血浆数据进行单组织动力学分析（1TKA），先前报道APOE-ε4(+)组的V(T)较高。MRTM2的V(T)()和R(1)图像噪声幅度与1TKA的V(T)和K(1)图像几乎相同。两组之间的K'(1)或f(P)没有差异。APOE-ε4(+)组的V(T)()（分钟）（1,659±497）和V(T)（mL/cm³）（701±99）分别比APOE-ε4(-)组（1,209±233和577±112）高38%和22%。由于V(T)()（25%）的受试者间变异性高于V(T)（17%），V(T)()的统计学显著性（0.041）低于V(T)（0.025）。我们得出结论，MRTM2的V(T)(*)无需动脉血或无受体参考区域即可检测受体结合的组间差异。
