Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
J Nucl Med. 2013 Jul;54(7):1127-34. doi: 10.2967/jnumed.112.114660. Epub 2013 May 31.
The progression of β-amyloid deposition in the brains of mice overexpressing Swedish mutant β-amyloid precursor protein (APP-Swe), a model of Alzheimer disease (AD), was investigated in a longitudinal PET study using the novel β-amyloid tracer (18)F-florbetaben.
Groups of APP-Swe and age-matched wild-type (WT) mice (age range, 10-20 mo) were investigated. Dynamic emission recordings were acquired with a small-animal PET scanner during 90 min after the administration of (18)F-florbetaben (9 MBq, intravenously). After spatial normalization of individual PET recordings to common coordinates for mouse brain, binding potentials (BPND) and standardized uptake value ratios (SUVRs) were calculated relative to the cerebellum. Voxelwise analyses were performed using statistical parametric mapping (SPM). Histochemical analyses and ex vivo autoradiography were ultimately performed in a subset of animals as a gold standard assessment of β-amyloid plaque load.
SUVRs calculated from static recordings during the interval of 30-60 min after tracer injection correlated highly with estimates of BPND based on the entire dynamic emission recordings. (18)F-florbetaben binding did not significantly differ in APP-Swe mice and WT animals at 10 and 13 mo of age. At 16 mo of age, the APP-Swe mice had a significant 7.9% increase (P < 0.01) in cortical (18)F-florbetaben uptake above baseline and at 20 mo there was a 16.6% increase (P < 0.001), whereas WT mice did not show any temporal changes in tracer uptake during the interval of follow-up. Voxelwise SPM analyses revealed the first signs of increased cortical binding at 13 mo and confirmed progressive binding increases in both the frontal and the temporal cortices (P < 0.001 uncorrected) to 20 mo. The SUVR strongly correlated with percentage plaque load (R = 0.95, P < 0.001).
In the first longitudinal PET study in an AD mouse model using the novel β-amyloid tracer (18)F-florbetaben, the temporal and spatial progression of amyloidogenesis in the brain of APP-Swe mice were sensitively monitored. This method should afford the means for preclinical testing of novel therapeutic approaches to the treatment of AD.
使用新型β-淀粉样蛋白示踪剂（18）F-氟比他滨，在阿尔茨海默病（AD）模型——过表达瑞典突变β-淀粉样前体蛋白（APP-Swe）的小鼠的大脑中，对β-淀粉样蛋白沉积的进展进行纵向 PET 研究。
研究了 APP-Swe 和年龄匹配的野生型（WT）小鼠（年龄范围为 10-20 个月）组。在静脉注射（18）F-氟比他滨（9MBq）后 90 分钟内，使用小动物 PET 扫描仪进行动态发射记录。在将个体 PET 记录空间归一化为小鼠大脑的共同坐标后，相对于小脑计算结合潜力（BPND）和标准化摄取比值（SUVR）。使用统计参数映射（SPM）进行体素分析。最终在一部分动物中进行了组织化学分析和离体放射性自显影，作为β-淀粉样斑块负荷的金标准评估。
在注射示踪剂后 30-60 分钟期间的静态记录中计算出的 SUVR 与基于整个动态发射记录的 BPND 估计值高度相关。在 10 个月和 13 个月龄时，APP-Swe 小鼠和 WT 动物的（18）F-氟比他滨结合没有显著差异。在 16 个月龄时，APP-Swe 小鼠皮质（18）F-氟比他滨摄取量比基线增加了 7.9%（P <0.01），而在 20 个月龄时增加了 16.6%（P <0.001），而 WT 小鼠在整个随访期间没有显示示踪剂摄取的任何时间变化。体素 SPM 分析显示，在 13 个月时首次出现皮质结合增加的迹象，并证实了额叶和颞叶皮质的结合逐渐增加（未校正 P <0.001）至 20 个月。SUV 与斑块负荷百分比强烈相关（R=0.95，P<0.001）。
在使用新型β-淀粉样蛋白示踪剂（18）F-氟比他滨的 AD 小鼠模型的首次纵向 PET 研究中，敏感地监测了 APP-Swe 小鼠大脑中淀粉样蛋白形成的时间和空间进展。该方法应为 AD 治疗的新型治疗方法的临床前测试提供手段。
