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Validation of the Semiquantitative Static SUVR Method for 18F-AV45 PET by Pharmacokinetic Modeling with an Arterial Input Function
The Journal of Nuclear Medicine ( IF 9.3 ) Pub Date : 2017-09-01 , DOI: 10.2967/jnumed.116.184481
Julie Ottoy , Jeroen Verhaeghe , Ellis Niemantsverdriet , Leonie Wyffels , Charisse Somers , Ellen De Roeck , Hanne Struyfs , Femke Soetewey , Steven Deleye , Tobi Van den Bossche , Sara Van Mossevelde , Sarah Ceyssens , Jan Versijpt , Sigrid Stroobants , Sebastiaan Engelborghs , Steven Staelens

Increased brain uptake of 18F-AV45 visualized by PET is a key biomarker for Alzheimer disease (AD). The SUV ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (VT) to assess cross-sectional differences in plaque load. Methods: Dynamic 60-min 18F-AV45 (291 ± 67 MBq) and 1-min 15O-H2O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD, 15 amnestic mild cognitive impairment (aMCI), and 10 cognitively healthy controls (HCs). 18F-AV45 VT was determined from 2-tissue-compartment modeling using a metabolite-corrected plasma input function. Static SUVR was calculated at 50–60 min after injection, using either cerebellar gray matter (SUVRCB) or whole subcortical white matter (SUVRWM) as the reference. Additionally, whole cerebellum, pons, centrum semiovale, and a composite region were examined as alternative references. Blood flow was quantified by 15O-H2O SUV. Data are presented as mean ± SEM. Results: There was rapid metabolization of 18F-AV45, with only 35% of unchanged parent remaining at 10 min. Compared with VT, differences in cortical Aβ load between aMCI and AD were overestimated by SUVRWM (+4% ± 2%) and underestimated by SUVRCB (−10% ± 2%). VT correlated better with SUVRWM (Pearson r: from 0.63 for posterior cingulate to 0.89 for precuneus, P < 0.0001) than with SUVRCB (Pearson r: from 0.51 for temporal lobe [P = 0.002] to 0.82 for precuneus [P < 0.0001]) in all tested regions. Correlation results for the alternative references were in between those for CB and WM. 15O-H2O data showed that blood flow was decreased in AD compared with aMCI in cortical regions (−5% ± 1%) and in the reference regions (CB, −9% ± 8%; WM, −8% ± 8%). Conclusion: Increased brain uptake of 18F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVRWM is better correlated with VT and more closely reflects VT differences between aMCI and AD than SUVRCB.



中文翻译:

具有动脉输入功能的药代动力学模型对18 F-AV45 PET半定量静态SUVR方法的验证

PET显示的18 F-AV45的脑摄取增加是阿尔茨海默病(AD)的关键生物标志物。SUV比(SUVR)被广泛用于量化,但会因参考区域的选择和脑血流量的变化而变化。在这里,我们根据金标准分布体积(V T)验证SUVR方法,以评估斑块负荷的横截面差异。方法:在35位年龄相匹配的老年受试者中进行了60分钟的动态18分钟F-AV45(291±67 MBq)和1分钟的15 O-H 2 O(370 MBq)扫描,其中包括10例可能的AD,15例轻度轻度认知障碍( aMCI)和10个认知健康对照(HCs)。18 F-AV45 V使用代谢物校正的血浆输入函数从2组织隔室模型确定T。注射后50-60分钟,以小脑灰质(SUVR CB)或整个皮质下白质(SUVR WM)作为参考,计算静态SUVR 。另外,检查了整个小脑,脑桥,中心半卵和一个复合区域作为替代参考。通过15 O-H 2 O SUV定量血流。数据表示为平均值±SEM。结果:18 F-AV45快速代谢,在10分钟时仅保留35%的未改变亲本。与V T比较,SUVR WM(+ 4%±2%)高估了aMCI和AD之间的皮质Aβ负荷差异,而SUVR CB(-10%±2%)低估了皮质Aβ负荷。V T与SUVR WM(Pearson r:后扣带的0.63到足前神经的0.89,P <0.0001)的相关性比SUVR CB(Pearson r:从颞叶的0.51 [ P = 0.002]到足前神经的0.82 [ P < 0.0001])。替代参考的相关结果介于CB和WM之间。15 O-H 2O数据显示,与aMCI相比,在皮质区域(−5%±1%)和参考区域(CB,−9%±8%; WM,−8%±8%),AD的血流减少。结论:通过简化的静态SUVR协议评估的18 F-AV45的大脑摄取增加并未真正反映Aβ负荷。但是,SUVR WM与V T的相关性更好,并且比SUVR CB更能反映aMCI和AD之间的V T差异。

更新日期:2017-09-05
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