Silberbauer Leo R, Gryglewski Gregor, Berroterán-Infante Neydher, Rischka Lucas, Vanicek Thomas, Pichler Verena, Hienert Marius, Kautzky Alexander, Philippe Cecile, Godbersen Godber M, Vraka Chrysoula, James Gregory M, Wadsak Wolfgang, Mitterhauser Markus, Hacker Marcus, Kasper Siegfried, Hahn Andreas, Lanzenberger Rupert
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria.
Front Mol Neurosci. 2019 Jul 12;12:172. doi: 10.3389/fnmol.2019.00172. eCollection 2019.
quantification of the serotonin transporter (SERT) guided our understanding of many neuropsychiatric disorders. A recently introduced bolus plus constant infusion protocol has been shown to allow the reliable determination of SERT binding with reduced scan time. In this work, the outcomes of two methods, a bolus injection paradigm on a GE PET camera, and a bolus plus infusion paradigm on a combined Siemens PET/MR camera were compared. A total of seven healthy subjects underwent paired PET and paired PET/MR scans each with intravenous double-blind application of 7.5 mg citalopram or saline in a randomized cross-over study design. While PET scans were performed according to standard protocols and non-displaceable binding potentials (BP) were calculated using the multi-linear reference tissue model, during PET/MR measurements [C]DASB was applied as bolus plus constant infusion, and BP was calculated using the steady state method and data acquired at tracer equilibrium. Occupancies were calculated as the relative decrease in BP between saline and citalopram scans. During placebo scans, a mean difference in BP of -0.08 (-11.71%) across all ROIs was found between methods. PET/MR scans resulted in higher BP estimates than PET scans in all ROIs except the midbrain. A mean difference of -0.19 (-109.40%) across all ROIs between methods was observed for citalopram scans. PET/MR scans resulted in higher BP estimates than PET scans in all ROIs. For occupancy, a mean difference of 23.12% (21.91%) was observed across all ROIs. PET/MR scans resulted in lower occupancy compared to PET scans in all ROIs except the temporal cortex. While for placebo, BP of high-binding regions (thalamus and striatum) exhibited moderate reliability (ICC = 0.66), during citalopram scans ICC decreased (0.36-0.46). However, reliability for occupancy remained high (0.57-0.82). Here, we demonstrated the feasibility of reliable and non-invasive SERT quantification using a [C]DASB bolus plus constant infusion protocol at a hybrid PET/MR scanner, which might facilitate future pharmacological imaging studies. Highest agreement with established methods for quantification of occupancy and SERT BP at baseline was observed in subcortical high-binding regions.
血清素转运体（SERT）的定量分析有助于我们对多种神经精神疾病的理解。最近引入的团注加持续输注方案已被证明能够在缩短扫描时间的情况下可靠地测定SERT结合情况。在这项研究中，比较了两种方法的结果，一种是在GE PET相机上采用团注注射范式，另一种是在西门子PET/MR联合相机上采用团注加输注范式。在一项随机交叉研究设计中，共有7名健康受试者接受了PET和PET/MR配对扫描，每次扫描均通过静脉双盲注射7.5毫克西酞普兰或生理盐水。PET扫描按照标准方案进行，并使用多线性参考组织模型计算不可置换结合电位（BP）；在PET/MR测量过程中，[C]DASB作为团注加持续输注给药，并使用稳态方法和示踪剂平衡时获取的数据计算BP。占有率通过计算生理盐水扫描和西酞普兰扫描之间BP的相对下降来得出。在安慰剂扫描期间，两种方法在所有感兴趣区域（ROI）的BP平均差异为-0.08（-11.71%）。除中脑外，PET/MR扫描在所有ROI中得出的BP估计值均高于PET扫描。在西酞普兰扫描中，两种方法在所有ROI中的平均差异为-0.19（-109.40%）。PET/MR扫描在所有ROI中得出的BP估计值均高于PET扫描。对于占有率，所有ROI的平均差异为23.12%（21.91%）。除颞叶皮质外，PET/MR扫描在所有ROI中的占有率均低于PET扫描。在安慰剂扫描时，高结合区域（丘脑和纹状体）的BP显示出中等可靠性（组内相关系数ICC = 0.66），在西酞普兰扫描期间ICC降低（0.36 - 0.46）。然而，占有率的可靠性仍然很高（0.57 - 0.82）。在此，我们证明了在混合PET/MR扫描仪上使用[C]DASB团注加持续输注方案进行可靠且无创SERT定量分析的可行性，这可能会促进未来的药理成像研究。在皮质下高结合区域观察到与既定的占有率和基线SERT BP定量方法的最高一致性。
