Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study.
Specific and non-specific binding of a tracer for the translocator-specific protein in schizophrenia: an [11C]-PBR28 blocking study.
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DOI：
10.1007/s00259-021-05327-x
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发表时间：
2021-10
影响因子：
9.1
通讯作者：
Howes OD
中科院分区：
文献类型：
--
作者：
Marques TR;Veronese M;Owen DR;Rabiner EA;Searle GE;Howes OD
线粒体18-kDa转运蛋白（TSPO）由活化的小胶质细胞表达，正电子发射断层扫描能够测量脑中的TSPO水平。在精神分裂症中的发现已显示出根据所使用的结果测量而变化，并且TSPO结果中的这种差异可以通过精神分裂症中较低的不可置换结合（VND）来解释，这可能掩盖特异性结合的增加。在这项研究中，我们使用TSPO配体XBD 173来阻断TSPO放射性配体[11 C]-PBR 28，并使用占用图来量化精神分裂症患者的VND。本研究共招募了7例诊断为精神分裂症的患者。每名患者接受两次单独的[11 C] PBR 28 PET扫描，一次在基线，一次在TSPO配体XBD 173给药后。所有患者都是TSPO基因的高亲和力结合者（HAB）。我们使用占用图来量化不可置换成分（VND），使用2 TCM动力学估计，有和没有血管校正。最后，我们使用SIME方法计算了单个受试者水平的VND。所有患者在给予XBD 173后均显示[11 C] PBR 28摄取的整体和全身性降低。将所有患者的VND限制为相等，估计群体VND为1.99 mL/cm 3（95% CI 1.90 - 2.08）。当我们使用血管校正时，TSPO占用分数保持相似。在精神分裂症患者中，[11 C] PBR 28信号的实质性成分代表与TSPO的特异性结合。此外，精神分裂症患者的VND与以前报道的健康对照相似。这些结果表明，精神分裂症患者和健康对照者之间非特异性结合的变化不能解释这种疾病中PET结果的差异。在线版本包含补充材料，可通过10.1007/s 00259 -021-05327-x获得。
The mitochondrial 18-kDa translocator protein (TSPO) is expressed by activated microglia and positron emission tomography enables the measurement of TSPO levels in the brain. Findings in schizophrenia have shown to vary depending on the outcome measure used and this discrepancy in TSPO results could be explained by lower non-displaceable binding (VND) in schizophrenia, which could obscure increases in specific binding. In this study, we have used the TSPO ligand XBD173 to block the TSPO radioligand [11C]-PBR28 and used an occupancy plot to quantify VND in patients with schizophrenia. A total of 7 patients with a diagnosis of schizophrenia were recruited for this study. Each patient received two separate PET scans with [11C]PBR28, one at baseline and one after the administration of the TSPO ligand XBD173. All patients were high-affinity binders (HABs) for the TSPO gene. We used an occupancy plot to quantify the non-displaceable component (VND) using 2TCM kinetic estimates with and without vascular correction. Finally we computed the VND at a single subject level using the SIME method. All patients showed a global and generalized reduction in [11C]PBR28 uptake after the administration of XBD173. Constraining the VND to be equal for all patients, the population VND was estimated to be 1.99 mL/cm3 (95% CI 1.90 to 2.08). When we used vascular correction, the fractional TSPO occupancy remained similar. In schizophrenia patients, a substantial component of the [11C]PBR28 signal represents specific binding to TSPO. Furthermore, the VND in patients with schizophrenia is similar to that previously reported in healthy controls. These results suggest that changes in non-specific binding between schizophrenia patients and healthy controls do not account for discrepant PET findings in this disorder. The online version contains supplementary material available at 10.1007/s00259-021-05327-x.
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影响因子：
3.2
作者：
Coughlin JM;Wang Y;Ma S;Yue C;Kim PK;Adams AV;Roosa HV;Gage KL;Stathis M;Rais R;Rojas C;McGlothan JL;Watkins CC;Sacktor N;Guilarte TR;Zhou Y;Sawa A;Slusher BS;Caffo B;Kassiou M;Endres CJ;Pomper MG
通讯作者：
Pomper MG
DOI：
10.1007/s00259-015-3149-8
发表时间：
2016-01-01
影响因子：
9.1
作者：
Collste, K.;Forsberg, A.;Cervenka, S.
通讯作者：
Cervenka, S.
影响因子：
15.1
作者：
De Picker, Livia;Ottoy, Julie;Morrens, Manuel
通讯作者：
Morrens, Manuel
影响因子：
5.7
作者：
Edison, Paul;Brooks, David J.;Hinz, Rainer
通讯作者：
Hinz, Rainer
影响因子：
6.3
作者：
LASSEN, NA;BARTENSTEIN, PA;ANDERSEN, JV
通讯作者：
ANDERSEN, JV