Department of Neurology.
Department of Psychiatry and Behavioral Sciences.
AIDS. 2023 Jul 15;37(9):1419-1424. doi: 10.1097/QAD.0000000000003572. Epub 2023 Apr 5.
Neuroimmune activation is a putative driver of cognitive impairment in people with HIV (PWH), even in the age of modern antiretroviral therapy. Nevertheless, imaging of the microglial marker, the 18 kDa translocator protein (TSPO), with positron emission tomography (PET) in treated PWH has yielded inconclusive findings. One potential reason for the varied TSPO results is a lack of cell-type specificity of the TSPO target.
[ 11 C]CPPC, 5-cyano- N -(4-(4-[ 11 C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxaminde, is a radiotracer for use with PET to image the colony stimulating factor 1 receptor (CSF1R). The CSF1R is expressed on microglia and central nervous system macrophages, with little expression on other cell types. We used [ 11 C]CPPC PET in virally-suppressed- (VS)-PWH and HIV-uninfected individuals to estimate the effect sizes of higher CSF1R in the brains of VS-PWH.
Sixteen VS-PWH and 15 HIV-uninfected individuals completed [ 11 C]CPPC PET. [ 11 C]CPPC binding (V T ) in nine regions was estimated using a one-tissue compartmental model with a metabolite-corrected arterial input function, and compared between groups.
Regional [ 11 C]CPPC V T did not significantly differ between groups after age- and sex- adjustment [unstandardized beta coefficient ( B ) = 1.84, standard error (SE) = 1.18, P = 0.13]. The effect size was moderate [Cohen's d = 0.56, 95% confidence interval (CI) -0.16, 1.28), with strongest trend of higher V T in VS-PWH in striatum and parietal cortex (each P = 0.04; Cohen's d = 0.71 and 0.72, respectively).
A group difference in [ 11 C]CPPC V T was not observed between VS-PWH and HIV-uninfected individuals in this pilot, although the observed effect sizes suggest the study was underpowered to detect regional group differences in binding.
神经免疫激活被认为是 HIV 感染者（PWH）认知障碍的驱动因素，即使在现代抗逆转录病毒治疗时代也是如此。然而，用正电子发射断层扫描（PET）对治疗后的 PWH 中的小胶质细胞标志物 18 kDa 转位蛋白（TSPO）进行成像，其结果尚无定论。TSPO 结果不一致的一个潜在原因是 TSPO 靶标缺乏细胞类型特异性。
[11C]CPPC，5-氰基-N-（4-（4-[[11C]甲基哌嗪-1-基]-2-（哌啶-1-基）苯基）呋喃-2-甲酰胺，是一种用于 PET 成像集落刺激因子 1 受体（CSF1R）的放射性示踪剂。CSF1R 在小胶质细胞和中枢神经系统巨噬细胞上表达，在其他细胞类型上表达很少。我们使用[11C]CPPC PET 对病毒抑制（VS）-PWH 和 HIV 未感染者进行检测，以估计 VS-PWH 大脑中更高 CSF1R 的效应大小。
16 名 VS-PWH 和 15 名 HIV 未感染者完成了[11C]CPPC PET。使用带有代谢物校正的动脉输入函数的单组织隔室模型估计了 9 个区域的[11C]CPPC 结合（V T），并在组间进行了比较。
在年龄和性别调整后，两组间的局部[11C]CPPC V T 无显著差异[未标准化β系数（B）=1.84，标准误差（SE）=1.18，P=0.13]。效应大小为中等[Cohen's d=0.56，95%置信区间（CI）-0.16，1.28]，在纹状体和顶叶皮层中，VS-PWH 的 V T 趋势更强（均 P=0.04；Cohen's d=0.71 和 0.72）。
在这项初步研究中，我们未观察到 VS-PWH 与 HIV 未感染者之间[11C]CPPC V T 存在组间差异，尽管观察到的效应大小表明该研究检测结合的局部组间差异的能力不足。
