Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Nuclear Medicine, University Hospital Heidelberg, Germany.
Division of Medical Image Computing, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Radiation Oncology, University Hospital Heidelberg, Germany.
Eur J Radiol. 2020 Jun;127:109021. doi: 10.1016/j.ejrad.2020.109021. Epub 2020 Apr 20.
Targeting Fibroblast Activation Protein (FAP) is a new approach for glioblastoma imaging. In a recent pilot study glioblastomas showed elevated tracer uptake with high intratumoral heterogeneity in projection on the corresponding T2w/FLAIR and contrast enhanced MRI lesions. In this study, we correlated FAP-specific signaling with apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) signals in MRI to further characterize the significance of FAP uptake.
Clinical PET/CT scans of 13 glioblastoma patients were performed post i. v. administration of Ga-labelled-FAP-specific tracer molecules. PET- and corresponding MRI-scans were co-registrated. 3d volumetric segmentations were performed of T2w/FLAIR lesions and contrast enhancing lesions within co-registrated MRI slides. Signal intensity values of FAP-specific PET signaling, ADC and rCBV were analyzed for their pixel wise correlation in each patient. Pooled estimates of the correlation coefficients were calculated by using the Fisher z-transformation.
FAP-specific PET signals showed a moderately positive correlation with rCBV values which is more pronounced within the T2w/FLAIR lesion (pooled correlation 0,229) than in the contrast enhancing tumor region (pooled correlation 0.09). FAP-specific PET signals showed no correlation with ADC values.
The moderately positive correlation of FAP-specific signals with rCBV values in MRI indicates that FAP-signaling is not independent from perfusion, but also does not only reflect intratumoral perfusion differences. The missing correlation of FAP-specific signals with ADC indicates that FAP-specific imaging does not reflect cell density, but the spot-like expression of FAP in glioblastomas. The clinical value of FAP-specific imaging needs further investigation.
靶向成纤维细胞激活蛋白（FAP）是一种新的脑胶质瘤成像方法。在最近的一项试点研究中，脑胶质瘤在 T2w/FLAIR 和对比增强 MRI 病变的相应投射上显示出放射性示踪剂摄取增加，且肿瘤内异质性高。在这项研究中，我们将 FAP 特异性信号与 MRI 中的表观扩散系数（ADC）和相对脑血容量（rCBV）信号相关联，以进一步表征 FAP 摄取的意义。
对 13 例脑胶质瘤患者进行静脉注射 Ga 标记的 FAP 特异性示踪剂后进行临床 PET/CT 扫描。将 PET 和相应的 MRI 扫描进行配准。在配准的 MRI 切片中，对 T2w/FLAIR 病变和对比增强病变进行 3D 容积分割。对每位患者的 FAP 特异性 PET 信号、ADC 和 rCBV 的信号强度值进行分析，以确定它们在像素水平上的相关性。使用 Fisher z 变换计算相关系数的合并估计值。
FAP 特异性 PET 信号与 rCBV 值呈中度正相关，在 T2w/FLAIR 病变中更为明显（合并相关系数 0.229），而在对比增强肿瘤区域中则不明显（合并相关系数 0.09）。FAP 特异性 PET 信号与 ADC 值无相关性。
FAP 特异性信号与 MRI 中 rCBV 值的中度正相关表明，FAP 信号与灌注并不独立，也不仅仅反映肿瘤内灌注差异。FAP 特异性信号与 ADC 无相关性表明，FAP 特异性成像不反映细胞密度，而是反映 FAP 在脑胶质瘤中的点状表达。FAP 特异性成像的临床价值需要进一步研究。
