Spatial Heterogeneity of Low-Grade Gliomas at the Capillary Level: A PET Study on Tumor Blood Flow and Amino Acid Uptake
Spatial Heterogeneity of Low-Grade Gliomas at the Capillary Level: A PET Study on Tumor Blood Flow and Amino Acid Uptake
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毛细血管水平低级别胶质瘤的空间异质性：肿瘤血流和氨基酸摄取的 PET 研究
DOI：
10.2967/jnumed.106.038489
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发表时间：
2007
影响因子：
9.3
通讯作者：
U. Roelcke
中科院分区：
文献类型：
--
作者：
M. Wyss;S. Hofer;M. Hefti;E. Bärtschi;Catrina Uhlmann;V. Treyer;U. Roelcke
许多低级别胶质瘤（世界卫生组织II级）对化疗有反应。脑血流量（CBF）和微血管密度可能是药物输送的关键。我们使用PET与18F-fluoro-ethyl-1-tyrosine（FET）来测量位于脑毛细血管的氨基酸载体的空间分布，并使用15 O-H2O来测量肿瘤CBF。方法：对17例低级别胶质瘤患者进行研究。使用感兴趣区域（ROI）分析来量化肿瘤示踪剂摄取，其被归一化为小脑摄取（肿瘤-小脑比率）。“活性”肿瘤定义为放射性浓度至少为小脑活性的110%的肿瘤。该阈值提供了活性肿瘤体积、总体和峰值肿瘤CBF以及18F-FET摄取的测量。应用示踪ROI来创建跨肿瘤和脑的CBF和18F-FET摄取的体素分布。标准MRI序列用于空间相关性。结果：17例肿瘤中有14例表现为整体CBF和18F-FET摄取增加。18F-FET的活动肿瘤体积范围为3至270 cm 3，CBF的活动肿瘤体积范围为1至41 cm 3。肿瘤中18 F-FET的总体摄取与CBF的增加相对应（斯皮尔曼等级ρ = 0.771，P < 0.01）。CBF增加量与18F-FET摄取量在空间上一致，且相关性较好（ρ = 0.944，P < 0.01）。示踪ROI显示，无论肿瘤周边18F-FET摄取增加，CBF增加更多地局限于肿瘤中心。在个体肿瘤内，存在空间异质性。浸润胼胝体的特定肿瘤在该肿瘤区域显示低CBF和18F-FET摄取。PET观察到的模式没有反映在肿瘤的MRI上，所有这些都表现为均匀的非钆增强病变。结论：低级别胶质瘤在氨基酸摄取和脑血流量分布上具有异质性。两者在肿瘤中心偶联。在肿瘤周围，即肿瘤浸润周围脑的地方，CBF可能较低，而与18F-FET摄取增加无关。一项正在进行的研究正在调查化疗对这些观察结果的影响。
Many low-grade gliomas (World Health Organization grade II) respond to chemotherapy. Cerebral blood flow (CBF) and microvessel density may be critical for drug delivery. We used PET with 18F-fluoro-ethyl-l-tyrosine (FET) to measure the spatial distribution of the amino acid carrier, which is located at the brain capillaries, and 15O-H2O to measure tumor CBF. Methods: Seventeen patients with low-grade glioma were studied. Region-of-interest (ROI) analysis was used to quantify tumor tracer uptake, which was normalized to cerebellar uptake (tumor-to-cerebellum ratio). “Active” tumor was defined as tumor having a radioactivity concentration that was at least 110% of the cerebellar activity. This threshold provided measures of active tumor volume, global and peak tumor CBF, and 18F-FET uptake. Trace ROIs were applied to create voxelwise profiles of CBF and 18F-FET uptake across tumor and brain. Standard MRI sequences were used for spatial correlations. Results: Fourteen of 17 tumors showed increased global CBF and 18F-FET uptake. Active tumor volumes ranged between 3 and 270 cm3 for 18F-FET and between 1 and 41 cm3 for CBF. Global 18F-FET uptake in tumors corresponded to CBF increases (Spearman rank ρ = 0.771, P < 0.01). The volumes of increased CBF and 18F-FET uptake spatially coincided and were also correlated (ρ = 0.944, P < 0.01). Trace ROIs showed that irrespective of increased 18F-FET uptake at the tumor periphery, CBF increases were more confined to the tumor center. Within individual tumors, spatial heterogeneity was present. Particular tumors infiltrating the corpus callosum showed low CBF and 18F-FET uptake in this tumor region. The patterns observed with PET were not reflected on MRI of the tumors, all of which presented as homogeneous non–gadolinium-enhancing lesions. Conclusion: Low-grade gliomas are heterogeneous tumors with regard to the distribution of amino acid uptake and CBF. Both are coupled in the tumor center. At the tumor periphery, where tumor infiltration of surrounding brain occurs, CBF may be low irrespective of increased 18F-FET uptake. An ongoing study is investigating the effect of chemotherapy on these observations.