Spatial Heterogeneity of Low-Grade Gliomas at the Capillary Level: A PET Study on Tumor Blood Flow and Amino Acid Uptake

Journal of Nuclear Medicine

Esther Bärtschi¹  Valerie Treyer¹  Catrina Uhlmann¹  Matthias T. Wyss¹  Ulrich Roelcke¹  Martin Hefti¹  Silvia Hofer¹ 

关键词: low-grade glioma;    fluoro-ethyl-l-tyrosine;    blood flow;    positron emission tomography;   

DOI  :  10.2967/jnumed.106.038489

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown