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

¹ PET Center, Division of Nuclear Medicine, University Hospital, Zürich, Switzerland; ² Department of Oncology, University Hospital, Zürich, Switzerland; ³ Department of Neurosurgery, Cantonal Hospital, Aarau, Switzerland; ⁴ Department of Oncology and Hematology, Cantonal Hospital, Aarau, Switzerland; and ⁵ Department of Neurology, Cantonal Hospital, Aarau, Switzerland

Correspondence: For correspondence contact: Ulrich Roelcke, MD, Department of Neurology, Cantonal Hospital, CH 5001 Aarau, Switzerland. E-mail: roelcke{at}ksa.ch

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 = 0.771, P < 0.01). The volumes of increased CBF and ¹⁸F-FET uptake spatially coincided and were also correlated ( = 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.

Key Words: low-grade glioma • fluoro-ethyl-L-tyrosine • blood flow • positron emission tomography

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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