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Measurement of the Extracellular Space in Brain Tumors Using ⁷⁶Br-Bromide and PET

¹ Paul Scherrer Institute, Center for Radiopharmaceutical Science, Villigen, Switzerland
² Department of Nuclear Medicine, Cantonal Hospital, Aarau, Switzerland
³ Department of Neurology, Cantonal Hospital, Aarau, Switzerland

Brain edema significantly contributes to the clinical course of human brain tumor patients. There is evidence that an enlargement of the extracellular space (ECS) is involved in the development of brain edema. Although T2-weighted magnetic resonance (T2-MR) images represent brain edema by its increased water content, they do not differentiate ECS enlargement from increased intracellular water content. Methods: On the basis of the known distribution of bromide in the ECS, we used ⁷⁶Br-bromide and PET to measure the regional ECS in 9 brain tumor patients. Transport rate constants and the distribution volume (DV) of ⁷⁶Br-bromide in normal brain and tumor were derived from dynamic PET scans and the measured ⁷⁶Br-bromide concentration in arterial plasma. We evaluated different models regarding their reliability in estimating the ECS. Results: Assuming that the DV of ⁷⁶Br-bromide represents the ECS, robust estimates were possible for all investigated regions. In normal brain, ECS was within a narrow range—for example, occipital lobe, 19.9% ± 3.1%—and was lower in 2 dexamethasone-treated patients compared with untreated patients. In 7 of 9 tumors, increased ECS ranged between 43.8% and 61.1%. ECS increases were confined to the tumor mass and did not extend into peritumoral edematous brain. Two patients with large hyperintense lesions according to T2-MR images showed normal ECS values within the lesion. Conclusion: ⁷⁶Br-Bromide PET allows a quantitative measurement of the ECS in brain edema and in normal brain. The discrepancies between lesions shown by T2-MRI and regional ECS enlargement as measured with PET challenge the concept of tumor-induced brain edema.

Key Words: brain tumor • extracellular space • pathophysiology • ⁷⁶Br-bromide PET

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