18F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience
Introduction
CT and MRI are the standard anatomic imaging modalities used for the evaluation of brain tumor patients. Following treatment, the differentiation between treatment-related changes and residual or recurrent tumor can be challenging.
Given these limitations of anatomic imaging, post-treatment positron emission tomography (PET) has been advocated as a clinically useful imaging modality to differentiate treatment-related changes from recurrent tumor For these reasons, PET imaging with the glucose analogue 2-deoxy-2-[18F]fluoro-d-glucose ([18F] FDG), has proven useful as a metabolic tracer in tumor imaging [1], [2], [3].
Several important limitations of [18F] FDG PET imaging have been found, however, particularly for brain lesions [4], [5]. First of all, normal brain exhibits high background glucose metabolism, particularly in the cortex, limiting both the sensitivity and specificity of FDG-PET in differentiating brain tumor from normal brain. Secondly, since [18F] FDG PET measures increased glucose metabolism, tumors with low glucose metabolism such as low-grade gliomas may not be well visualized, thereby limiting its role in evaluating these lesions. Lastly [18F] FDG uptake is not tumor specific as false-positives occur with inflammatory and granulomatous diseases [4], [6], [7].
For these reasons, alternative PET tracers with low background brain uptake, such as the 18F-labeled amino acid 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-FDOPA), have been investigated for brain tumor imaging than [18F] FDG. 18F-FDOPA, a dopamine precursor, has been extensively used to assess the integrity of the dopaminergic system in movement disorders such as Parkinson's disease [8], [9], [10], but it has only recently shown promise in brain tumor imaging [11], [12]. As an analog to DOPA, FDOPA normally accumulates in the basal ganglia. Little FDOPA activity is present in the normal cerebral cortex or white matter. PET imaging with 18F-FDOPA has been shown to have higher sensitivity (96%) for gliomas than traditional [18F] FDG PET imaging [12]. Furthermore, unlike contrast-enhanced MRI, tumor visualization using 18F-FDOPA PET does not depend on blood–brain barrier (BBB) breakdown as this agent is believed to utilize active transport mechanisms for tissue uptake.
Metabolic imaging has increasingly been combined with anatomical imaging modalities (i.e. CT and MRI) to improve the diagnosis, treatment, and follow-up of tumors. However, no prior studies have examined 18F-FDOPA PET/MRI fusion for brain tumor assessment. In the current study, we reviewed fused 18F-FDOPA PET/MRI images and qualitatively assessed the correspondence between increased tracer uptake and evidence of tumor on MRI, and correlated these results with pathologic data.
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Patients
All patients with a pathological diagnosis of glioma who also received 18F-FDOPA scans and brain MRI or brain autopsy were selected from the UCLA brain tumor database, which has been approved by the institutional review board. All patients provided informed consent. Ninety-one patients (55 men, 36 women; mean age at time 18F-FDOPA scan of 44.9 ± 13.1 years (standard deviation, S.D.); age range, 21–79 years) with an initial or subsequent pathological diagnosis of glioma who underwent 18F-FDOPA
18F-FDOPA PET detects most gliomas
For group I patients who had no prior resection, 9/10 tumors were positive on 18F-FDOPA, and all had tumor identified by MRI and by subsequent histopathologic analysis (with pathologic diagnosis as the gold standard). For group I patients with suspected recurrent tumor, 11/11 were positive on 18F-FDOPA scans confirmed by subsequent histopathology. On MRI, 9/11 were found to be positive, 1/11 was indeterminate, and 1/11 was negative. Thus for this group of patients (n = 21), the sensitivity of 18
Discussion
To our knowledge, this is the first clinical study to systematically investigate the use of 18F-FDOPA PET/MRI fusion for brain tumor assessment. In this preliminary investigation, we show that 18F-FDOPA PET/MRI fusion works well technically, and that there is good correlation between both enhancing and non-enhancing tumor on MRI and increased 18F-FDOPA uptake.
Amino acids and their analogs are attractive for imaging brain tumors because of the high uptake in tumor tissue and low uptake in normal
Conclusion
This study demonstrates the feasibility of fusing 18F-FDOPA PET and MR images for precise anatomical localization of abnormal 18F-FDOPA PET activity. 18F-FDOPA PET labeling appears to be highly sensitive for gliomas, irrespective of tumor grade, labeling both enhancing and non-enhancing tumor equally well. In general 18F-FDOPA PET confirmed the presence of tumor apparent on MRI, although we found several examples where 18F-FDOPA PET detected tumor that was inconspicuous or not visible on MRI.
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