18F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

doi:10.1016/j.ejrad.2008.04.018

European Journal of Radiology

Volume 71, Issue 2, August 2009, Pages 242-248

https://doi.org/10.1016/j.ejrad.2008.04.018 Get rights and content

Abstract

Background and purpose

¹⁸F-FDOPA PET demonstrates higher sensitivity and specificity for gliomas than traditional [¹⁸F] FDG PET imaging. However, PET provides limited anatomic localization. The purpose of this study was to determine whether ¹⁸F-FDOPA PET/MRI fusion can provide precise anatomic localization of abnormal tracer uptake and how this activity corresponds to MR signal abnormality.

Methods

Two groups of patients were analyzed. Group I consisted of 21 patients who underwent ¹⁸F-FDOPA PET and MRI followed by craniotomy for tumor resection. Group II consisted of 70 patients with a pathological diagnosis of glioma that had ¹⁸F-FDOPA PET and MRI but lacked additional pathologic follow-up. Fused ¹⁸F-FDOPA PET and MRI images were analyzed for concordance and correlated with histopathologic data.

Results

Fusion technology facilitated precise anatomical localization of ¹⁸F-FDOPA activity. In group I, all 21 cases showed pathology-confirmed tumor. Of these, ¹⁸F-FDOPA scans were positive in 9/10 (90%) previously unresected tumors, and 11/11 (100%) of recurrent tumors. Of the 70 patients in group II, concordance between MRI and ¹⁸F-FDOPA was found in 49/54 (90.1%) of patients with sufficient follow-up; in the remaining 16 patients concordance could not be determined due to lack of follow-up. ¹⁸F-FDOPA labeling was comparable in both high- and low-grade gliomas and identified both enhancing and non-enhancing tumor equally well. In some cases, ¹⁸F-FDOPA activity preceded tumor detection on MRI.

Conclusion

¹⁸F-FDOPA PET/MRI fusion provides precise anatomic localization of tracer uptake and labels enhancing and non-enhancing tumor well. In a small minority of cases, ¹⁸F-FDOPA activity may identify tumor not visible on MRI.

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.

Section snippets

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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FDOPA-PET and MRI fusion provided anatomical localization precision of abnormal FDOPA-PET activity, and the concordance between both enhancing and nonenhancing lesions on MRI and increased FDOPA-PET uptake was approximately 90 %. FDOPA-PET could identify tumors not visible on MRI and was able to distinguish recurrent nonenhancing tumors from other causes of T2 signal changes on MRI (Ledezma et al., 2009). A meta-analysis of 15 articles and 640 patients with primary brain tumors reported that FDOPA-PET was more effective than FET-PET (p = 0.015) (Yu et al., 2018), another amino tracer that was used and studied.
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18F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

Abstract

Background and purpose

Methods

Results

Conclusion

Introduction

Section snippets

Patients

18F-FDOPA PET detects most gliomas

Discussion

Conclusion

Neuroimaging Clin N Am

Biochem Pharmacol

Int J Rad Appl Instrum B

Surg Neurol

Relevance of positron emission tomography (PET) in oncology

Strahlenther Onkol

Positron emission tomography using [18F] fluorodeoxyglucose in brain tumors: a powerful diagnostic and prognostic tool

Invest Radiol

Fluorine-18 deoxyglucose and false-+ results: a major problem in the diagnostics of oncological patients

Eur J Nucl Med

Differentiating recurrent tumor from radiation necrosis: time for re-evaluation of positron emission tomography?

AJNR Am J Neuroradiol

Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants

Radiographics

FDG PET of infection and inflammation

Radiographics

PET tracers for imaging of the dopaminergic system

Curr Med Chem

The metabolic anatomy of Parkinson's disease: complementary [18F]fluorodeoxyglucose and [18F]fluorodopa positron emission tomographic studies

Mov Disord

Dopamine visualized in the basal ganglia of living man

Nature

¹⁸F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

¹⁸F-FDOPA PET detects most gliomas

Positron emission tomography using [¹⁸F] fluorodeoxyglucose in brain tumors: a powerful diagnostic and prognostic tool

The metabolic anatomy of Parkinson's disease: complementary [¹⁸F]fluorodeoxyglucose and [¹⁸F]fluorodopa positron emission tomographic studies