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Association of F18-fluoro-ethyl-tyrosin uptake and 5-aminolevulinic acid-induced fluorescence in gliomas

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Abstract

Purpose

Malignant gliomas are highly infiltrative tumours with a fatal prognosis. F18-fluoroethyl-tyrosine (FET)-positron emission tomography (PET) often reveals a broader extension of these tumours compared with contrast-enhanced magnetic resonance imaging (MRI). Complete resection of the contrast-enhancing lesion is aspired. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) improved the extent of resection. In this study, we investigated whether the FET uptake correlates with the extent of resection using 5-ALA-induced fluorescence.

Methods

Thirteen patients who underwent preoperative and postoperative MRI, FET-PET and fluorescence-guided neuronavigated resection were included in this study. The areas in which intraoperative fluorescence terminated the resection were marked. After fusion of PET and MRI, the standardized uptake value (SUV) of FET related to normal brain (SUVR) was measured in regions of interest corresponding to resected and remaining tissue, respectively. Receiver-operating characteristic (ROC) curve analysis determined the optimal threshold of the relative SUV anticipating 5-ALA-induced fluorescence.

Results

During resection a vivid fluorescence was present in all patients. Histology revealed glioblastomas in 11 cases, an anaplastic astrocytoma in one case and a low-grade astrocytoma in one case. The median FET SUVR was higher in areas corresponding to the fluorescent tumour compared with the non-fluorescent normal brain (2.321 vs 1.142, p < 0.0001, t-test). A SUVR greater than 1.374 predicted the fluorescence with a sensitivity of 0.87 [95% confidence interval (CI): 0.74–0.94] and a specificity of 0.94 (CI: 0.84–0.99). The area under the ROC curve was 0.9656 (CI: 0.9364–0.9948).

Conclusions

FET uptake predicts the 5-ALA-induced fluorescence in glioma patients. Thus, FET-PET provides useful information for planning glioma resection.

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Correspondence to Florian Stockhammer.

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Comment

The authors present a retrospective study on a limited series of patients affected by gliomas in order to assess the concordance of preoperative FET-PET uptake values and intraoperative 5-ALA-induced fluorescence data. Standard MRI sequences are usually used for surgical planning, even though they are only able to partially detect the extent and, even less, the biological features of gliomas. Therefore, every effort to investigate the relationships between preoperative images and intraoperative data is welcome in order to achieve a more effective use of surgery in neuro-oncology. In this series the authors show that preoperative FET-PET is an accurate predictor of 5-ALA fluorescence-based tumour resection. Consequently, it can represent a useful tool to plan and conduct surgery. Nevertheless, we have to remember that both techniques are able to primarily detect the amount of tumoural cellularity and for this reason they are able to show only one aspect of the tumour biology, which is usually heterogeneous in this kind of tumour (consider, for example, the variable degree of necrosis and neoangiogenesis). It would be interesting if future prospective studies could focus on the relationships in selected different points of the tumour between FET-PET data, intraoperative 5-ALA data and histopathological data. This would be useful, above all, when surgery on recurrent gliomas is considered. The observation of vivid 5-ALA uptake in their case of low-grade glioma is intriguing and warrants further investigations.

Domenico d’Avella

Alessandro Della Puppa

Padova, Italy

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Stockhammer, F., Misch, M., Horn, P. et al. Association of F18-fluoro-ethyl-tyrosin uptake and 5-aminolevulinic acid-induced fluorescence in gliomas. Acta Neurochir 151, 1377–1383 (2009). https://doi.org/10.1007/s00701-009-0462-7

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