Abstract
Simple SummaryIn malignant brain tumor surgery, precise identification of the tumor is essential. 5-Aminolevulinic acid (5-ALA) labels tumor cells with red fluorescence to facilitate tumor resection. On the other hand, the nuclear medicine imaging technique, positron emission tomography with 11C-methionine (MET-PET), can delineate tumors precisely but is not widely available. This study aimed to determine the correlation between intraoperative 5-ALA-induced fluorescence and preoperative MET-PET signals of gliomas. We quantitatively measured the fluorescence intensity from tumor samples and calculated the MET-PET uptake by the tumor. Our study showed that strong tumor fluorescence correlated with high MET-PET uptake and cellular proliferation. Our findings might be valuable to rapidly provide information on tumor biology at the time of surgery in circumstances where MET-PET is inaccessible.Background: 5-Aminolevulinic acid (5-ALA) is widely employed to assist fluorescence-guided surgery for malignant brain tumors. Positron emission tomography with 11C-methionine (MET-PET) represents the activity of brain tumors with precise boundaries but is not readily available. We hypothesized that quantitative 5-ALA-induced fluorescence intensity might correlate with MET-PET uptake in gliomas. Methods: Adult patients with supratentorial astrocytic gliomas who underwent preoperative MET-PET and surgical tumor resection using 5-ALA were enrolled in this prospective study. The regional tumor uptake of MET-PET was expressed as the ratio of standardized uptake volume max to that of the normal contralateral frontal lobe. A spectrometric fluorescence detection system measured tumor specimens’ ex vivo fluorescence intensity at 635 nm. Ki-67 index and IDH mutation status were assessed by histopathological analysis. Use of an antiepileptic drug (AED) and contrast enhancement pattern on MRI were also investigated. Results: Thirty-two patients, mostly with Glioblastoma IDH wild type (46.9%) and anaplastic astrocytoma IDH mutant (21.9%), were analyzed. When the fluorescence intensity was ranked into four groups, the strongest fluorescence group exhibited the highest mean MET-PET uptake and Ki-67 index values. When rearranged into fluorescence Visible or Non-visible groups, the Visible group had significantly higher MET-PET uptake and Ki-67 index compared to the Non-visible group. Contrast enhancement on MRI and IDH wild type tumors were more frequent among the Visible group. AED use did not correlate with 5-ALA-induced fluorescence intensity. Conclusions: In astrocytic glioma surgery, visible 5-ALA-induced fluorescence correlated with high MET-PET uptake, along with a high Ki-67 index.
Highlights
The most common primary malignant brain tumor in adults is glioblastoma (GBM)
A total of 52 adult patients with supratentorial tumors suspected of malignant glioma underwent surgical resection using 5-Aminolevulinic acid (5-ALA), and 32 patients were included in the final analysis after excluding those without adequate MET-positron emission tomography (PET) data or those diagnosed other than astrocytic tumors (Figure S1)
The results demonstrated that MET-PET uptake was significantly high in tumor specimens with quantitatively confirmed 5-ALA-induced fluorescence, suggesting a correlation between those factors in astrocytic tumors
Summary
The most common primary malignant brain tumor in adults is glioblastoma (GBM). This cancer, along with other tumor types of the same lineage (collectively adult malignant gliomas), has a dismal prognosis despite the current intensive treatment strategies [1,2]. Following the administration of the photosensitizer (or its precursor), direct illumination of excitation light with a specific wavelength invokes fluorescence emission to reveal the residual tumor’s presence intraoperatively. This technique is called photodynamic diagnosis (PDD) [8]. 5-Aminolevulinic acid (5-ALA) is most intensively studied in FGS for malignant brain tumors [9–12]. FGS with 5-ALA has been approved in many countries and proved to enhance the gross total resection of GBM [24,25]
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