¹¹C‐methionine uptake and intraoperative 5‐aminolevulinic acid‐induced fluorescence as separate index markers of cell density in glioma

Abstract

BACKGROUND:The extent of tumor resection is acknowledged as 1 of the prognostic factors for glioma. 5-Aminolevulinic acid (5-ALA)-induced fluorescence guidance and neuronavigation integrated with 11 C-methionine positron emission tomography (PET) are widely utilized under the expectation of improving the extent of resection. These 2 novel approaches are beneficial for glioma resections, and the combination of these approaches appears rational. However, biological characteristics reflecting 5-ALA-induced fluorescence and 11 C-methionine uptake have not been clearly elucidated, and studies about the relationship between 5-ALA-induced fluorescence and 11 C-methionine uptake have been limited. The present study aimed to clarify this issue. METHODS: Data from 11 consecutive patients harboring astrocytic tumors were analyzed: 2 grade II and 2 grade III, and 7 grade IV tumors were included. Thirty samples from these patients were obtained from the relative periphery of each tumor. Relationships among histology, 5-ALA-induced fluorescence and 11 C-methionine uptake were analyzed by stereotactic sampling and image analysis. RESULTS:Uptake of 11 C-methionine correlated with cell density (R 2 ¼ 0.322, P ¼ .0059). Cell density was higher in fluorescence-positive areas than in negative areas (2760 AE 1080 vs 1450 AE 1380/mm 2 , P ¼ .0132). Although both 11 C-methionine uptake and fluorescence seemed to correlate with cell density, no significant difference in 11 C-methionine uptake was seen between fluorescence-positive and -negative areas (P ¼ .367). Multiple linear regression analysis revealed 11 C-methionine uptake and 5-ALA-induced fluorescence as independent indices for tumor cell density. CONCLUSIONS:These results indicate that 5-ALA fluorescence and 11 C-methionine PET image are separate index markers for cytoreduction surgery of gliomas.

A prospective Phase II clinical trial of 5-aminolevulinic acid to assess the correlation of intraoperative fluorescence intensity and degree of histologic cellularity during resection of high-grade gliomas

“…18 Higher levels of fluorescence have higher levels of ALA-induced protoporphyrin concentration and correlate strongly with increasing malignancy (histopathological score) and tissue proliferation. 2,31 To our knowledge, there are only 2 studies that have directly addressed the relationship of intraoperative ALA fluorescence intensity with degree of cellularity.…”

A Novel PET Index, 18F-FDG–11C-Methionine Uptake Decoupling Score, Reflects Glioma Cell Infiltration

“…Because the amount of accumulated 11 C-methionine is correlated with the amount of amino acid transporters within the lesion, the magnitude of 11 C-methionine accumulation shows a positive correlation with glioma cell density (7). Our previous reports have suggested that this assumption is true to some extent in both tumor-core and tumor-infiltrative lesions, making 11 Cmethionine PET a reliable imaging modality for glioma cell detection (5,6). This correlation, however, is not well preserved in tumor-infiltrative lesions (5).…”

“…Different imaging methods, such as diffusion tensor MRI (DTI) and amino acid PET, have been proposed to overcome this issue (1)(2)(3)(5)(6)(7). The ability of these 2 imaging modalities to characterize microstructural and metabolic tissue information has led to their use for glioma imaging.…”

“…11 C-labeled methionine is the most commonly used amino acid tracer, and various studies have confirmed its clinical value in assessing the biologic characteristics of glioma tissue (5)(6)(7)9,10). In addition, the magnitude of tracer accumulation has been shown to reflect tumor cell density within the tumor core of glioma (6).…”

Preclinical Characterization of 5-Amino-4-Oxo-[6-11C]Hexanoic Acid as an Imaging Probe to Estimate Protoporphyrin IX Accumulation Induced by Exogenous Aminolevulinic Acid

“…Several studies were undertaken to detect regions of ALA-induced PpIX accumulation in malignant tumors with noninvasive tomographic imaging such as gadolinium-enhanced MR imaging (14) or PET with L-[methyl-11 C]-methionine ( 11 C-MET) (15) (12). Those studies showed that there were some differences between gadoliniumenhanced MR imaging or 11 C-MET or 18 F-FET PET imaging and PpIX accumulation (12,15), because these diagnostic images provided information different from PpIX accumulation-that is, gadolinium-enhanced MR imaging and PET with 11 C-MET or 18 F-FET reflect the blood-brain barrier breakdown (16) or amino acid metabolism (17) but not PpIX accumulation. Therefore, a new noninvasive imaging method based on the mechanism of PpIX accumulation is needed.…”