5‐Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement

Abstract

BACKGROUND: Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling. METHODS: 5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum 11 C-methionine positron emission tomography uptake (PET max ) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI). RESULTS: Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PET max in all patients. MIB-1 LI was significantly higher in 5-ALA-positive than in nonfluorescent areas within a given tumor. CONCLUSIONS: The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments. Cancer 2010;116:1545-52.

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

“…38 As to 11 C-methionine PET, to the best of our knowledge, only 1 report has examined the relationship between tracer uptake and 5-ALA fluorescence. 40 In that report, stereotactic sampling was performed from the area with maximum tracer uptake in gliomas showing nonsignificant contrast enhancement on MRI, and maximum uptake of 11 C-methionine was found to be higher in 5-ALA fluorescence-positive areas than in negative areas. 40 That result seems to contradict our data at first glance, but the study design was quite different between the previous and present reports.…”

“…40 In that report, stereotactic sampling was performed from the area with maximum tracer uptake in gliomas showing nonsignificant contrast enhancement on MRI, and maximum uptake of 11 C-methionine was found to be higher in 5-ALA fluorescence-positive areas than in negative areas. 40 That result seems to contradict our data at first glance, but the study design was quite different between the previous and present reports. The result reported by Widhalm et al 40 was produced by including only the area of maximum 11 C-methionine uptake, whereas our study was performed using tissues obtained from the tumor periphery, the identification of which is critical for complete tumor resection.…”

“…Several reports have compared 5-ALA-induced fluorescence with radiological findings. [37][38][39][40] A previous report showed that contrast enhancement on MRI was stronger in the fluorescence-positive area than in the fluorescence-negative area, suggesting that image signatures on preoperative MRI are predictive of intraoperative fluorescence. 37 Another 2 reports compared tracer uptake with 5-ALA-induced fluorescence.…”

Diagnóstico Fotodinâmico: Princípios E Aplicações

“…No sistema nervoso central, essa técnica vem sendo utilizada principalmente para auxiliar na coleta de amostras para biópsia, pois mostra o local exato da neoplasia (YAMAMOTO et al, 2015), e permite também, uma melhor visualização das bordas cirúrgicas na resecção de neoplasias como o linfoma primário (PCNSL) e gliomas (WIDHALM et al, 2010;EWELT et al, 2011;ROESSLER et al, 2012;COBURGER et al, 2014;YAMADA et al, 2015). GAHLEN et al (2001) realizaram um estudo utilizando o fotossensibilizador ALA, e compararam as vias intraperitoneal e endovenosa no diagnóstico de várias neoplasias.…”

Review of Neurosurgical Fluorescence Imaging Systems for Clinical Application

“…5-ALA is the most studied and the most used of the various fluorescent tumor markers for fluorescenceguided surgery. It localizes the malignant glioma more precisely for its surgical removal [23,24]. 5-ALA is a metabolite in the heme biosynthesis pathway.…”