Intraoperative Fluorescence Staining of Malignant Brain Tumors Using 5-Aminofluorescein-Labeled Albumin

We analyzed the efficacy and applicability of surgery guided by 5-aminolevulinic acid (ALA) fluorescence in consecutive patients with glioblastoma multiforme (GBM). Thirty-six patients with GBM were operated on using ALA fluorescence. Resections were performed using the fluorescent light to assess the right plane of dissection. In each case, biopsies with different fluorescent quality were taken from the tumor center, from the edges, and from the surrounding tissue. These samples were analyzed separately with hematoxylin-eosin examination and immunostaining against Ki67. Tumor volume was quantified with pre-and postoperative volumetric magnetic resonance imaging. Strong fluorescence identified solid tumor with 100% positive predictive value. Invaded tissue beyond the solid tumor mass was identified by vague fluorescence with 97% positive predictive value and 66% negative predictive value, measured against hematoxylin-eosin examination. All the contrast-enhancing volume was resected in 83.3% of the patients, all patients had resection over 98% of the volume and mean volume resected was 99.8%. One month after surgery there was no mortality, and new or increased neurological morbidity was 8.2%. The fluorescence induced by 5-aminolevulinic can help to achieve near total resection of enhancing tumor volume in most surgical cases of GBM. It is possible during surgery to obtain separate samples of the infiltrating cells from the tumor border.

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“…The present data compare favorably in resection, and in particular, the correlation with the histology results is much greater [26].…”

Section: Discussionsupporting

confidence: 65%

Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

Valle¹,

Solís²,

Gastearena³

et al. 2010

J Neurooncol

185

108

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“…From a molecular-imaging perspective, ACPPDs have several advantages over other targeted fluorescent probes previously described in the literature for use in a surgical system (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Molecular fluorescence-guided surgery demands that a given probe (a), works for a wide variety of tumor types (b), offers ample signal with low background (c), binds tightly to the tumor, and (d), is not affected by the physical trauma of surgery.…”

Section: Discussionmentioning

confidence: 99%

“…We prefer targets such as MMP-2 and MMP-9 that play widespread and well-documented roles in tumor progression and metastasis. At the other end of the spectrum are probes that access tumors via their leaky vasculature (18). These probes are applicable to a wide range of tumors but are limited by contrast and nonspecificity.…”

Section: Discussionmentioning

confidence: 99%

Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival

Nguyen

Olson

Aguilera

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

445

310

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The completeness of tumor removal during surgery is dependent on the surgeon's ability to differentiate tumor from normal tissue using subjective criteria that are not easily quantifiable. A way to objectively assess tumor margins during surgery in patients would be of great value. We have developed a method to visualize tumors during surgery using activatable cell-penetrating peptides (ACPPs), in which the fluorescently labeled, polycationic cell-penetrating peptide (CPP) is coupled via a cleavable linker to a neutralizing peptide. Upon exposure to proteases characteristic of tumor tissue, the linker is cleaved, dissociating the inhibitory peptide and allowing the CPP to bind to and enter tumor cells. In mice, xenografts stably transfected with green fluorescent protein show colocalization with the Cy5-labeled ACPPs. In the same mouse models, Cy5-labeled free ACPPs and ACPPs conjugated to dendrimers (ACPPDs) delineate the margin between tumor and adjacent tissue, resulting in improved precision of tumor resection. Surgery guided by ACPPD resulted in fewer residual cancer cells left in the animal after surgery as measured by Alu PCR. A single injection of ACPPD dually labeled with Cy5 and gadolinium chelates enabled preoperative wholebody tumor detection by MRI, intraoperative guidance by real-time fluorescence, intraoperative histological analysis of margin status by fluorescence, and postoperative MRI tumor quantification. Animals whose tumors were resected with ACPPD guidance had better long-term tumor-free survival and overall survival than animals whose tumors were resected with traditional bright-field illumination only.intraoperative fluorescence imaging | molecular navigation | long-term survival | molecular imaging | surgical margin

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“…Fluorescence imaging of GBM involves labeling with°uorescing molecules such as°uores-cein, protoporphyrin IX or 5-aminolevulinic acid (5-ALA) which is promising to reveal brain tumor margins, yet su®ers from several restrictions. 2,17,18 First, only $ 80% of the cancer cells absorbed the°u orescing molecules. 2 Second, the nonspeci¯c labeling of dyes does not allow for tumor typing.…”

Section: Current Technologiesmentioning

confidence: 99%

Stimulated Raman scattering microscopy for rapid brain tumor histology

Yang

Chen

2017

J. Innov. Opt. Health Sci.

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Rapid histology of brain tissues with su±cient diagnostic information has the great potential to aid neurosurgeons during operations. Stimulated Raman Scattering (SRS) microscopy is an emerging label-free imaging technique, with the intrinsic chemical resolutions to delineate brain tumors from normal tissues without the need of time-consuming tissue processing. Growing number of studies have shown SRS as a \virtual histology" tool for rapid diagnosis of various types of brain tumors. In this review, we focus on the basic principles and current developments of SRS microscopy, as well as its applications for brain tumor imaging.

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Intraoperative Fluorescence Staining of Malignant Brain Tumors Using 5-Aminofluorescein-Labeled Albumin

Abstract: Tumor fluorescence using AFL-HSA made fluorescence-guided brain tumor resection possible, demonstrating that albumin is a suitable carrier system for selective targeting of aminofluorescein into malignant gliomas.

Cited by 53 publications

References 35 publications

Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival

Stimulated Raman scattering microscopy for rapid brain tumor histology

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