Deferoxamine may enhance 5-aminolevulinic acid-based fluorescence in glioma surgery

Abstract Background Gliomas are composed of multiple clones of tumor cells. This intratumor heterogeneity contributes to the ability of gliomas to resist treatment. It is vital that gliomas are fully characterized at a molecular level when a diagnosis is made to maximize treatment effectiveness. Methods We collected ultrasonic tissue fragments during glioma surgery. Large tissue fragments were separated in the operating theater and bathed continuously in oxygenated artificial cerebrospinal fluid to keep them alive. The ex vivo tissue fragments were transferred to a laboratory and incubated in 5-aminolevulinic acid (5-ALA). 5-ALA is metabolized to Protoporphyrin IX (PpIX), which accumulates in glioma cells and makes them fluorescent. The molecular and neuropathological features of the PpIX fluorescent ultrasonic tissue fragments were studied. Results We show that PpIX fluorescence can rapidly identify tissue fragments infiltrated by glioma in the laboratory. Ultrasonic tissue fragments from the tumor core provided molecular and neuropathological information about the glioma that was comparable to the surgical biopsy. We characterized the heterogeneity within individual gliomas by studying ultrasonic tissue fragments from different parts of the tumor. We found that gliomas exhibit a power relationship between cellular proliferation and tumor infiltration. Tissue fragments that deviate from this relationship may contain foci of more malignant glioma. The methylation status of the O6-methylguanine DNA methyltransferase gene promoter varied within each glioma. Conclusions Ex vivo ultrasonic tissue fragments can be rapidly screened for glioma infiltration. They offer a viable platform to characterize heterogeneity within individual gliomas, thereby enhancing their diagnosis and treatment.

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Use of 5-aminolevulinic acid in fluorescence-guided resection of meningioma with high risk of recurrence

Journal of Neurosurgery ◽

10.3171/jns.2007.106.6.1070 ◽

2007 ◽

Vol 106 (6) ◽

pp. 1070-1074 ◽

Cited By ~ 68

Author(s):

Yoshinaga Kajimoto ◽

Toshihiko Kuroiwa ◽

Shin-Ichi Miyatake ◽

Tsugumichi Ichioka ◽

Minoru Miyashita ◽

...

Keyword(s):

High Risk ◽

Tumor Tissue ◽

Aminolevulinic Acid ◽

Superior Sagittal Sinus ◽

Residual Tumor ◽

Strong Fluorescence ◽

Glioma Surgery ◽

Risk Of Recurrence ◽

Sagittal Sinus ◽

Atypical Meningiomas

✓It has been established that fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is useful in glioma surgery. The authors report on a 65-year-old woman who had a huge atypical left-hemisphere meningioma, which extended into the skull and to the superior sagittal sinus and demonstrated fluorescence in response to administration of 5-ALA. After the tumor was removed, the operative field was observed under the fluorescent mode of a fluorescence surgical microscopy system. Several minute areas of residual tumor tissue were visualized as strong fluorescence behind the vein and sinus, in a part of the hypertrophic dura, and along the edge of the skull. These remnants were completely removed. The authors concluded that fluorescence-guided resection using 5-ALA is useful in cases of atypical meningiomas with a high risk of recurrence.

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Efficacy of 5-aminolevulinic acid-induced fluorescence detection in malignant glioma surgery

International Congress Series ◽

10.1016/j.ics.2004.03.324 ◽

2004 ◽

Vol 1268 ◽

pp. 1290

Author(s):

Takashi Maruyama ◽

Yoshihiro Muragaki ◽

Masahiko Tanaka ◽

Hiroshi Iseki ◽

Ichiro Sakuma ◽

...

Keyword(s):

Malignant Glioma ◽

Fluorescence Detection ◽

Aminolevulinic Acid ◽

Glioma Surgery

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FLGS-01. Development of novel topical fluorescent probe for intraoperative rapid detection of glioma

Neuro-Oncology ◽

10.1093/neuonc/noab196.905 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi225-vi226

Author(s):

Shota Tanaka ◽

Yosuke Kitagawa ◽

Mako Kamiya ◽

Takenori Shimizu ◽

Yasuteru Urano ◽

...

Keyword(s):

Malignant Glioma ◽

Fluorescent Probe ◽

Rapid Detection ◽

Aminolevulinic Acid ◽

Characteristic Curve ◽

Screening Method ◽

Tumor Resection ◽

Phase Iii ◽

Glioma Surgery ◽

Two Dimensional Gel Electrophoresis

Abstract PURPOSE Fluorescence imaging is an important surgical adjunct in malignant glioma surgery. 5-aminolevulinic acid (5-ALA) has been proven effective for radical tumor resection and extended progression-free survival in a phase III randomized trial and therefore integrated into surgery for malignant glioma. Importantly, however, some limitations still exist in its use, which include false positivity and false negativity as well as inability of re-administration. In this study, we aimed to develop a novel, spray-type fluorescent probe using hydroxymethyl rhodamine green (HMRG) as a fluorescent scaffold. METHODS We have previously established a fluorescent probe library comprised of more than 320 kinds of HMRG probes. They have HMRG as a fluorescent scaffold with various types of dipeptides attached to it. Primary probe screening was performed using the homogenized tumor samples from patients with glioblastoma operated at our institution. Secondary screening followed using the selected probes and fresh tumor samples obtained from patients with glioblastoma operated from 2016 until 2018. Diced electrophoresis gel (DEG) assay, two-dimensional gel electrophoresis followed by a multi-well plate-based fluorometric assay, was performed to identify responsible enzymes for the selected probe. Further experiments with inhibitors, real-time PCR, immunohistochemistry, and western blotting were performed for confirmation. RESULTS Proline-arginine-HMRG (PR-HMRG) was selected as a candidate probe based upon the above two-step screenings. It achieved 79.4% accuracy in receiver operating characteristic curve analysis. Calpain-1 was found to be responsible to cleave PR-HMRG probe by DEG-proteome analysis. Calpain-1 protein was highly expressed in tumor tissues which reacted to PR-HMRG probe. CONCLUSIONS Our innovative screening method was able to find PR-HMRG as a novel fluorescent probe effective for rapid detection of glioblastoma. A preclinical study is planned to assess the efficacy and safety of the selected probe.

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FLUORESCENCE OF NON-NEOPLASTIC, MAGNETIC RESONANCE IMAGING-ENHANCING TISSUE BY 5-AMINOLEVULINIC ACID

Neurosurgery ◽

10.1227/01.neu.0000303209.38360.e6 ◽

2007 ◽

Vol 61 (5) ◽

pp. E1101-E1104 ◽

Cited By ~ 35

Author(s):

Shin-Ichi Miyatake ◽

Toshihiko Kuroiwa ◽

Yoshinaga Kajimoto ◽

Minoru Miyashita ◽

Hidekazu Tanaka ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Demyelinating Disease ◽

Aminolevulinic Acid ◽

Radiation Necrosis ◽

Malignant Tumors ◽

Central Nervous System Disease ◽

Resonance Imaging ◽

Glioma Surgery ◽

System Disease

Abstract OBJECTIVE It has been established that fluorescence-guided resection using 5-aminolevulinic acid is useful in glioma surgery. In this study, we describe three cases in which even perinecrotic tissue could be recognized as fluorescence positive. METHODS Three cases of central nervous system disease, showing gadolinium enhancement on magnetic resonance imaging scans, were operated on with the aid of fluorescence derived from 5-aminolevulinic acid. Two of these were diagnosed as radiation necrosis and the other as a neurodegenerative demyelinating disease. RESULTS In all cases, at least some parts of the gadolinium-enhanced area could be labeled as fluorescence positive, whereas centers of necrotic tissue were negative for fluorescence. Histologically, cell infiltration was marked in each case that showed fluorescence activity. CONCLUSION Both malignant tumors and the perinecrotic area in radiation necrosis or neurodegenerative disease can be labeled as fluorescence positive using 5-aminolevulinic acid.

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To what extent will 5-aminolevulinic acid change the face of malignant glioma surgery?

CNS Oncology ◽

10.2217/cns.15.10 ◽

2015 ◽

Vol 4 (4) ◽

pp. 265-272 ◽

Cited By ~ 6

Author(s):

Ricardo Díez Valle ◽

Sonia Tejada Solis

Keyword(s):

Malignant Glioma ◽

Aminolevulinic Acid ◽

Glioma Surgery ◽

The Face

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Reliability of Intraoperative Monitoring in Patients with a Preexisting Motor Deficit: Case Report and Literature Review

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/s-0039-1698396 ◽

2020 ◽

Author(s):

Ravindran Visagan ◽

José Pedro Lavrador ◽

Shami Acharya ◽

Noemia Pereira ◽

Istvan Bodi ◽

...

Keyword(s):

Intraoperative Monitoring ◽

Aminolevulinic Acid ◽

Clinical Course ◽

Motor Evoked Potentials ◽

Motor Deficit ◽

Glioma Surgery ◽

Cortical Motor ◽

Full Power ◽

Safe Zones

Abstract Background The use of intraoperative monitoring (IOM) in glioma surgery is a widely adopted and clinically validated adjunct to define safe zones of resection for the neurosurgeon. However, the role of IOM in cases of a significant preexisting motor deficit is questionable. Case Description We describe a case of a 25-year-old with a recurrent presentation of a left paracentral glioblastoma, admitted with intratumoral hemorrhage and subsequent acute severe right-sided weakness. The patient underwent a redo left parietal craniotomy and 5-aminolevulinic acid–guided resection with IOM. The severity of the weakness was not reflected by the pre- and intraoperative cortical motor evoked potentials (MEPs) that were reassuring. The patient's hemiparesis recovered to full power postoperatively. Conclusions Preoperative weakness is traditionally accepted as a relative contraindication to IOM and therefore its usefulness is questioned in this context. Our case challenges this assumption. We present the clinical course, review the cranial and spinal literature including the reliability of IOM in cases of preoperative motor deficit, and discuss the need for tailor-made IOM strategies.

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Gross Total Resection Rates in Contemporary Glioblastoma Surgery

Neurosurgery ◽

10.1227/neu.0b013e31826d1e6b ◽

2012 ◽

Vol 71 (5) ◽

pp. 927-936 ◽

Cited By ~ 120

Author(s):

Philippe Schucht ◽

Jürgen Beck ◽

Janine Abu-Isa ◽

Lukas Andereggen ◽

Michael Murek ◽

...

Keyword(s):

Aminolevulinic Acid ◽

Complete Resection ◽

High Rate ◽

Gross Total Resection ◽

Neurological Deficits ◽

Total Resection ◽

Glioma Surgery ◽

Intraoperative Mapping ◽

Number Of Patients ◽

The Impact

Abstract BACKGROUND: Complete resection of contrast-enhancing tumor has been recognized as an important prognostic factor in patients with glioblastoma and is a primary goal of surgery. Various intraoperative technologies have recently been introduced to improve glioma surgery. OBJECTIVE: To evaluate the impact of using 5-aminolevulinic acid and intraoperative mapping and monitoring on the rate of complete resection of enhancing tumor (CRET), gross total resection (GTR), and new neurological deficits as part of an institutional protocol. METHODS: One hundred three consecutive patients underwent resection of glioblastoma from August 2008 to November 2010. Eligibility for CRET was based on the initial magnetic resonance imaging assessed by 2 reviewers. The primary end point was the number of patients with CRET and GTR. Secondary end points were volume of residual contrast-enhancing tissue and new postoperative neurological deficits. RESULTS: Fifty-three patients were eligible for GTR/CRET (n = 43 newly diagnosed glioblastoma, n = 10 recurrent); 13 additional patients received surgery for GTR/CRET-ineligible glioblastoma. GTR was achieved in 96% of patients (n = 51, no residual enhancement > 0.175 cm3); CRET was achieved in 89% (n = 47, no residual enhancement). Postoperatively, 2 patients experienced worsening of preoperative hemianopia, 1 patient had a new mild hemiparesis, and another patient sustained sensory deficits. CONCLUSION: Using 5-aminolevulinic acid imaging and intraoperative mapping/monitoring together leads to a high rate of CRET and an increased rate of GTR compared with the literature without increasing the rate of permanent morbidity. The combination of safety and resection-enhancing intraoperative technologies was likely to be the major drivers for this high rate of CRET/GTR.

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