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

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

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

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.

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

CNS Oncology ◽  
2015 ◽  
Vol 4 (4) ◽  
pp. 265-272 ◽  
Author(s):  
Ricardo Díez Valle ◽  
Sonia Tejada Solis
Keyword(s):  
Malignant Glioma ◽  
Aminolevulinic Acid ◽  
Glioma Surgery ◽  
The Face

Observational, retrospective study of the effectiveness of 5-aminolevulinic acid in malignant glioma surgery in Spain (The VISIONA study)

2014 ◽  
Vol 29 (3) ◽  
pp. 131-138 ◽  
Author(s):  
R. Díez Valle ◽  
J. Slof ◽  
J. Galván ◽  
C. Arza ◽  
C. Romariz ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Malignant Glioma ◽  
Aminolevulinic Acid ◽  
Glioma Surgery

SURG-10. DEVELOPMENT OF NOVEL TOPICAL FLUORESCENT PROBE FOR INTRAOPERATIVE RAPID DETECTION OF GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi197-vi197
Author(s):  
Shota Tanaka ◽  
Yosuke Kitagawa ◽  
Mako Kamiya ◽  
Yugo Kuriki ◽  
Kyoko Yamamoto ◽  
...  
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 expressed at significantly higher level in tumors that were fluoresced by PR-HMRG than in those that were not. 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.

Endoscopic-Assisted Visualization of 5-Aminolevulinic Acid–Induced Fluorescence in Malignant Glioma Surgery: A Technical Note

2014 ◽  
Vol 82 (1-2) ◽  
pp. e277-e279 ◽  
Author(s):  
Marion Rapp ◽  
Marcel Kamp ◽  
Hans-Jakob Steiger ◽  
Michael Sabel
Keyword(s):  
Malignant Glioma ◽  
Aminolevulinic Acid ◽  
Technical Note ◽  
Glioma Surgery

Association of 5-aminolevulinic acid with intraoperative hypotension in malignant glioma surgery

2021 ◽  
pp. 102657
Author(s):  
Shumpei Morisawa ◽  
Kohei Jobu ◽  
Tomoaki Ishida ◽  
Kei Kawada ◽  
Hitoshi Fukuda ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Aminolevulinic Acid ◽  
Glioma Surgery ◽  
Intraoperative Hypotension

Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study

2011 ◽  
Vol 114 (3) ◽  
pp. 613-623 ◽  
Author(s):  
Walter Stummer ◽  
Jörg-Christian Tonn ◽  
Hubertus Maximilian Mehdorn ◽  
Ulf Nestler ◽  
Kea Franz ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Aminolevulinic Acid ◽  
Malignant Gliomas ◽  
Neurological Function ◽  
Phase Iii ◽  
Neurological Deficits ◽  
Secondary Outcome ◽  
Karnofsky Performance Scale ◽  
Glioma Surgery ◽  
Repeat Surgery

Object Accumulating data suggest more aggressive surgery in patients with malignant glioma to improve outcome. However, extended surgery may increase morbidity. The randomized Phase III 5-aminolevulinic acid (ALA) study investigated 5-ALA–induced fluorescence as a tool for improving resections. An interim analysis demonstrated more frequent complete resections with longer progression-free survival (PFS). However, marginal differences were found regarding neurological deterioration and the frequency of additional therapies. Presently, the authors focus on the latter aspects in the final study population, and attempt to determine how safety might be affected by cytoreductive surgery. Methods Patients with malignant gliomas were randomized for fluorescence-guided (ALA group) or conventional white light (WL) (WL group) microsurgery. The final intent-to-treat population consisted of 176 patients in the ALA and 173 in the WL group. Primary efficacy variables were contrast-enhancing tumor on early MR imaging and 6-month PFS. Among secondary outcome measures, the National Institutes of Health Stroke Scale (NIH-SS) score and the Karnofsky Performance Scale (KPS) score were used for assessing neurological function. Results More frequent complete resections and improved PFS were confirmed, with higher median residual tumor volumes in the WL group (0.5 vs 0 cm3, p = 0.001). Patients in the ALA group had more frequent deterioration on the NIH-SS at 48 hours. Patients at risk were those with deficits unresponsive to steroids. No differences were found in the KPS score. Regarding outcome, a combined end point of risks and neurological deficits was attempted, which demonstrated results in patients in the ALA group to be superior to those in participants in the WL group. Interestingly, the cumulative incidence of repeat surgery was significantly reduced in ALA patients. When stratified by completeness of resection, patients with incomplete resections were quicker to deteriorate neurologically (p = 0.0036). Conclusions Extended resections performed using a tool such as 5-ALA–derived tumor fluorescence, carries the risk of temporary impairment of neurological function. However, risks are higher in patients with deficits unresponsive to steroids.

Following the light in glioma surgery: a comparison of sodium fluorescein and 5-aminolevulinic acid as surgical adjuncts in glioma resection

2020 ◽  
Vol 63 (6) ◽  
Author(s):  
Jorge Navarro-Bonnet ◽  
Paola Suarez-Meade ◽  
Desmond A. Brown ◽  
Kaisorn L. Chaichana ◽  
Alfredo Quinones-Hinojosa
Keyword(s):  
Aminolevulinic Acid ◽  
Sodium Fluorescein ◽  
Glioma Surgery ◽  
Glioma Resection
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