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Cited by 338Glioma Diagnosis and TreatmentOptical Imaging and Spectroscopy TechniquesPhotodynamic Therapy Research Studies

5-ALA and FDA Approval for Glioma Surgery

Open access
Hadjipanayis, Constantinos G., Stummer, Walter·2019·Journal of Neuro-Oncology
DOI 10.1007/s11060-019-03098-yPMC PMC6445645
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Abstract

The US Food and Drug Administration (FDA) approved 5-aminolevulinic acid (5-ALA; Gleolan®; photonamic GmbH and Co. KG) for use as an intraoperative optical imaging agent in patients with suspected high-grade gliomas (HGGs) in 2017. This was the first ever optical imaging agent approved as an adjunct for the visualization of malignant tissue during surgery for brain tumors. The approval occurred a decade after European approval and a multicenter, phase III randomized trial which confirmed that surgeons using 5-ALA fluorescence-guided surgery as a surgical adjunct could achieve more complete resections of tumors in HGG patients and better patient outcomes than with conventional microsurgery. Much of the delay in the US FDA approval of 5-ALA stemmed from its conceptualization as a therapeutic and not as an intraoperative imaging tool. We chronicle the challenges encountered during the US FDA approval process to highlight a new standard for approval of intraoperative optical imaging agents in brain tumors.

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Crossref · 10.1007/s11060-019-03098-y

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  • ALA-PpIX fluorescence-guided tumor resection has been approved for high-grade gliomas and bladder cancers where it shows better surgical outcomes than conventional white light surgery.

    “ALA-PpIX fluorescence-guided tumor resection has been approved for high-grade gliomas and bladder cancers where it shows better surgical outcomes than conventional white light surgery.”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [43]

    The 5-ALA History section (page unavailable) reports FDA approval for high-grade glioma surgery and more complete resections than with conventional white-light surgery. But the section “5-ALA as a Therapeutic or Intraoperative Imaging Agent” (page unavailable) says the bladder-cancer approval was for the 5-ALA derivative HAL as a detection agent, supported by better lesion detection—not approval for fluorescence-guided tumor resection or better surgical outcomes. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • FDA granted approval of ALA hydrochloride (Gleolan) in 2017 for intraoperative imaging in patients with high-grade gliomas following oral administration of 20 mg/kg about 3 h prior to anesthesia.

    “This landmark clinical trial together with additional clinical studies conducted afterward provided enough evidence for the FDA to grant the approval of ALA hydrochloride (Gleolan) in 2017 [43]. The approval allows the use of ALA as an intraoperative imaging probe to facilitate tumor resection in patients with high-grade gliomas (grade III or IV) following a standard oral administration of 20 mg/k”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [43]

    The Introduction states that the FDA approved oral Gleolan in June 2017 as an intraoperative optical imaging adjunct for patients with suspected grade III or IV gliomas. The FDA Orphan Drug Approval and New Drug Application section says the application drew on phase III trial results and additional diagnostic studies. Our copy does not establish the claimed 20 mg/kg dose or administration about three hours before anesthesia (searched: “20 mg/kg” and anesthesia timing). (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • ALA-mediated PpIX fluorescence in tumor tissues provides surgeons with a real-time guide for tumor diagnosis and margin assessment.

    “Because ALA-mediated PpIX fluorescence in tumor tissues is able to provide surgeons with a real-time guide for tumor diagnosis and margin assessment, ALA has been used as an intraoperative probe to facilitate tumor resection [43].”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [43]

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2 of the 59 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [21]Administration USFaD (1 16, 2006) FDA Workshop Brain Cancer End-Points

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Authors
Hadjipanayis, C. G., & Stummer, W.
Affiliations
University Hospital Münster (DE)
ORCID
Venue
Journal of Neuro-Oncology
Publisher
Springer Science and Business Media LLC
Published
2019-01-14
Volume
141
Issue
3
Pages
479-486
ISSN
  • 0167-594X (ISSN-L)
  • 1573-7373
DOI
10.1007/s11060-019-03098-y
PMC
PMC6445645
OpenAlex
W2910072132
Cited by
338
References
59
Citations by year
2026: 19 · 2025: 53 · 2024: 60 · 2023: 51 · 2022: 59 · 2021: 52 · 2020: 32 · 2019: 12
FWCI
4.75
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Journal of Neuro-Oncology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Merck
  • Novocure
  • Arbor Pharmaceuticals
  • National Cancer Institute (R01CA176659)
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
Keywords
5-aminolevulinic acid, fluorescence-guided surgery, high-grade glioma, FDA drug approval, brain tumor surgery, tumor resection completeness, regulatory challenges
MeSH terms
Aminolevulinic Acid, Brain Neoplasms, Fluorescent Dyes, Glioma, Humans, United States, United States Food and Drug Administration, Drug Approval, Surgery, Computer-Assisted, Optical Imaging

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