Fluorescence real-time kinetics of protoporphyrin IX after 5-ALA administration in low-grade glioma
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OBJECTIVE: 5-Aminolevulinic acid (5-ALA) induces fluorescence in high-grade glioma (HGG), which is used for resection. However, the value of 5-ALA-induced fluorescence in low-grade glioma (LGG) is unclear. Time dependency and time kinetics have not yet been investigated. The purpose of this study was to investigate real-time kinetics of protoporphyrin IX (PpIX) in LGG based on hyperspectral fluorescence-based measurements and identify factors that predict fluorescence. METHODS: Patients with grade II gliomas and imaging from which HGGs could not be completely ruled out received 5-ALA at 20 mg/kg body weight 4 hours prior to surgery. Fluorescence intensity (FI) and PpIX concentration (CPpIX) were measured in tumor tissue utilizing a hyperspectral camera. Apparent diffusion coefficient (ADC)-based tumor cell density, Ki-67/MIB-1 index, chromosomal 1p/19q codeletion, and 18F-fluoroethyl-l-tyrosine (18F-FET) PET values and their role for predicting fluorescence were evaluated. RESULTS: Eighty-one biopsies from 25 patients were included. Tissues with fluorescence demonstrated FI and CPpIX maxima between 7 and 8 hours after administration. When visible fluorescence was observed, peaks of FI and CPpIX were observed within this 7- to 8-hour time frame, regardless of any MRI gadolinium contrast enhancement. Gadolinium enhancement (p = 0.008), Ki-67/MIB-1 index (p < 0.001), 18F-FET PET uptake ratio (p = 0.004), and ADC-based tumor cellularity (p = 0.017) significantly differed between fluorescing and nonfluorescing tissue, but not 1p/19q codeletions. Logistic regression demonstrated that 18F-FET PET uptake and Ki-67/MIB-1 index were independently related to fluorescence. CONCLUSIONS: This study reports a fluorescence-based assessment of CPpIX in human LGG tissues related to 18F-FET PET uptake and Ki-67/MIB-1. As in HGGs, fluorescence in LGGs peaked between 7 and 8 hours after 5-ALA application, which has consequences for the timing of administration.
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Doubling the dose of ALA to 40 mg/kg or delaying the examination time to 7 and 8 h after ALA administration increases PpIX fluorescence in low-grade gliomas.
“There are studies showing that either doubling the dose of ALA to 40 mg/kg [55] or delaying the examination time to 7 and 8 h after ALA administration [53] increases the PpIX fluorescence in low-grade gliomas.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [53]
The association between positive PpIX fluorescence and gadolinium contrast enhancement highlights the importance of the blood-brain barrier in PpIX fluorescence positivity.
“Particularly, the association between positive PpIX fluorescence and gadolinium contrast enhancement highlights the importance of the blood-brain barrier (BBB) in PpIX fluorescence positivity.”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [53]
Comparison between fluorescing and non-fluorescing low-grade gliomas revealed significant differences in gadolinium enhancement, tumor cell proliferation, and 18F-FET PET uptake.
“A comparison between fluorescing and non-fluorescing low-grade gliomas revealed significant differences in gadolinium enhancement, tumor cell proliferation, and 18F-fluoroethyl-l-tyrosine (18F-FET) PET uptake, suggesting a distinction in tumor cell biology and tumor microenvironment [52,53].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [53]
PpIX fluorescence peaks at 7-8 h after ALA in patients with low-grade glioma or meningioma.
“PpIX fluorescence also peaks at 7–8 h after ALA in patients with low-grade glioma [53] or meningioma [71].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [53]
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- Authors
- Kaneko, S., Suero Molina, E., Sporns, P., Schipmann, S., Black, D., & Stummer, W.
- Affiliations
- Hokkaido University (JP)
- Department of Neurosurgery, University Hospital of Münster, Germany;
- University Hospital of Basel (CH)
- University Hospital Münster (DE)
- Carl Zeiss (Germany) (DE)
- Venue
- Journal of Neurosurgery
- Published
- 2022-01-01
- Volume
- 136
- Issue
- 1
- Pages
- 9-15
- ISSN
- 0022-3085 (ISSN-L)
- 1933-0693
- OpenAlex
- W3169851471
- Cited by
- 28
- References
- 32
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 12 · 2023: 7 · 2022: 4
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of neurosurgery (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- 5-aminolevulinic acid, protoporphyrin IX, low-grade glioma, fluorescence-guided surgery, fluorescence kinetics, hyperspectral fluorescence imaging, tumor cellularity, 1p/19q codeletion, gadolinium enhancement, glioma resection
- MeSH terms
- Adult, Aminolevulinic Acid, Brain Neoplasms, Chromosome Deletion, Female, Fluorescence, Glioma, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Protoporphyrins, Spectrometry, Fluorescence, Tyrosine, Photosensitizing Agents, Radiopharmaceuticals, Ki-67 Antigen, Positron-Emission Tomography
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