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Real-time in vivo kinetics of protoporphyrin IX after administration of 5-aminolevulinic acid in meningiomas and comparative analyses with glioblastomas

  • Original Article - Brain Tumors
  • Published:
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Abstract

Background

The usefulness of 5-aminolevulinic acid (5-ALA)–mediated fluorescence-guided surgery (FGS) in meningiomas is intensely discussed. However, data about kinetics of 5-ALA and protoporphyrin (Pp) IX in meningiomas are lacking.

Methods

As the first study so far, we performed longitudinal intraoperative real-time ex situ measurements of fluorescence intensity and PpIX concentrations during FGS of ten benign and two atypical meningiomas. Kinetics were subsequently compared with data from 229 glioblastomas.

Results

Spectroscopy revealed fluorescence (median 2945.65 a.u.) and PpIX accumulation (median 18.31 μg/ml) in all 43 analyzed samples. Fluorescence intensity (2961.50 a.u. vs 118.41 a.u.; p < .001) and PpIX concentrations (18.72 μg/ml vs .98 μg/ml; p < .001) were higher in samples with (N = 30) than without (N = 2) visible intraoperative tumor fluorescence. ROC curve analyses revealed a PpIX cut-off concentration of 3.85 μg/ml (AUC = .992, p = .005) and a quantitative fluorescence cut-off intensity of 286.73 a.u. (AUC = .983, p = .006) for intraoperative visible tumor fluorescence. Neither fluorescence intensity (p = .356) nor PpIX (p = .631) differed between atypical and benign meningiomas. Fluorescence and PpIX peaked 7–8 h following administration of 5-ALA. Meningiomas displayed a higher fluorescence intensity (p = .012) and PpIX concentration (p = .005) than glioblastomas 5–6 h after administration of 5-ALA. Although fluorescence was basically maintained, PpIX appeared to be cleared faster in meningiomas than in glioblastomas.

Conclusions

Kinetics of PpIX and fluorescence intensity differ between meningiomas and glioblastomas in the early phase after 5-ALA administration. Modification of the timing of drug administration might impact visibility of intraoperative fluorescence and helpfulness of FGS and should be investigated in future analyses.

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Author notes

  1. Sadahiro Kaneko and Benjamin Brokinkel contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, University Hospital Münster, Münster, Germany

    Sadahiro Kaneko, Benjamin Brokinkel, Eric Suero Molina, Nils Warneke, Markus Holling, Eva Christina Bunk & Walter Stummer

  2. Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Sadahiro Kaneko

  3. Institute of Neuropathology, University Hospital Münster, Münster, Germany

    Katharina Hess, Volker Senner & Werner Paulus

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  1. Sadahiro Kaneko
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Correspondence to Benjamin Brokinkel.

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Conflict of interest

Walter Setummer is a consultant of NX Development Corp., Lexington, KY, USA, and Photanamics GmbH & Co. KG, Pinneberg, Germany, and has been a speaker for Carl Zeiss AG, Oberkochen, Germany. The authors declare that they have no other conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Data collection and scientific use was approved by the local ethics committee (Münster 2018-061-f-S).

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Kaneko, S., Brokinkel, B., Suero Molina, E. et al. Real-time in vivo kinetics of protoporphyrin IX after administration of 5-aminolevulinic acid in meningiomas and comparative analyses with glioblastomas. Acta Neurochir 162, 2197–2202 (2020). https://doi.org/10.1007/s00701-020-04353-2

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  • DOI: https://doi.org/10.1007/s00701-020-04353-2

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