Next Article in Journal
Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis
Previous Article in Journal
Dubious Claims about Simplicity and Likelihood: Comment on Pinna and Conti (2019)
Previous Article in Special Issue
Intersection of Brain Development and Paediatric Diffuse Midline Gliomas: Potential Role of Microenvironment in Tumour Growth
Open AccessPerspective

A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen

1
IIAIGC Study Center, 148 College Street, suite 202, Burlington, VT 05401, USA
2
Southern Illinois University School of Medicine, Division of Neurosurgery, PO Box 19638, Springfield, IL 62794, USA
3
Neuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, viale Pieraccini, 50139 24 Florence, Italy
4
Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA
5
Department of Neurosurgery, Ulm University Hospital, Albert-Einstein-Allee 23, D-89081 Ulm, Germany
6
Clemenceau Medical Centre, Department of Hematology-Oncology, Lebanese American University, Byblos Lebanon, City Centre Bldg. Suite 3A, Avenue Nouvelle, P.O. Box 1076, Jounieh, Lebanon
*
Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(1), 51; https://doi.org/10.3390/brainsci10010051
Received: 2 December 2019 / Revised: 14 January 2020 / Accepted: 16 January 2020 / Published: 17 January 2020
(This article belongs to the Special Issue Tumour Microenvironment in Paediatric Brain Tumour)
Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a planned study of adding 5-aminolevulinic acid (5-ALA) to the current irradiation of DIPG or DMG: the 5aai regimen. In a series of recent papers, oral 5-ALA was shown to enhance standard therapeutic ionizing irradiation. 5-ALA is currently used in glioblastoma surgery to enable demarcation of overt tumor margins by virtue of selective uptake of 5-ALA by neoplastic cells and selective conversion to protoporphyrin IX (PpIX), which fluoresces after excitation by 410 nm (blue) light. 5-ALA is also useful in treating glioblastomas by virtue of PpIX’s transfer of energy to O2 molecules, producing a singlet oxygen that in turn oxidizes intracellular DNA, lipids, and proteins, resulting in selective malignant cell cytotoxicity. This is called photodynamic treatment (PDT). Shallow penetration of light required for PpIX excitation and resultant energy transfer to O2 and cytotoxicity results in the inaccessibility of central structures like the pons or thalamus to sufficient light. The recent demonstration that keV and MeV photons can also excite PpIX and generate singlet O2 allows for reconsideration of 5-ALA PDT for treating DMG and DIPG. 5-ALA has an eminently benign side effect profile in adults and children. A pilot study in DIPG/DMG of slow uptitration of 5-ALA prior to each standard irradiation session—the 5aai regimen—is warranted. View Full-Text
Keywords: 5-aminolevulinic acid; diffuse intrinsic pontine glioma; diffuse midline gliomas; fluorescence; glioblastoma; irradiation; photodynamic; prognosis; protoporphyrin IX; reactive oxygen species 5-aminolevulinic acid; diffuse intrinsic pontine glioma; diffuse midline gliomas; fluorescence; glioblastoma; irradiation; photodynamic; prognosis; protoporphyrin IX; reactive oxygen species
MDPI and ACS Style

Kast, R.E.; Michael, A.P.; Sardi, I.; Burns, T.C.; Heiland, T.; Karpel-Massler, G.; Kamar, F.G.; Halatsch, M.-E. A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen. Brain Sci. 2020, 10, 51.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop