A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen
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...
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| Format: | Article |
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MDPI AG
2020-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/10/1/51 |
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| author | Richard E. Kast Alex P. Michael Iacopo Sardi Terry C. Burns Tim Heiland Georg Karpel-Massler Francois G. Kamar Marc-Eric Halatsch |
| author_facet | Richard E. Kast Alex P. Michael Iacopo Sardi Terry C. Burns Tim Heiland Georg Karpel-Massler Francois G. Kamar Marc-Eric Halatsch |
| author_sort | Richard E. Kast |
| collection | DOAJ |
| description | 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 O<sub>2</sub> 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 O<sub>2</sub> 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 O<sub>2</sub> 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. |
| first_indexed | 2024-12-19T05:40:46Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-12-19T05:40:46Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-89f2a527688f4ef69437527885f1a9ca2022-12-21T20:34:01ZengMDPI AGBrain Sciences2076-34252020-01-011015110.3390/brainsci10010051brainsci10010051A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai RegimenRichard E. Kast0Alex P. Michael1Iacopo Sardi2Terry C. Burns3Tim Heiland4Georg Karpel-Massler5Francois G. Kamar6Marc-Eric Halatsch7IIAIGC Study Center, 148 College Street, suite 202, Burlington, VT 05401, USASouthern Illinois University School of Medicine, Division of Neurosurgery, PO Box 19638, Springfield, IL 62794, USANeuro-Oncology Unit, Department of Pediatric Oncology, Meyer Children’s Hospital, viale Pieraccini, 50139 24 Florence, ItalyDepartment of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USADepartment of Neurosurgery, Ulm University Hospital, Albert-Einstein-Allee 23, D-89081 Ulm, GermanyDepartment of Neurosurgery, Ulm University Hospital, Albert-Einstein-Allee 23, D-89081 Ulm, GermanyClemenceau Medical Centre, Department of Hematology-Oncology, Lebanese American University, Byblos Lebanon, City Centre Bldg. Suite 3A, Avenue Nouvelle, P.O. Box 1076, Jounieh, LebanonDepartment of Neurosurgery, Ulm University Hospital, Albert-Einstein-Allee 23, D-89081 Ulm, GermanyPrognosis 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 O<sub>2</sub> 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 O<sub>2</sub> 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 O<sub>2</sub> 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.https://www.mdpi.com/2076-3425/10/1/515-aminolevulinic aciddiffuse intrinsic pontine gliomadiffuse midline gliomasfluorescenceglioblastomairradiationphotodynamicprognosisprotoporphyrin ixreactive oxygen species |
| spellingShingle | Richard E. Kast Alex P. Michael Iacopo Sardi Terry C. Burns Tim Heiland Georg Karpel-Massler Francois G. Kamar Marc-Eric Halatsch A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen Brain Sciences 5-aminolevulinic acid diffuse intrinsic pontine glioma diffuse midline gliomas fluorescence glioblastoma irradiation photodynamic prognosis protoporphyrin ix reactive oxygen species |
| title | A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen |
| title_full | A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen |
| title_fullStr | A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen |
| title_full_unstemmed | A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen |
| title_short | A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen |
| title_sort | new treatment opportunity for dipg and diffuse midline gliomas 5 ala augmented irradiation the 5aai regimen |
| topic | 5-aminolevulinic acid diffuse intrinsic pontine glioma diffuse midline gliomas fluorescence glioblastoma irradiation photodynamic prognosis protoporphyrin ix reactive oxygen species |
| url | https://www.mdpi.com/2076-3425/10/1/51 |
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