Interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor

Interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor

Photodynamic therapy (PDT) remains a promising therapeutic approach that requires further study in high grade gliomas. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies 1). 2).

PDT might be feasible for eliminating brain tumor cells in malignant pediatric brain tumors 3)


Computer simulation of the photophysical process in ALA-iPDT can offer a quantitative tool for understanding treatment outcomes, which depend on various variables related to clinical treatment conditions. Izumoto et al. proposed a clinical simulation method of ALA-iPDT for malignant brain tumors using a singlet oxygen (O12) model and O12 threshold to induce cell death. In this method, the amount of O12 generated is calculated using a photosensitizer photobleaching coefficient and O12 quantum yield, which have been measured in several previous studies. Results of the simulation using clinical magnetic resonance imaging data show the need to specify the insertion positions of cylindrical light diffusers and the level of light fluence. Detailed analysis with a numerical brain tumor model demonstrates that ALA-iPDT treatment outcomes depend on combinations of photobleaching and threshold values. These results indicate that individual medical procedures, including pretreatment planning and treatment monitoring, will greatly benefit from simulation of ALA-iPDT outcomes 4).


Glioma stem cells (GSLCs) expressed higher mRNA levels of protoporphyrin IX (PpIX) biosynthesis enzymes and its transporters PEPT1/2 and ABCB6, when compared to the parental A172 glioma cells. Consistently, flow cytometry analysis revealed that upon incubation with ALA, GSLCs accumulate a higher level of PpIX. Finally, Fujishiro et al., from the Department of Neurosurgery, Osaka Medical College, Takatsuki, Japan showed that GSLCs were more sensitive to 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) than the original A172 cells, and confirmed that all patient-derived glioma sphere lines also showed significantly increased sensitivity to ALA-PDT if cultivated under the pro-stem cell condition. This data indicate that ALA-PDT has potential as a novel clinically useful treatment that might eliminate GBM stem cells that are highly resistant to the current chemo- and radio-therapy 5).

References

1)

Mahmoudi K, Garvey KL, Bouras A, Cramer G, Stepp H, Jesu Raj JG, Bozec D, Busch TM, Hadjipanayis CG. 5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas. J Neurooncol. 2019 Feb;141(3):595-607. doi: 10.1007/s11060-019-03103-4. Epub 2019 Jan 18. Review. PubMed PMID: 30659522; PubMed Central PMCID: PMC6538286.
2)

Beck TJ, Kreth FW, Beyer W, Mehrkens JH, Obermeier A, Stepp H, Stummer W, Baumgartner R. Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5-aminolevulinic acid induced protoporphyrin IX. Lasers Surg Med. 2007 Jun;39(5):386-93. PubMed PMID: 17565715.
3)

Schwake M, Nemes A, Dondrop J, Schroeteler J, Schipmann S, Senner V, Stummer W, Ewelt C. In-Vitro Use of 5-ALA for Photodynamic Therapy in Pediatric Brain Tumors. Neurosurgery. 2018 Dec 1;83(6):1328-1337. doi: 10.1093/neuros/nyy054. PubMed PMID: 29538709.
4)

Izumoto A, Nishimura T, Hazama H, Ikeda N, Kajimoto Y, Awazu K. Singlet oxygen model evaluation of interstitial photodynamic therapy with 5-aminolevulinic acid for malignant brain tumor. J Biomed Opt. 2019 Dec;25(6):1-13. doi: 10.1117/1.JBO.25.6.063803. PubMed PMID: 31838789.
5)

Fujishiro T, Nonoguchi N, Pavliukov M, Ohmura N, Park Y, Kajimoto Y, Ishikawa T, Nakano I, Kuroiwa T. 5-aminolevulinic acid-mediated photodynamic therapy can target human glioma stem-like cells refractory to antineoplastic agents. Photodiagnosis Photodyn Ther. 2018 Jul 7. pii: S1572-1000(18)30185-6. doi: 10.1016/j.pdpdt.2018.07.004. [Epub ahead of print] PubMed PMID: 29990642.

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