5-aminolevulinic acid-induced accumulation of protoporphyrin IX in rat brain tissue
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Keywords

photodynamic therapy
5-aminolevulinic acid
Alasens
brain
glioma C6

How to Cite

Kokorina, A., Rafaelyan, A., Chemodakova, K., Pak, N., Aleksandrov, V., Svistov, D. ., Martynov, B. ., & Vasileva, N. (2021). 5-aminolevulinic acid-induced accumulation of protoporphyrin IX in rat brain tissue. Voprosy Onkologii, 67(6), 849–854. https://doi.org/10.37469/0507-3758-2021-67-6-849-854

Abstract

The aim of the study was to compare the level of accumulation of protoporphyrin IX (ППIX) in the brain of rats in normal conditions and in experimental C6 glioma.

Materials and methods. In an experiment on 15 rats, one group of animals (n=5) was intracranially implanted with rat glioma of the C6 line. 14 days after tumor implantation, the animals were injected into the lateral vein of the tail with a photosensitizer — a preparation of 5-aminolevulinic acid (5-ALA) Alasens at a dose of 100 mg / kg. Another group consisted of 5 intact rats, which were also injected with Alasens. The rats were euthanized 4–5 hours after the injection of the photosensitizer, and fluorescent metabolic navigation was performed with illumination of the brain with light with wavelengths of 417 and 435 nm. For objectification, fluorescence biospectroscopy was performed. Similar manipulations were performed with animals of another group (n=5) — intact rats that did not receive Alasens.

Results. In contrast to humans, in rats, the 5-ALA metabolite — PPIX accumulates in healthy brain tissue, while the fluorescence intensity does not differ from that visualized in the tumor area. It was also noted that the light of the blue spectrum promotes weak fluorescence of the white matter of the rat brain in the absence of exogenous 5-ALA, which can potentially be explained by the activation of endogenous PPIX or other fluorophores.

Conclusion. After the administration of Alasens (5-ALA preparation), the accumulation of PPIX by the rat brain tissue occurs not only by malignant cells, but also by normal brain tissue without signs of malignancy or other pathological changes. A more thorough study of this phenomenon is required, since significant differences in the metabolism of 5-ALA in humans and laboratory animals will call into question the correctness of translation of experimental results into clinical practice.

https://doi.org/10.37469/0507-3758-2021-67-6-849-854
pdf (Русский)

References

Рафаелян А.А., Алексеев Д.Е., Мартынов Б.В. и др. Стереотаксическая фотодинамическая терапия в лечении рецидива глиобластомы. Случай из практики и обзор литературы // Журнал «Вопросы нейрохирургии» им. Н.Н. Бурденко. 2020;84(5):81–88 [Rafaelyan AA, Alekseev DE, Martynov BV et al. Stereotactic photodynamic therapy in the treatment of glioblastoma recurrence. Case study and literature review // Zhurnal Voprosy Neirokhirurgii Imeni N.N. Burdenko. 2020;84(5):81–88 (In Russ.)]. doi.org/10.17116/neiro20208405181

Артемкин Э.Н., Крюков Е.В., Соколов А.А. и др. Первый опыт внутрипротоковой фотодинамической терапии опухоли Клацкина с использованием технологии SpyGlass™ DS в России // Хирург. 2020;3–4:58–71 [Artemkin EN, Kryukov EV, Sokolov AA et al. The first experience of intraductal photodynamic therapy of Klatskin's tumor using SpyGlass ™ DS technology in Russia // Surgeon. 2020;3–4:58–71 (In Russ.)]. doi:10.33920/med-15-2002-06

Stepp H, Stummer W. 5-ALA in the management of malignant glioma // Lasers Surg Med. 2018;50(5):399–419. doi:10.1002/lsm.22933

Mahmoudi K, Garvey KL, Bouras A et al. 5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas // J Neurooncol. 2019;141(3):595–607. doi:10.1007/s11060-019-03103-4

Горяйнов С.А., Потапов А.А., Пицхелаури Д.И. и др. Интраоперационная флуоресцентная диагностика и лазерная спектроскопия при повторных операциях по поводу глиом головного мозга // Журнал «Вопросы нейрохирургии» им. Н.Н. Бурденко. 2014;78(2):22–31 [Goryainov SA, Potapov AA, Pitskhelauri DI et al. Intraoperative fluorescence diagnostics and laser spectroscopy in repeated operations for cerebral gliomas // The journal «Questions of neurosurgery» named after N.N. Burdenko. 2014;78(2):22–31 (In Russ.)].

Кубасова И.Ю., Смирнова З.С., Ермакова К.В. и др. Флюоресцентная диагностика и фотодинамическая терапия злокачественных глиом у крыс // Российский онкологический журнал. 2013;2:14–18 [Kubasova IYu, Smirnova ZS, Ermakova KV et al. Fluorescence diagnosis and photodynamic therapy of malignant gliomas in rats // Russian Journal of Oncology. 2013;2:14–18 (In Russ.)].

Lilge L, Wilson BC. Photodynamic therapy of intracranial tissues: a preclinical comparative study of four different photosensitizers // J Clin Laser Med Surg. 1998;16(2):81–91. doi:10.1089/clm.1998.16.81

Фисенко Д.Е., Козар Я.В., Раджабов Р.М. и др. Опухолевая прогрессия глиобластомы C6 при измененном тиреоидном статусе // FORCIPE. 2019;9–14 [Fisenko DE, Kozar YaV, Radzhabov RM et al. Tumor progression of C6 glioblastoma with altered thyroid status // FORCIPE. 2019;9–14 (In Russ.)].

Cho SS, Sheikh S, Teng CW et al. Evaluation of diagnostic accuracy following the coadministration of delta-aminolevulinic acid and second window indocyanine green in rodent and human glioblastomas // Mol Imaging Biol. 2020;22(5):1266–1279. doi:10.1007/s11307-020-01504-w

Hebeda KM, Saarnak AE, Olivo M et al. 5-Aminolevulinic acid induced endogenous porphyrin fluorescence in 9L and C6 brain tumours and in the normal rat brain // Acta Neurochir (Wien). 1998;140(5):503–12;discussion 512–3. doi:10.1007/s007010050132

Hirschberg H, Spetalen S, Carper S et al. Minimally invasive photodynamic therapy (PDT) for ablation of experimental rat glioma // Minim Invasive Neurosurg. 2006;49(3):135–142. doi:10.1055/s-2006-932216

Потапов А.А., Гаврилов А.Г., Горяйнов С.А. и др. Интраоперационная флуоресцентная диагностика и лазерная спектроскопия в хирургии глиальных опухолей головного мозга // Журнал «Вопросы нейрохирургии» им. Н.Н. Бурденко. 2012;76(5):3–12 [Potapov AA, Gavrilov AG, Goryainov SA. And other Intraoperative fluorescence diagnostics and laser spectroscopy in surgery of glial brain tumors // The journal «Questions of neurosurgery» named after N.N. Burdenko. 2012;76(5):3–12 (In Russ.)].

Madsen SJ, Angell-Petersen E, Spetalen S et al. Photodynamic therapy of newly implanted glioma cells in the rat brain // Lasers Surg Med. 2006;38(5):540–8. doi:10.1002/lsm.20274

Madsen SJ, Kharkhuu K, Hirschberg H. Utility of the F98 rat glioma model for photodynamic therapy // J Environ Pathol Toxicol Oncol. 2007;26(2):149–55. doi:10.1615/jenvironpatholtoxicoloncol.v26.i2.100

Mathews MS, Chighvinadze D, Gach HM et al. Cerebral edema following photodynamic therapy using endogenous and exogenous photosensitizers in normal brain // Lasers Surg Med. 2011;43(9):892–900. doi:10.1002/lsm.21135

Kimura S, Kuroiwa T, Ikeda N et al. Assessment of safety of 5-aminolevulinic acid-mediated photodynamic therapy in rat brain // Photodiagnosis Photodyn Ther. 2018;21:367–374. doi:10.1016/j.pdpdt.2018.02.002

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