Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model

Angell-Petersen, Even; Spetalen, Signe; Madsen, Steen J.; Sun, Chung Ho; Peng, Qian; Carper, Stephen W.; Sioud, Mouldy; Hirschberg, Henry

doi:10.3171/jns.2006.104.1.109

Cited by 80 publications

(63 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Exogenous 5-ALA results in selective protoporphyrin IX (PpIX) accumulation in tumor cells including malignant gliomas to a greater extent compared to normal brain tissue [2][3][4][5][6]. 5-ALA induced fluorescence of PpIX, which has a maximum absorption around a wavelength of 400 nm, can be visualized by modified neurosurgical operating microscopes [7] and has shown to identify residual tumor during the resection of malignant gliomas in experimental and clinical settings [3,5,8].…”

Section: -Aminolevulinic Acid (5-ala) Is a Naturally Occurring Intermentioning

confidence: 99%

Multiphoton excitation fluorescence microscopy of 5‐aminolevulinic acid induced fluorescence in experimental gliomas

Kantelhardt

Diddens²,

Leppert

et al. 2008

Lasers Surg Med

View full text Add to dashboard Cite

show abstract

Section: -Aminolevulinic Acid (5-ala) Is a Naturally Occurring Intermentioning

confidence: 99%

Multiphoton excitation fluorescence microscopy of 5‐aminolevulinic acid induced fluorescence in experimental gliomas

Kantelhardt

Diddens²,

Leppert

et al. 2008

Lasers Surg Med

View full text Add to dashboard Cite

show abstract

“…Quite selective accumulation of 5-ALA-induced PP IX has been demonstrated for malignant glioma cells in vitro (23,24) and in vivo (25,26) as well as for many other tumour cells. In addition, due to the photosensitizing properties of PP IX, photodynamic treatment of malignant glioma might be considered as a promising additional therapeutic option, which is currently investigated in vitro (27,28) and in vivo (29)(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

Photodynamic therapy of malignant glioma with hypericin: Comprehensive in vitro study in human glioblastoma cell lines

Ritz¹,

Wein²,

Dietz³

et al. 2007

Int J Oncol

View full text Add to dashboard Cite

Abstract. The poor prognosis of patients suffering from malignant glioma requires further efforts. Photodynamic therapy (PDT) might be a therapeutic option to increase surgical radicality. Hypericin (HY) exhibit high phototoxicity to malignant cells and accumulates to a higher extent in glioblastoma cells as compared to neurons. Therefore, the impact of various experimental parameters on cytotoxicity, intracellular accumulation and phototoxicity of HY was quantitatively assessed in the three human glioblastoma cell lines U373 MG, LN229 and T98G. Additionally, intracellular location of HY was studied with fluorescence microscopic techniques. For all three cell lines, no cytotoxicity was found for incubation concentrations up to 5 μM. For short-time incubation (2 h), maximum HY fluorescence was achieved at an incubation concentration of about 5 μM. However, uptake kinetics of HY was dependent on its incubation concentration. Moreover, increase in HY fluorescence was negligible at 4˚C, which strongly indicates that the compound is taken up by an energy-dependent process. HY exhibited high phototoxicity (at 595 nm) in all three cell lines with ID 50 -values ranging from 0.15 J/cm 2 to 0.22 J/cm 2 , but sensitivity decreased in the order U373 MG > LN229 > T98G. However, assessment of phototoxicity at different wavelengths revealed that highest cell inactivation was achieved at 600 nm. Fluorescence microscopy showed that HY fluorescence arose predominantly from the perinuclear region and the nuclear membrane. Fluorescence pattern of HY was significantly different from those observed for organelle markers staining lysosomes or mitochondria. Location of HY in the plasma membrane was proven by total internal reflection fluorescence microscopy. Thus, the present study demonstrates that glioblastoma cells can be effectively inactivated by HY-PDT after short-time incubation and exposure to low light doses. These results obtained in cell culture are encouraging and justify further evaluation HY-PDT for the treatment of malignant glioma in animal experiments.

show abstract

“…In our study a total fluence dose of 15 J/cm 2 was chosen as we believed from preliminary experimentation that this dose would result in a sufficient PDT effect and the delivery of the total light dose at a fluence rate of 70 mW/cm 2 would be feasible for a "one-shot" intraoperative PDT treatment. In vitro studies have found PDT treatment with low fluence doses and low fluence rates to be more effective than low fluence doses with high fluence rates [36]. Finally, plates were measured for 'post' PpIX fluorescence levels (following light irradiation).…”

Section: Ppix Fluorescence Monitoring In Vitromentioning

confidence: 99%

The Effects of Iron Chelation and Hypoxic or Hyperoxic Oxygen Manipulation on the Accumulation/Photobleaching of Protoporphryin IX and Cytotoxcity in Human Glioma Cells

Blake¹,

Allen²,

Curnow³

2013

J Anal Bioanal Tech

View full text Add to dashboard Cite

Background and objective: Gliomas remain the most common and problematic primary brain tumors to treat given their mobile and invasive characteristics, resulting in a 5 years survival rate of less than 5%. Recently the administration of photosensitive fluorescent drugs has been utilized to aid in the identification and resection of gliomas. In this experimental investigation of human glioma cells the effect of iron chelation and oxygenation manipulation, firstly on the accumulation of the clinically useful photosensitizer protoporphyrin IX (PpIX) and subsequently on PpIX photobleaching and cytotoxicity on irradiation, has been examined with the aim of improving fluorescence-guided resection/photodynamic therapy (PDT). Materials and methods:Cells were incubated at concentrations of 5%, 20% or 40% oxygen for 24 hours prior to and for 3 hours following the administration of the PpIX precursors aminolevulinic acid (ALA), methyl levulinate (MAL) or hexyl aminolevulinate (HAL) with or without the iron chelator 1,2-diethyl-3-hydroxypyridin-4-one hydrochloride (CP94). PpIX levels were monitored using a fluorescence plate reader (excitation filter 400 ± 30 nm; emission filter 645 ± 40 nm). Cells were irradiated with 15 J/cm 2 red lights and viability measured using the neutral red uptake assay.Results: Manipulation of the oxygen environment and/or co administration of CP94 with PpIX precursors resulted in significant changes in both PpIX accumulation and photobleaching. Incubation with ALA/ MAL at 5% or 40% oxygen produced the greatest levels of PpIX and photobleaching respectively. Both these parameters were further elevated through co administration of CP94. The combination of hyperoxygenation and CP94 administration significantly increased photobleaching (a marker of PDT effect) but not cytotoxicity in this experimental system. Conclusions:PpIX accumulation was greatest when the cells were grown in hypoxic (5% oxygen) conditions (mimicking the in vivo situation) with ALA/MAL+CP94. Fluorescence-guided resection of glioma may therefore be improved through the addition of the iron chelating adjuvant CP94.

show abstract

Influence of light fluence rate on the effects of photodynamic therapy in an orthotopic rat glioma model

Abstract: Treatment with ALA PDT induced pronounced necrosis in tumors only if the light was delivered at a low rate. The treatment prolonged the survival for tumor-bearing animals.

Cited by 80 publications

References 43 publications

Multiphoton excitation fluorescence microscopy of 5‐aminolevulinic acid induced fluorescence in experimental gliomas

Multiphoton excitation fluorescence microscopy of 5‐aminolevulinic acid induced fluorescence in experimental gliomas

Photodynamic therapy of malignant glioma with hypericin: Comprehensive in vitro study in human glioblastoma cell lines

The Effects of Iron Chelation and Hypoxic or Hyperoxic Oxygen Manipulation on the Accumulation/Photobleaching of Protoporphryin IX and Cytotoxcity in Human Glioma Cells

Contact Info

Product

Resources

About