ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

Fisher, Carl; Niu, Carolyn; Foltz, Warren D.; Chen, Yonghong; Sidorova-Darmos, Elena; Eubanks, James H.; Lilge, Lothar

doi:10.1371/journal.pone.0181654

Cited by 33 publications

(23 citation statements)

References 60 publications

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“…Increasing the PDT depth selectivity is feasible by modifications to the threshold values for which various approaches have been proposed, including hypothermia for ALA-induced PpIX, 44 adjuvant chemotherapy 45 or use of targeted nanoparticles, 46 and may need to be considered if the SUR of the photosensitizer is significantly lower.…”

Section: Discussionmentioning

confidence: 99%

Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer

Lilge

et al. 2020

J. Biomed. Opt.

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Significance: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradient. Aim: To determine how a high PDT selectivity can be maintained throughout the bladder wall considering other efficacy determining parameters, in particular, the average optical properties of the mucosal layer governing the fluence rate multiplication factor, as well as the bladder shape and the position of the emitter in relationship to the bladder wall. Approach: We present three irradiance monitoring systems and evaluate their ability to enable selective bladder PDT considering previously determined photodynamic threshold values for the bladder cancer, mucosa and urothelium in a preclinical model, and the photosensitizer's specific uptake ratio. Monte Carlo-based light propagation simulations performed for six human bladders at the time of therapy for a range of tissue optical properties. The performance of one irradiance sensing device in a clinical phase 1B trial is presented to underline the impact of irradiance monitoring, and it is compared to the Monte Carlo-derived dose surface histogram. Results: Monte Carlo simulations showed that irradiance monitoring systems need to comprise at least three sensors. Light scattering inside the bladder void needs to be minimized to prevent increased heterogeneity of the irradiance. The dose surface histograms vary significantly depending on the bladder shape and bladder volume but are less dependent on tissue optical properties. Conclusions: We demonstrate the need for adequate irradiance monitoring independent of a photosensitizer's specific uptake ratio.

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Section: Discussionmentioning

confidence: 99%

Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer

Lilge

et al. 2020

J. Biomed. Opt.

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“…A tumor selective increase in PpIX accumulation was also observed, when glioma cells, primary rat embryonic neurons, and astrocytes were exposed to hypothermia during incubation with 5‐ALA . When hypothermia was applied in vivo, a neuroprotective effect against PDT was observed, also increasing the selectivity of GBM PDT .…”

Section: Fluorescence Guided Surgerymentioning

confidence: 86%

5‐ALA in the management of malignant glioma

Stepp¹,

2018

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Background: Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard. Aims: This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients. Materials and Methods: From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience. Results and Discussion: The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT). Conclusion: 5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018.

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“…Laboratory research on application of light for therapy of GBM has not yet produced conclusive results but this does not mean that this strategy is not viable. Most, if not all, PDT experiments on gliomas used commercially available glioma cell lines [60][61][62][63][64][65][66][67]. As is the case with many cancer cell lines, there is always uncertainty about the origin of these cells, about possible contamination with other cell lines (e.g., HeLa cervical cancer cells, a common contaminating cell), and the effect of culturing which may lead to the accumulation of mutations with every cell division [68].…”

Section: Challenges For Development Of Pdt For Gbmmentioning

confidence: 99%

Using Light for Therapy of Glioblastoma Multiforme (GBM)

et al. 2020

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Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumour with extremely poor prognosis. The current standard of care for newly diagnosed GBM includes maximal surgical resection followed by radiotherapy and adjuvant chemotherapy. The introduction of this protocol has improved overall survival, however recurrence is essentially inevitable. The key reason for that is that the surgical treatment fails to eradicate GBM cells completely, and adjacent parenchyma remains infiltrated by scattered GBM cells which become the source of recurrence. This stimulates interest to any supplementary methods which could help to destroy residual GBM cells and fight the infiltration. Photodynamic therapy (PDT) relies on photo-toxic effects induced by specific molecules (photosensitisers) upon absorption of photons from a light source. Such toxic effects are not specific to a particular molecular fingerprint of GBM, but rather depend on selective accumulation of the photosensitiser inside tumour cells or, perhaps their greater sensitivity to the effects, triggered by light. This gives hope that it might be possible to preferentially damage infiltrating GBM cells within the areas which cannot be surgically removed and further improve the chances of survival if an efficient photosensitiser and hardware for light delivery into the brain tissue are developed. So far, clinical trials with PDT were performed with one specific type of photosensitiser, protoporphyrin IX, which tends to accumulate in the cytoplasm of the GBM cells. In this review we discuss the idea that other types of molecules which build up in mitochondria could be explored as photosensitisers and used for PDT of these aggressive brain tumours.

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ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

Cited by 33 publications

References 60 publications

Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer

Minimal required PDT light dosimetry for nonmuscle invasive bladder cancer

5‐ALA in the management of malignant glioma

Using Light for Therapy of Glioblastoma Multiforme (GBM)

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