Effects of 5-ALA dose on resection of glioblastoma

Michael, Alex P.; Watson, Victoria L.; Ryan, Daniel; Delfino, Kristin; Bekker, Simon; Cozzens, Jeffrey W.

doi:10.1007/s11060-019-03100-7

Cited by 25 publications

(20 citation statements)

References 29 publications

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“…It is recommended that a fluorescent imaging probe be selective towards the tumor cells while sparing adjacent tissue. An example of this is the application of the Food and Drug Administration (FDA)-approved metabolic precursor of fluorescent porphyrin IX (PpIX), named 5-aminolevulinic acid (5-ALA), for intraoperative MRI, with a recommended dose of 20 mg/kg body weight [21]. The 5-ALA accumulates in non-necrotic marginal glioblastoma tissue [32].…”

Section: Fluorescent Magnetic Resonance Imagingmentioning

confidence: 99%

“…The 5-ALA accumulates in non-necrotic marginal glioblastoma tissue [32]. It is metabolized in the mitochondria of glioma cells, where it produces protoporphyrin IX, which fluoresces under deep blue light, allowing for the immediate identification of tumor tissue [21,22]. In the study by Ji et al, the authors performed analysis of the fluorescence-guided surgery in numerous gliomas, while focusing on epidemiological data of the fluorescence pattern and its impact on extent of resection [20].…”

Section: Fluorescent Magnetic Resonance Imagingmentioning

confidence: 99%

“…In addition, complete resection was performed in 89.6% fluorescence-positive gliomas compared to 75% of fluorescence-negative gliomas. In a retrospective cohort study, Michael et al tested the effect of different doses of 5-ALA on residual tumor volume and patient overall survival [21]. However, the authors did not find a correlation between either low (10-30 mg/kg) or high (40-50 mg/kg) doses and overall survival.…”

Section: Fluorescent Magnetic Resonance Imagingmentioning

confidence: 99%

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Nanomedicine and Immunotherapy: A Step Further towards Precision Medicine for Glioblastoma

et al. 2020

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Owing to the advancement of technology combined with our deeper knowledge of human nature and diseases, we are able to move towards precision medicine, where patients are treated at the individual level in concordance with their genetic profiles. Lately, the integration of nanoparticles in biotechnology and their applications in medicine has allowed us to diagnose and treat disease better and more precisely. As a model disease, we used a grade IV malignant brain tumor (glioblastoma). Significant improvements in diagnosis were achieved with the application of fluorescent nanoparticles for intraoperative magnetic resonance imaging (MRI), allowing for improved tumor cell visibility and increasing the extent of the surgical resection, leading to better patient response. Fluorescent probes can be engineered to be activated through different molecular pathways, which will open the path to individualized glioblastoma diagnosis, monitoring, and treatment. Nanoparticles are also extensively studied as nanovehicles for targeted delivery and more controlled medication release, and some nanomedicines are already in early phases of clinical trials. Moreover, sampling biological fluids will give new insights into glioblastoma pathogenesis due to the presence of extracellular vesicles, circulating tumor cells, and circulating tumor DNA. As current glioblastoma therapy does not provide good quality of life for patients, other approaches such as immunotherapy are explored. To conclude, we reason that development of personalized therapies based on a patient’s genetic signature combined with pharmacogenomics and immunogenomic information will significantly change the outcome of glioblastoma patients.

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Section: Fluorescent Magnetic Resonance Imagingmentioning

confidence: 99%

Section: Fluorescent Magnetic Resonance Imagingmentioning

confidence: 99%

Section: Fluorescent Magnetic Resonance Imagingmentioning

confidence: 99%

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Nanomedicine and Immunotherapy: A Step Further towards Precision Medicine for Glioblastoma

et al. 2020

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“…The current standard 5-ALA dose, 20 mg/kg three hours prior to surgery or PDT, might be lower than optimal. Doses of 50 mg/kg can be given prior to glioma surgery that are well-tolerated and result in stronger intraoperative fluorescence [37,38]. CTCAE grade 1 skin redness and peeling were seen at higher doses.…”

Section: -Ala Enhances Kev and Mev Cytotoxicitymentioning

confidence: 99%

A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen

Kast¹,

Michael

Sardi

et al. 2020

Brain Sciences

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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 O2 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 O2 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 O2 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.

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“…Photodynamic therapy (PDT) utilizes light juxtaposed with a photosensitizer in the presence of oxygen, resulting in potentially cytolytic effects due to reactive oxygen species (ROS) production. One well-studied European Medicines Agency (EMA) and United States Food and Drug Administration (FDA) approved photosensitizer, 5-aminolevulinic acid (5-ALA), is utilized for various clinical PDT applications [9,10], including actinic keratosis [11,12] and basal cell carcinoma [13], as well as its use as a surgical guidance tool for glioblastomas [14,15] and gliomas [16]. Intrinsically, 5-ALA is a heme precursor in a metabolic process within the mitochondria that synthesizes protoporphyrin IX (PPIX) [17,18].…”

Section: Introductionmentioning

confidence: 99%

Metalloporphyrin Pd(T4) Exhibits Oncolytic Activity and Cumulative Effects with 5-ALA Photodynamic Treatment against C918 Cells

Leviskas

Vályi-Nagy

Munirathinam

et al. 2020

IJMS

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Photodynamic therapy is a non-invasive method where light activates a photosensitizer bound to cancer cells, generating reactive oxygen species and resulting in cell death. This study assessed the oncolytic potential of photodynamic therapy, comparing European Medicines Agency and United States Food and Drug Administration-approved 5-aminolevulinic acid (5-ALA) to a metalloporphyrin, Pd(T4), against a highly invasive uveal melanoma cell line (C918) in two- and three-dimensional models in vitro. Epithelial monolayer studies displayed strong oncolytic effects (>70%) when utilizing Pd(T4) at a fraction of the concentration, and reduced pre-illumination time compared to 5-ALA post-405 nm irradiance. When analyzed at sub-optimal concentrations, application of Pd(T4) and 5-ALA with 405 nm displayed cumulative effects. Lethality from Pd(T4)-photodynamic therapy was maintained within a three-dimensional model, including the more resilient vasculogenic mimicry-forming cells, though at lower rates. At high concentrations, modality of cell death exhibited necrosis partially dependent on reactive oxygen species. However, sub-optimal concentrations of photosensitizer exhibited an apoptotic protein expression profile characterized by increased Bax/Bcl-2 ratio and endoplasmic stress-related proteins, along with downregulation of apoptotic inhibitors CIAP-1 and -2. Together, our results indicate Pd(T4) as a strong photosensitizer alone and in combination with 5-ALA against C918 cells.

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Effects of 5-ALA dose on resection of glioblastoma

Cited by 25 publications

References 29 publications

Nanomedicine and Immunotherapy: A Step Further towards Precision Medicine for Glioblastoma

Nanomedicine and Immunotherapy: A Step Further towards Precision Medicine for Glioblastoma

A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen

Metalloporphyrin Pd(T4) Exhibits Oncolytic Activity and Cumulative Effects with 5-ALA Photodynamic Treatment against C918 Cells

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