Fundamentals of 5‐aminolevulinic acid photodynamic therapy and diagnosis: An overview

Malik, Zvi

doi:10.1002/tbio.201900022

Cited by 23 publications

(19 citation statements)

References 29 publications

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“…5-Aminolevulinic acid (ALA), methyl aminolevulinate (MAL; Metvix), and Hexvix/Cysview are precursors of protoporphyrin IX, which absorbs at 630 nm [ 28 , 29 ]. They were granted FDA approvals and are used to treat glioblastoma, basal cell carcinoma, Bowen disease, prostate, bladder, and colon cancers [ 30 , 31 , 32 ]. Meta-tetrahydroxy phenyl chlorin (m-THPC, temoporfin), excitation wavelength of ~652 nm, is approved in the EU to treat biliary and pancreatic cancers and breast cancer metastases.…”

Section: Photodynamic Therapy In Treating Cancermentioning

confidence: 99%

Liposome Photosensitizer Formulations for Effective Cancer Photodynamic Therapy

2021

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Photodynamic therapy (PDT) is a promising non-invasive strategy in the fight against that which circumvents the systemic toxic effects of chemotherapeutics. It relies on photosensitizers (PSs), which are photoactivated by light irradiation and interaction with molecular oxygen. This generates highly reactive oxygen species (such as 1O2, H2O2, O2, ·OH), which kill cancer cells by necrosis or apoptosis. Despite the promising effects of PDT in cancer treatment, it still suffers from several shortcomings, such as poor biodistribution of hydrophobic PSs, low cellular uptake, and low efficacy in treating bulky or deep tumors. Hence, various nanoplatforms have been developed to increase PDT treatment effectiveness and minimize off-target adverse effects. Liposomes showed great potential in accommodating different PSs, chemotherapeutic drugs, and other therapeutically active molecules. Here, we review the state-of-the-art in encapsulating PSs alone or combined with other chemotherapeutic drugs into liposomes for effective tumor PDT.

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Section: Photodynamic Therapy In Treating Cancermentioning

confidence: 99%

Liposome Photosensitizer Formulations for Effective Cancer Photodynamic Therapy

2021

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“…Several clinical studies have explored the use of 5-aminolevulinic acid (5-ALA) as a photosensitizer precursor [ 6 , 7 , 8 , 9 , 10 ], which has some intriguing advantages over other photosensitizers for treating high grade gliomas: There is much less concern about unspecific photosensitization during circulation and tissue distribution, as 5-ALA itself is not photoactive [ 11 ]. Clinically approved, 5-ALA is also widely used for protoporphyrin IX (PpIX)-based fluorescence-guided resection of malignant gliomas [ 11 , 12 , 13 ]. The photosensitizer PpIX is produced in the mitochondria of malignant glioma cells with a high selective accumulation compared to adjacent tissue [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Clinically approved, 5-ALA is also widely used for protoporphyrin IX (PpIX)-based fluorescence-guided resection of malignant gliomas [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Interrelation between Spectral Online Monitoring and Postoperative T1-Weighted MRI in Interstitial Photodynamic Therapy of Malignant Gliomas

Aumiller

Heckl

Quach

et al. 2021

Cancers

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In a former study, interstitial photodynamic therapy (iPDT) was performed on patients suffering from newly diagnosed glioblastoma (n = 11; 8/3 male/female; median age: 68, range: 40–76). The procedure includes the application of 5-ALA to selectively metabolize protoporphyrin IX (PpIX) in tumor cells and illumination utilizing interstitially positioned optical cylindrical diffuser fibers (CDF) (2–10 CDFs, 2–3 cm diffusor length, 200 mW/cm, 635 nm, 60 min irradiation). Intraoperative spectral online monitoring (SOM) was employed to monitor treatment light transmission and PpIX fluorescence during iPDT. MRI was used for treatment planning and outcome assessment. Case-dependent observations included intraoperative reduction of treatment light transmission and local intrinsic T1 hyperintensity in non-contrast-enhanced T1-weighted MRI acquired within one day after iPDT. Intrinsic T1 hyperintensity was observed and found to be associated with the treatment volume, which indicates the presence of methemoglobin, possibly induced by iPDT. Based on SOM data, the optical absorption coefficient and its change during iPDT were estimated for the target tissue volumes interjacent between evaluable CDF-pairs at the treatment wavelength of 635 nm. By spatial comparison and statistical analysis, it was found that observed increases of the absorption coefficient during iPDT were larger in or near regions of intrinsic T1 hyperintensity (p = 0.003). In cases where PpIX-fluorescence was undetectable before iPDT, the increase in optical absorption and intrinsic T1 hyperintensity tended to be less. The observations are consistent with in vitro experiments and indicate PDT-induced deoxygenation of hemoglobin and methemoglobin formation. Further investigations are needed to provide more data on the time course of the observed changes, thus paving the way for optimized iPDT irradiation protocols.

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“…Accumulation of PpIX may be induced by the administration of its biosynthetic precursor 5-aminolevulinic acid (ALA)this is the principle of ALA-PDT [6] and also fluorescence photodiagnosis (PDD) using administered ALA [7,8]. The production of ALA in heme biosynthesis is normally tightly controlled by heme itself functioning as a feedback inhibitor of the enzyme, ALA synthase, but this mechanism is bypassed by introduction of exogeneous ALA, and build-up of PpIX results due to slow conversion of the latter to heme by insertion of a ferrous ion into its tetrapyrrole core [7].…”

Section: Introductionmentioning

confidence: 99%