Photoirradiation therapy of experimental malignant glioma with 5-aminolevulinic acid

Abstract

Photoirradiation therapy in combination with 5-ALA appears to damage experimental brain tumors selectively, with negligible damage to normal or perifocal edematous tissue.

Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5‐aminolevulinic acid induced protoporphyrin IX

“…PDT by means of 5-ALA induced PPIX is expected to induce less often and less severe side effects for several reasons: (1) The drug applied systemically (5-ALA) is itself not phototoxic, (2) 5-ALA induced PPIX has been shown to accumulate selectively within the tumor, and (3) a significant redistribution of the PS by peritumoral edema bulk flow does not seem to occur. Olzowy et al [17], for example, who investigated treatment effects of PDT by means of 5-ALA induced PPIX in an experimental glioma model, found selective phototoxic effects within the tumor (coagulative or hemorrhagic necrosis), whereas the damage to the normal or perifocal edematous tissue was negligible. Exactly these favorable characteristics of 5-ALA have led to a re-evaluation of iPDT as a potentially minimal invasive treatment modality and are an important prerequisite for accurate treatment planning.…”

“…Unfortunately, prolonged skin sensitization and damage to normal brain tissue due to the limited selectivity of the applied PS (Photofrin or Photofrin II) have obstructed the broad application of this potentially minimal invasive treatment concept. 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) has proven its high potential as a PS for PDT in several experimental studies [17][18][19][20] and has recently gained interest in neurosurgery [21,22] due to a selective tumor uptake and only minimal skin sensitization [23][24][25].…”

Efficacy of Systemic Radionuclide Therapy with p-131I-Iodo-l-Phenylalanine Combined with External Beam Photon Irradiation in Treating Malignant Gliomas

“…Therefore, overall survival (OS) generally ranges from a few months to about 1 y for glioblastoma multiforme, the most common malignant glioma (1)(2)(3)(4). To overcome these dismal prospects, various experimental therapies have been administered, including gene therapy, antisense treatment, boron neutron capture, locoregional radioimmunotherapy, ligand-toxin conjugate administration, or 5-aminolevulinic acid photodynamic therapy; methods for sensitizing glioma cells to apoptosis induction; or methods aiming at different targets such as the coagulation system, to name only a few (7)(8)(9)(10)(11)(12)(13). Unfortunately, all these efforts have failed to appreciably increase the median OS of patients with gliomas.…”

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

“…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).…”