title: 5-Aminolevulinic acid-induced protoporphyrin IX levels in tissue of human malignant brain tumors.
abstract: Protoporphyrin IX (PpIX) produced from exogenous, orally administered 5-aminolevulinic acid (ALA) displays high tumor-selective uptake and is being successfully employed for fluorescence-guided resection (FGR) of human malignant gliomas. Furthermore, the phototoxicity of PpIX can be utilized for photodynamic therapy (PDT) of brain tumors, which has been shown previously. Here, the absolute PpIX concentration in human brain tissue was investigated following oral ALA administration (20 mg kg(-1) b.w.). An extraction procedure was used to quantify PpIX in macroscopic tissue samples, weighing 0.013-0.214 g, obtained during FGR. The PpIX concentration was significantly higher in vital grade IV tumors (5.8 ± 4.8 μm, mean ± SD, range 0-28.2 μm, n = 8) as compared with grade III tumors (0.2 ± 0.4 μm, mean ± SD, range 0-0.9 μm, n = 4). There was also a large heterogeneity within grade IV tumors with PpIX displaying significantly lower levels in infiltration zones and necrotic regions as compared with vital tumor parts. The average PpIX concentration in vital grade IV tumor parts was in the range previously shown sufficient for PDT-induced tissue damage following irradiation. However, the feasibility of PDT for grade III brain tumors and for grade IV brain tumors displaying mainly necrotic tissue areas without solid tumor parts needs to be further investigated.
authors.affiliation: Laser-Forschungslabor, University Clinic Großhadern, Munich, Germany. ann.johansson@med.uni-muenchen.de
authors.forename: Ann
authors.initials: A
authors.lastname: Johansson
authors.forename: Gesa
authors.initials: G
authors.lastname: Palte
authors.forename: Oliver
authors.initials: O
authors.lastname: Schnell
authors.forename: Jörg-Christian
authors.initials: JC
authors.lastname: Tonn
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.forename: Herbert
authors.initials: H
authors.lastname: Stepp
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011524:Protoporphyrins / Q000378:metabolism*
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX