title: Deferoxamine iron chelation increases delta-aminolevulinic acid induced protoporphyrin IX in xenograft glioma model.
abstract: Exogenous administration of delta-aminolevulinic acid (delta-ALA) leads to selective accumulation of protoporphyrin IX (PpIX) in brain tumors, and has shown promising results in increasing extent of resection in fluorescence-guided resection (FGR) of brain tumors. However, this approach still suffers from heterogeneous staining and so some tumor margins may go undetected because of this variation in PpIX production. The aim of this study was to test the hypothesis that iron chelation therapy could increase the level of fluorescence in malignant glioma tumors. Mice implanted with xenograft U251-GFP glioma tumor cells were given a 200 mg kg(-1) dose of deferoxamine (DFO), once a day for 3 days prior to delta-ALA administration. The PpIX fluorescence observed in the tumor regions was 1.9 times the background in animal group without DFO, and 2.9 times the background on average, in the DFO pre-treated group. A 50% increase in PpIX fluorescence contrast in the DFO group was observed relative to the control group (t-test P-value = 0.0020). These results indicate that iron chelation therapy could significantly increase delta-ALA-induced PpIX fluorescence in malignant gliomas, pointing to a potential role of iron chelation therapy for more effective FGR of brain tumors.
authors.affiliation: Dartmouth Medical School, Dartmouth College, Hanover, NH, USA. Pablo.A.Valdes@dartmouth.edu
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Valdés
authors.forename: Kimberley
authors.initials: K
authors.lastname: Samkoe
authors.forename: Julia A
authors.initials: JA
authors.lastname: O'Hara
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.forename: Keith D
authors.initials: KD
authors.lastname: Paulsen
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
mesh_terms: D000622:Aminolevulinic Acid; D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology; D003676:Deferoxamine / Q000494:pharmacology*; D003952:Diagnostic Imaging / Q000379:methods*; D005453:Fluorescence; D005910:Glioma / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D051379:Mice; D011524:Protoporphyrins / Q000032:analysis*; D014183:Transplantation, Heterologous
chemical_list: D007502:Iron Chelating Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D003676:Deferoxamine