Deferoxamine Iron Chelation Increases δ‐Aminolevulinic Acid Induced Protoporphyrin IX in Xenograft Glioma Model

Abstract

Exogenous administration of δ‐aminolevulinic acid (δ‐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 δ‐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 δ‐ALA‐induced PpIX fluorescence in malignant gliomas, pointing to a potential role of iron chelation therapy for more effective FGR of brain tumors.