TY - JOUR T1 - IL13RA2 targeted alpha particle therapy against glioblastoma JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 634 LP - 634 VL - 57 IS - supplement 2 AU - Anirudh Sattiraju AU - Darpan Pandya AU - Kiran Solingapuram Sai AU - Thaddeus Wadas AU - Denise Herpai AU - Waldemar Debinski AU - Akiva Mintz Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/634.abstract N2 - 634Objectives Glioblastoma (GBM) is the most common primary malignant brain tumor and is characterized by a dismal prognosis. Standard treatment options such as chemotherapy and radiation therapy have proven to be ineffective. We and others have therefore developed molecular strategies to specifically target IL13RA2, a glioblastoma restricted receptor expressed abundantly in about 75% of GBM patients. In this work, we for the first time radiolabeled a novel IL13RA2 targeting peptide (Pep-1L; Neuro Oncol. 2012 14(1):6-18. PMID: 21946118) with Actinium-225 (Ac-225), an alpha particle emitter, and demonstrated its in vivo potency.Methods For in vitro IL13RA2 binding confirmation, we initially radiolabeled Pep-1L with Copper-64 (Cu-64) using a NOTA crosslinker and performed a standard cell uptake assay using a human GBM cell line. We then radiolabeled Pep-1L with Ac-225 using a DOTA crosslinker and tested the therapeutic potential of Ac-225 labeled peptide in vivo by infusing it intracranially into orthotopic human GBM tumor xenografts in nude mice through convection enhanced delivery.Results We observed significant GBM cell uptake of our Cu-64 labeled peptide in vitro, which was specifically blocked with excess unlabeled peptide. Mice infused with our Ac-225 labeled peptide showed significantly greater overall survival (55 days) when compared to mice in control groups (30 days) (p<0.05). Double strand breaks, characteristic of alpha particle induced apoptosis were observed by using anti-gammaH2AX antibody.Conclusions Based on our findings, our alpha particle labeled IL13RA2 targeting peptide Pep-1L caused significant survival benefit in nude mice bearing orthotopic GBMs and warrants further investigation as a potential therapy for GBM patients in the future. ER -