Abstract 1831: PET/CT imaging of interleukin-13 receptor alpha-2-targeted peptide to glioblastoma after locoregional delivery

2017 
Glioblastoma (GBM) is the most aggressive and common primary malignant astrocytoma which is characterized by tumor heterogeneity, infiltrating margins. Radiotherapy, chemotherapy and experimental targeted therapies have been ineffective at meaningfully increasing patient survival. One significant shortcoming of systemically delivered therapies is their inability to cross the blood brain barrier (BBB) and access infiltrating tumor cells. Therefore, in this work, we tested the potential of locoregionally targeting GBM via IL13Rα2, which we discovered to be expressed on greater than 75% of GBMs. To accomplish this, we intracranially infused copper-64 ( 64 Cu) radiolabeled IL13Rα2 specific peptide Pep-1L, previously developed by Pandya et al., into mice bearing IL13Rα2 expressing orthotopic GBMs. Small animal micro PET/CT imaging showed ~2-fold greater tumor specific localization and lower volume of distribution of 64 Cu-Pep-1L within brains of mice. Post-PET biodistribution study showed greater retention of 64 Cu-Pep-1L 4 hours (%ID/g = 20.85± 0.65) and 24 hours (%ID/g = 14.65± 0.30) post infusion when compared to similarly infused 64 Cu radiolabeled scrambled control peptide 4 hours (%ID/g = 10.73± 2.02) and 24 hours (%ID/g = 5.97± 1.47) post infusion. These results demonstrate that Pep-1L efficiently targets IL13Rα2 expressing GBMs in vivo upon loco-regional delivery and can effectively deliver potential therapeutic agents to GBM tumors while sparing normal brain. This work was supported by the American Cancer Society Mentored Research Scholar grant # 124443-MRSG-13-121-01-CDD (Mintz), 1R01CA179072-01A1 (Mintz), P30 CA012197 (Pasche), R01CA07414519 (Debinski) and the Translational Imaging Program (TIP) of the Wake Forest CTSA (UL1TR001420). Citation Format: Anirudh Sattiraju, Ang Xuan, Frankis Almaguel, Denise Herpai, Waldemar Debinski, Akiva Mintz, Kiran Kumar Solingapuram Sai. PET/CT imaging of interleukin-13 receptor alpha-2-targeted peptide to glioblastoma after locoregional delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1831. doi:10.1158/1538-7445.AM2017-1831
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