Peptide-based PET imaging of the tumor restricted IL13RA2 biomarker

This is the authors' abstract. We don't add key points for this paper.

// Kiran Kumar Solingapuram Sai 1, * , Anirudh Sattiraju 1, * , Frankis G. Almaguel 1 , Ang Xuan 1 , Stephanie Rideout 1 , Rahul S. Krishnaswamy 1 , JoAnn Zhang 2 , Denise M. Herpai 3 , Waldemar Debinski 3 and Akiva Mintz 1 1 Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA 2 MicroPET/CT Imaging Section, TriFoil Imaging, Chatsworth, CA, USA 3 Department of Cancer Biology, Brain Tumor Center of Excellence, Wake Forest School of Medicine, Winston Salem, NC, USA * These authors have contributed equally to this work Correspondence to: Kiran Kumar Solingapuram Sai, email: ksolinga@wakehealth.edu Akiva Mintz, email: amintz@wakehealth.edu Keywords: positron emission tomography (PET), high-grade glioma, doxycycline, biodistribution, IL13RA2 Received: January 25, 2017     Accepted: February 27, 2017     Published: March 24, 2017 ABSTRACT Peptides that target cancer cell surface receptors are promising platforms to deliver diagnostic and therapeutic payloads specifically to cancer but not normal tissue. IL13RA2 is a tumor-restricted receptor found to be present in several aggressive malignancies, including in the vast majority of high-grade gliomas and malignant melanoma. This receptor has been successfully targeted for diagnostic and therapeutic purposes using modified IL-13 ligand and more recently using a specific peptide, Pep-1L. In the current work, we establish the in vitro and in vivo tumor binding properties of radiolabeled Pep-1L, designed for tumor imaging. We radiolabeled Pep-1L with Copper-64 and demonstrated specific cell uptake in the IL13RA2-over expressing G48 glioblastoma cell line having abundant IL13RA2 expression. [ 64 Cu]Pep-1L binding was blocked by unlabeled ligand, demonstrating specificity. To demonstrate in vivo tumor uptake, we intravenously injected into tumor-bearing mice and demonstrated that [ 64 Cu]Pep-1L specifically bound tumors at 24 hours, which was significantly blocked (3-fold) by pre-injecting unlabeled peptide. To further demonstrate specificity of Pep-1L towards IL13RA2 in vivo , we exploited an IL13RA2-inducible melanoma tumor model that does not express receptor at baseline but expresses abundant receptor after treatment with doxycycline. We injected [ 64 Cu]Pep-1L into mice bearing IL13RA2-inducible melanoma tumors and performed in vivo PET/CT and post-necropsy biodistribution studies and found that tumors that were induced to express IL13RA2 receptor by doxycycline pretreatment bound radiolabeled Pep-1L 3-4 fold greater than uninduced tumors, demonstrating receptor specificity. This work demonstrates that [ 64 Cu]Pep-1L selectively binds hIL13RA2-expressing tumors and validates Pep-1L as an effective platform to deliver diagnostics and therapeutics to IL13RA2-expressing cancers.