Research Papers:

Peptide-based PET imaging of the tumor restricted IL13RA2 biomarker

Kiran Kumar Solingapuram Sai _, Anirudh Sattiraju, Frankis G. Almaguel, Ang Xuan, Stephanie Rideout, Rahul S. Krishnaswamy, JoAnn Zhang, Denise M. Herpai, Waldemar Debinski and Akiva Mintz

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Oncotarget. 2017; 8:50997-51007. https://doi.org/10.18632/oncotarget.16549

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Kiran Kumar Solingapuram Sai1,*, Anirudh Sattiraju1,*, Frankis G. Almaguel1, Ang Xuan1, Stephanie Rideout1, Rahul S. Krishnaswamy1, JoAnn Zhang2, Denise M. Herpai3, Waldemar Debinski3 and Akiva Mintz1

1Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, USA

2MicroPET/CT Imaging Section, TriFoil Imaging, Chatsworth, CA, USA

3Department 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: [email protected]

Akiva Mintz, email: [email protected]

Keywords: positron emission tomography (PET), high-grade glioma, doxycycline, biodistribution, IL13RA2

Received: January 25, 2017    Accepted: February 27, 2017    Published: March 24, 2017


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. [64Cu]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 [64Cu]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 [64Cu]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 [64Cu]Pep-1L selectively binds hIL13RA2-expressing tumors and validates Pep-1L as an effective platform to deliver diagnostics and therapeutics to IL13RA2-expressing cancers.

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