Development of a novel bio-imaging approach for assessing biodistribution of IL-13PE immunotoxin in targeting intracranial Interleukin-13 receptor positive glioblastoma tumors in mouse model

Wednesday, October 26, 2011 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center	FDA/CBER	IMAG-34

Authors

• A Suzuki
• T Fujisawa
• P Dover
• H Kobayashi
• T Inoue
• BH Joshi
• RK Puri

Abstract

We have previously demonstrated that Interleukin-13 Pseudomonas exotoxin (IL-13PE) has a remarkable antitumor activity in vitro and in vivo animal models of human glioma tumors. To study spatiotemporal distribution of IL-13PE in mouse model of brain tumor, we radiolabeled IL-13PE with I125 for its evaluation by nano-SPECT/CT after stereotactic injection. I125-IL-13PE was cytotoxic specifically to IL-13 receptor (IL-13R) positive U251 human glioma cells but not to IL-13R negative T98G cells. We tested its specific cytotoxic activity by blocking with 100X excess IL-13. Next, the tumors were implanted in mice brain with U251 cells and bolus dose of I125-IL-13PE was administered intracranially. SPECT/CT imaging revealed I125-IL-13PE accumulated in the brain tumor. As CED is a loco-regional drug delivery method for brain tumors that rely on a continuous pressure gradient to distribute drug into interstitial space, SPECT/CT imaging after CED of I125-IL-13PE is being performed to assess intracranial distribution. In conclusion, we developed a novel technology to radiolabel IL-13PE without loss of its cytotoxic activity, which is useful for SPECT imaging. We are currently evaluating critical parameters such as activity, distribution and toxicity of I125-IL-13PE in mouse brain to improve its delivery for an effective intracranial tumor therapy by CED.

back to top