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Assessment of Bio-distribution of Interleukin-13 Pseudomonas Exotoxin, A Targeted Agent for Interleukin-13 Receptor Expressing Brain Tumor by SPECT/CT Analysis in vivo

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)



* FARE Award Winner


  • A Suzuki
  • P Leland
  • PL Choyke
  • T Inoue
  • H Kobayashi
  • BH Joshi
  • RK Puri


Previously, we demonstrated that interleukin-13 Pseudomonas exotoxin (IL-13PE) is a potent immunotoxin for IL-13 receptor α2 (IL-13Rα2) - positive tumors and examined for safety and effectiveness in pre-clinical and clinical glioblastoma multiforme (GBM) studies. However, its distribution after intra-cranial convection-enhanced delivery (CED) has not been studied. We radiolabeled IL-13PE with Iodine-125 (I-125) and determined its binding and biological activity in vitro and its distribution in vivo. I-125-IL-13PE is found to be cytotoxic in a concentration dependent manner to IL-13Rα2 positive U251 glioma cells but not negative T98G cells. Binding and cytotoxic activities were blocked by 100-fold excess of IL-13 indicating specific binding. Athymic nude mice with intracranially implanted U251 tumors were given stereotactic intratumoral injections of I-125-IL-13PE by either a bolus injection or 3-day-CED for micro-SPECT/CT. SPECT/CT imaging demonstrated retention of I-125-IL-13PE in U251 tumors. Drug distribution by CED showed a 12-fold higher volume of distribution and maintained detectable drug levels compared to bolus injection. These results are being confirmed by autoradiography on brain sections. We conclude that IL-13PE can be successfully radiolabeled with I-125 without loss of binding and cytotoxic activity and that I-125-IL-13PE administered by CED showed greater distribution than the bolus route.

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