October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
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) |
FDA/CBER |
CANCER-17 |
* FARE Award Winner
Authors
- A Suzuki
- P Leland
- PL Choyke
- T Inoue
- H Kobayashi
- BH Joshi
- RK Puri
Abstract
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.
