PT  - JOURNAL ARTICLE
AU  - Suzuki, Akiko
AU  - Leland, Pamela
AU  - Kobayashi, Hisataka
AU  - Choyke, Peter L.
AU  - Jagoda, Elaine M.
AU  - Inoue, Tomio
AU  - Joshi, Bharat H.
AU  - Puri, Raj K.
TI  - Analysis of Biodistribution of Intracranially Infused Radiolabeled Interleukin-13 Receptor–Targeted Immunotoxin IL-13PE by SPECT/CT in an Orthotopic Mouse Model of Human Glioma
AID  - 10.2967/jnumed.114.138404
DP  - 2014 Aug 01
TA  - Journal of Nuclear Medicine
PG  - 1323--1329
VI  - 55
IP  - 8
4099  - http://jnm.snmjournals.org/content/55/8/1323.short
4100  - http://jnm.snmjournals.org/content/55/8/1323.full
SO  - J Nucl Med2014 Aug 01; 55
AB  - Interleukin-13 Pseudomonas exotoxin (IL-13PE), a targeted agent for interleukin-13 receptor α2 (IL-13Rα2)–expressing tumors, has been administered intracranially by convection-enhanced delivery (CED) for glioma therapy in several clinical trials including a randomized phase 3 clinical trial. However, its intracranial distribution was not optimally evaluated. We investigated the intracranial distribution of radiolabeled IL-13PE after CED in a murine model of glioblastoma multiforme. Methods: IL-13PE was radiolabeled with Na125I and evaluated for its activity in vitro in receptor-positive U251 or -negative T98G human glioma cell lines. Gliomas were grown in nude mice after intracranial implantation with U251 cells, and 125I-IL-13PE was stereotactically administered by bolus or CED for 3 d, followed by micro-SPECT/CT imaging. SPECT images were evaluated quantitatively and compared with histology and autoradiography results. Results: The radioiodination technique resulted in a specific and biologically active 125I-IL-13PE, which bound and was cytotoxic to IL-13Rα2–positive but not to IL-13Rα2–negative tumor cells. Both the binding and the cytotoxic activities were blocked by a 100-fold excess of IL-13, which indicated the specificity of binding and cytotoxicity. SPECT/CT imaging revealed retention of 125I-IL-13PE administered by CED in U251 tumors and showed significantly higher volumes of distribution and maintained detectable drug levels for a longer period of time than the bolus route. These results were confirmed by autoradiography. Conclusion: IL-13PE can be radioiodinated without the loss of specificity, binding, or cytotoxic activity. Intracranial CED administration produces a higher volume of distribution for a longer period of time than the bolus route. Thus, CED of IL-13PE is superior to bolus injection in delivering the drug to the entire tumor.