@article {Suzuki1323, author = {Akiko Suzuki and Pamela Leland and Hisataka Kobayashi and Peter L. Choyke and Elaine M. Jagoda and Tomio Inoue and Bharat H. Joshi and Raj K. Puri}, title = {Analysis of Biodistribution of Intracranially Infused Radiolabeled Interleukin-13 Receptor{\textendash}Targeted Immunotoxin IL-13PE by SPECT/CT in an Orthotopic Mouse Model of Human Glioma}, volume = {55}, number = {8}, pages = {1323--1329}, year = {2014}, doi = {10.2967/jnumed.114.138404}, publisher = {Society of Nuclear Medicine}, abstract = {Interleukin-13 Pseudomonas exotoxin (IL-13PE), a targeted agent for interleukin-13 receptor α2 (IL-13Rα2){\textendash}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{\textendash}positive but not to IL-13Rα2{\textendash}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.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/55/8/1323}, eprint = {https://jnm.snmjournals.org/content/55/8/1323.full.pdf}, journal = {Journal of Nuclear Medicine} }