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

Journal of Nuclear Medicine

Pamela Leland¹  Bharat H. Joshi¹  Elaine M. Jagoda¹  Raj K. Puri¹  Akiko Suzuki¹  Tomio Inoue¹  Hisataka Kobayashi¹  Peter L. Choyke¹ 

关键词: SPECT;    brain tumor;    convection-enhanced delivery;    biodistribution;    IL-13PE;    radioiodination;   

DOI  :  10.2967/jnumed.114.138404

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown