RT Journal Article
SR Electronic
T1 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
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1323
OP 1329
DO 10.2967/jnumed.114.138404
VO 55
IS 8
A1 Akiko Suzuki
A1 Pamela Leland
A1 Hisataka Kobayashi
A1 Peter L. Choyke
A1 Elaine M. Jagoda
A1 Tomio Inoue
A1 Bharat H. Joshi
A1 Raj K. Puri
YR 2014
UL http://jnm.snmjournals.org/content/55/8/1323.abstract
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.