Novel radiolabeled antibody developed for diagnosis and treatment of solid tumors

Reston, VA (April 17, 2025)—A newly developed radiolabeled antibody that targets the cancer antigen IL13Rα2 has been found to be highly specific, binding only to cancer cells and not to the related antigen IL13Rα1, which is widely expressed in healthy tissues. Tested in multiple cancer types, the radiolabeled antibody was effective at delineating malignancies at a low injected mass dose and has the potential to be translated into radioimmunotherapy applications. This research was published in the April issue of The Journal of Nuclear Medicine.

Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma, melanoma, and breast cancer. IL13Rα2 has limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor detection.

“So far, no IL13Rα2-targeting antibodies for diagnostic and therapeutic (theranostic) applications exist in the clinic,” said Simone Krebs, MD, associate professor at the University of Texas MD Anderson Cancer Center in Houston, Texas. “My colleagues and I sought to develop a radiolabeled antibody that would achieve high and prolonged tumor uptake and retention, facilitating delivery of cytotoxic radiation predominantly to tumors while sparing normal tissues.” The antibody development project was undertaken during her tenure at Memorial Sloan Kettering Cancer Center.

In the study, five novel human anti-IL13Rα2 antibodies (KLG-1–5) were developed. In vitro binding properties and target specificity were assessed, and in vivo ⁸⁹Zr-immuno-PET was conducted in a glioblastoma mouse model. Upon selection of KLG-3 as the leading candidate, a mass dose titration study was conducted. Next, ex vivo biodistribution results were used to determine effective dosimetry of ¹⁷⁷Lu-labeled KLG-3 therapy. Targeting with KLG-3 was also evaluated in a melanoma mouse model.

Lead candidate anti-IL13Rα2 antibody KLG-3 validated highly specific target binding in human glioblastoma and melanoma models, resulting in high-contrast PET images with minimal accumulation in off-target healthy tissues. Prospective dosimetry of its ¹⁷⁷Lu-labeled counterpart suggested therapeutic efficacy at relatively low injected activities, supporting further pursuit of KLG-3 as a potential radioimmunotherapy.

“These results demonstrate a significant advance in the use of IL13Rα2 as a viable target in cancer therapy,” stated Krebs. “Implementation of the targeting moieties developed in this study may lead to highly specific and efficacious tumor-targeted drugs with little side effects to the patients.

She continued, “IL13Rα2 is known to be a harbinger of immunosuppression, and thus, IL13Rα2-targeted Immuno-PET may identify this molecular phenotype, which could aid in patient selection and an understanding of who may benefit from combinatorial strategies.”

The authors of “IL13Rα2-Targeting Antibodies for Immuno-PET in Solid Malignancies” include Leah Gajecki, Lukas M. Carter, Melina Kumpf, and Samantha Lovibond, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; Irina V. Lebedeva, Yu-Rou Liao, Daisy Ambriz, David P. Andrew, and Manuel Baca, Sanders Tri-Institutional Therapeutics Discovery Institute, New York, New York; Justin S. Hachey, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, and Department of Pharmacology, Weill Cornell Graduate School of Medicine Sciences, New York, New York; Maya S. Graham, Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, and Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, New York; Michael Postow, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Jason S. Lewis, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York, Molecular Pharmacology Program, Sloan Kettering Institute, New York, New York, and Department of Radiology, Weill Cornell Medicine, New York, New York; Heiko Schöder and Darren R. Veach, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, and Department of Radiology, Weill Cornell Medicine, New York, New York; Steven M. Larson, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, Molecular Pharmacology Program, Sloan Kettering Institute, New York, New York, and Department of Radiology, Weill Cornell Medicine, New York, New York; and Simone Krebs, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, Department of Radiology, Weill Cornell Medicine, New York, New York, Department of Nuclear Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas; and Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, Texas.

Visit the JNM website for the latest research, and follow our new Twitter and Facebook pages @JournalofNucMed or follow us on LinkedIn.

###

Please visit the SNMMI Media Center for more information about molecular imaging and precision imaging. To schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or rmaxey@snmmi.org.

About JNM and the Society of Nuclear Medicine and Molecular Imaging
The Journal of Nuclear Medicine (JNM) is the world’s leading nuclear medicine, molecular imaging and theranostics journal, accessed 15 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field. Current and past issues of The Journal of Nuclear Medicine can be found online at http://jnm.snmjournals.org.

JNM is published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an international scientific and medical organization dedicated to advancing nuclear medicine, molecular imaging, and theranostics—precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes. For more information, visit www.snmmi.org.