Novel Theranostic Approach for Radioimmunotherapy Achieves Curative Responses in Colorectal Cancer Tumors

Reston, VA (April 30, 2026)--A new pretargeted radioimmunotherapy (PRIT) technique has been shown to be safe and effective in eradicating tumors from a preclinical colorectal cancer model. The multi-step theranostic approach delivers alpha-emitting radiation directly to tumors while limiting exposure to healthy tissues. This research was published in the May issue of The Journal of Nuclear Medicine.

Radiopharmaceutical therapy, especially with molecularly targeted alpha-emitting radionuclides, is proving to be transformative in oncology. Among the most promising is the matched ²⁰³Pb/²¹²Pb theranostic pair. The toxic effects of ²¹²Pb on the kidneys, however, remain a concern.

"With the toxicity issues that come along with Pb-based radionuclides, PRIT can be especially helpful in making sure the radiation only goes where it is needed,"  said Sarah M. Cheal, PhD, assistant professor at Weill Cornell Medicine in New York. "In this study, my colleagues and I developed a novel PRIT approach for colorectal cancer, assessed its biodistribution, and tested various treatment regimens to see what was most effective."

The PRIT approach targeted GPA33, an antigen that is overexpressed in 95 percent of colorectal tumors. Researchers first performed serial biodistribution and SPECT/CT imaging studies of GPA33-targeted ²⁰³Pb/²¹²Pb-DOTA-based PRIT to assess feasibility. Once confirmed, dosimetry was evaluated and various treatment regimens were evaluated in mice bearing human colorectal cancer tumors.

Researchers established that two consecutive doses separated by 48 hours led to prolonged survival--including histologic cures in three out of five mice in the cohort. Mice in this treatment group exhibited normal bone marrow and overall preserved kidney function.

"This PRIT approach produced a combination of effective tumor targeting with minimal toxicity, demonstrating a highly favorable therapeutic window for curative radioimmunotherapy,"  said Nai-Kong V. Cheung, MD, PhD, Enid A. Haupt Chair in Pediatric Oncology at Memorial Sloan Kettering Cancer Center in New York.  "We know there is a significant unmet need for more effective and low-toxicity therapies for advanced colorectal cancer. This study represents an early but important step towards developing a radiopharmaceutical strategy that can meet that need."

"What's more,"  he said, "because this platform is modular, it can be adapted to many different tumor targets. What is learned for one target could be exploited for others, either for the same tumor, or across a wider range of cancers. The ²⁰³/²¹²Pb theranostic pairing is especially promising, and our findings support its emerging potential in nuclear medicine and precision oncology."

Graphical Abstract: ²⁰³/²¹²Pb-DOTA-based pretargeted radioimmunotherapy against the glycoprotein GPA33 antigen is safe and effective in preclinical models of human colorectal cancer. 

The authors of "Preclinical ^203/212Pb-DOTA Based Pretargeted Radioimmunotherapy in Nude Mice Bearing Established Human Colorectal Cancer Xenografts" include Brett A. Vaughn, Daniela Burnes Vargas, and Sarah M. Cheal, Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York; 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; Shin Seo and Blesida Punzalan, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York; Sara S. Rinne, Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, and Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York; Edward K. Fung, Department of Medical Physics, Weill Cornell Medicine, New York, New York; Hong Xu, Hong-Fen Guo, and Nai-Kong V. Cheung, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York; Guangbin Yang and Ouathek Ouerfelli, Organic Synthesis Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York; Sebastian E. Carrasco and Samantha St. Jean, Laboratory of Comparative Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine and Rockefeller University, New York, New York; and Steven M. Larson, Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York, and Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.

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