Pretargeted Dual-Isotope Radionuclide Therapy in Colorectal Cancer

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A combination of alpha- and beta-radionuclide therapy may be feasible, tolerable, and effective in colorectal cancer, according to preclinical findings presented by Rinne et al at the 2024 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting (Abstract 241498). The new approach could allow for the simultaneous delivery of two radionuclides directly to the tumor cells while significantly reducing the risk of treatment-related side effects.


Although targeted radionuclide therapy has proven effective, some patients may not respond to the selected radionuclide therapy, experience relapse, or develop treatment resistance. Tumor heterogeneity may also present a barrier to targeted radionuclide therapy, since differences in tumor make-up can impact effectiveness.

“Combining radionuclides with different radiobiological properties and administering them simultaneously may help overcome some of these issues,” explained lead study author Sara S. Rinne, PhD, a postdoctoral associate in Radiology at Weill Cornell Medicine. “The use of both alpha- and beta-emitting nuclides could better address tumor heterogeneity [as a result of] their varied penetration depths and ability to induce different radiobiological effects—thus creating more complex damage to the tumor and offering a potentially successful treatment approach for a larger patient population,” she said.

Study Methods and Results

In the new study, researchers evaluated the therapeutic efficacy of simultaneously administered lutetium Lu-177/actinium Ac-225 pretargeted radioimmunotherapy compared with separately administered Lu-177 and Ac-225 therapies in mice with human colorectal cancer xenografts. They then conducted biodistribution and autoradiography experiments to determine feasibility and dosage. The mice with human colorectal cancer xenografts were treated with mono- or combination therapy and monitored for several months.

The researchers discovered that combination therapy could bind to the colorectal cancer xenografts. Further, combined, pretargeted Lu-177/Ac-225 radioimmunotherapy was equally as potent as monotherapy in inducing tumor shrinkage and cures and was well tolerated in the preclinical model.


“The ability to simultaneously deliver different radioisotopes with complementary radiobiological properties creates new opportunities for improving therapy outcomes and improving patient care,” emphasized Dr. Rinne. “Furthermore, our study’s results highlight the great promise and versatility of pretargeted radioimmunotherapy to treat with curative intent. Overall, pretargeted dual-isotope [radionuclide] therapy has the potential to be a versatile approach to help a larger patient population and overcome existing barriers to successful targeted radionuclide therapy,” she concluded.

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