image: Figure 1. Autoradiography images of GPA33(+) SW1222 xenograft sections acquired using an ionizing-radiation quantum imaging detector (iQID) camera. The images effectively illustrate that the DOTA-PRIT (DOTA pretargeted radioimmunotherapy) approach can be used to simultaneously deliver 225Ac and 177Lu to tumors. Mice were injected with 177Lu- or 225Ac-radioligand alone (first and second row, respectively), or a 177Lu/225Ac mixture (row 3 and 4), after pretargeting with anti-GPA33/anti-DOTA bispecific antibody. First column shows the combined signal (177Lu and 225Ac together), second column (⍺-counts) shows uptake of 225Ac, and third column (β-counts) show 177Lu-uptake. Fourth column shows an overlay of the 225Ac-signal (red) and 177Lu-signal (green).
Credit: Image courtesy of Rinne et al., Weill Cornell Medicine, New York, New York.
Toronto, Ontario—Combination of alpha- and beta-radionuclide therapy is feasible, tolerable, and effective for colorectal cancer, according to preclinical research presented at the 2024 Society of Nuclear Medicine and Molecular Imaging Annual meeting. This new approach allows simultaneous delivery of two radionuclides directly to tumor cells while significantly reducing the risk of treatment-related side effects.
Despite the successes of targeted radionuclide therapy, challenges remain; some patients do not respond to the chosen radionuclide therapy, while others experience relapse or develop treatment resistance. Tumor heterogeneity presents another obstacle for targeted radionuclide therapy as 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,” said Sara S. Rinne, postdoctoral associate in radiology at Weill Cornell Medicine in New York, New York. “The use of both alpha- and beta-emitting nuclides could better address tumor heterogeneity due to 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.”
The study aimed to evaluate the feasibility and therapeutic efficacy of simultaneously administered 177Lu/225Ac pretargeted radioimmunotherapy and compare it to separate 177Lu and 225Ac therapies on human colorectal cancer xenografts in mice. Biodistribution and autoradiography experiments were conducted to determine feasibility and dosage. Mice with colorectal cancer xenografts were then treated with mono- or combination therapy and monitored over several months.
Biodistribution and autoradiography experiments confirmed that the combination therapy could bind to colorectal cancer xenografts. Combined 177Lu/225Ac pretargeted radioimmunotherapy was equally as potent as mono-therapy 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,” noted Rinne. “Furthermore, our study’s results highlight the great promise and versatility of pretargeted radioimmunotherapy to treat with curative intent. Overall, pre-targeted dual-isotope therapy has the potential to be a versatile approach to help a larger patient population and overcome existing barriers to successful targeted radionuclide therapy.”
Abstract 241498. “177Lu/225Ac pretargeted dual-isotope therapy for treatment of GPA33(+) colorectal cancer,” Sara S. Rinne, Brett Vaughn, Hong-fen Guo, Daniela Burnes Vargas, Niloufar Salehi, Hong Xu, Darren Veach, Claire Vanpouille-Box, Brian Miller, Steven Larson, Nai-Kong Cheung, Sarah Cheal, Weill Cornell Medicine, New York, New York.
Link to Session
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All 2024 SNMMI Annual Meeting abstracts can be found online.
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Article Title
177Lu/225Ac pretargeted dual-isotope therapy for treatment of GPA33(+) colorectal cancer
Article Publication Date
11-Jun-2024