Researchers from the University of Wisconsin-Madison reported on results of an experiment in mice in which they administered the radionuclide 90Y-NM600 as part of a study on the impact the treatment would have on making tumors more susceptible to the effects of immunotherapy. Immunotherapy has had limited success in the treatment of prostate cancer, according to a press statement released by SNMMI.
Different groups of mice were given either a high or low dose of 90Y-NM600, and tumor growth and survival were measured for 60 days. The same doses of 90Y-NM600 were administered to a separate group of mice; these animals were sacrificed to analyze the radionuclide's immunological effects in the tumor microenvironment and lymphoid tissues, such as flow cytometry, immunohistochemistry, and Luminex cytokine profiling.
The researchers used PET/CT scans to analyze the effects of the treatment, with the data indicating that 90Y-NM600 immunomodulates the prostate tumor microenvironment, modifying tumor-infiltrating lymphocyte populations, upregulating checkpoint molecules, and promoting the release of proinflammatory cytokines. What's more, the radionuclide's inflammatory-promoting effect was demonstrated at relatively low radiation doses, and it did not produce systemic toxicity, according to the statement.
PET/CT image shows uptake and retention of 86Y-NM600 (imaging agent) in immunocompetent mice bearing prostate tumors. PET imaging data was employed to estimate tumor dosimetry and prescribe an immunomodulatory 90Y-NM600 dose as a therapy agent. Image courtesy of Reinier Hernandez, PhD, et al, University of Wisconsin-Madison.
The researchers believe that the findings show promise for the integration of 90Y-NM600 with immunotherapy of prostate cancer, which could prove particularly beneficial for patients with advanced disease, according to lead author Reinier Hernandez, PhD, of the university. Hernandez and colleagues hope to advance this "immunomodulation" concept into a phase I clinical trial.
They are also excited about the technique's impact at low radiation doses, which could lead to patient-specific image-based dosimetry techniques that preserve the benefits of immunomodulation.
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