A novel PET imaging approach allows simultaneous visualization of tumor progression and cardiac inflammatory responses during cancer treatment. Using this strategy, researchers demonstrated the efficacy of a new combination therapy that enhances tumor response while reducing cardiac inflammation. This new paradigm, announced at the Society of Nuclear Medicine and Molecular Imaging’s 2026 Annual Meeting, provides a more comprehensive assessment of treatment efficacy and supports more individualized clinical decision-making.
Immune checkpoint inhibitor (ICI)-based therapies have revolutionized cancer treatment and significantly improved patient survival. However, these treatments can also cause serious cardiac and vascular effects in some patients. Management of these cardiac complications may require interruption or discontinuation of ICI therapy, which may result in cancer progression.
Currently, there are no established molecular imaging methods to identify the occurrence of these cardiovascular immune-related adverse events in patients receiving ICI treatment. The CCR2 protein is expressed in both atherosclerotic plaques (driven by inflammation) and tumors, making it a promising biomarker for monitoring both. In this study, we evaluated a PET imaging approach to non-invasively detect immune-related adverse events in a cardiac tumor model using a CCR2-targeted radiotracer and a therapeutic strategy to reduce cardiac risks during treatment. ”
Dr. Jaume Otaegui, Postdoctoral Fellow, Washington University in St. Louis
Two cohorts of atherosclerotic mice were implanted with mouse oral cancer cells as a cardiac tumor model. The first group received ICI treatment or control treatment twice a week. PET imaging using the CCR2-targeted radiotracer 64Cu-DOTA-ECL1i was performed after 5 and 10 doses. 18F-FDG PET/CT was also performed for comparison. The second group of mice received ICI treatment for 3 weeks and received itacitinib (a Janus kinase 1 inhibitor) twice daily during the final 2 weeks of treatment. This cohort of mice underwent CCR2 PET imaging at the end of treatment.
64Cu-DOTA-ECL1i was found to bind effectively to CCR2 cells, improving PET/CT imaging of plaques and tumors compared to 18F-FDG. ICI treatment slowed tumor progression but did not affect CCR2 PET tumor signal. However, the CCR2 cardiac signal was significantly increased. Combination treatment with itacitinib showed improved tumor response, decreased CCR2 PET signal, and decreased inflammatory cells in the aorta compared to ICI treatment alone.
“CCR2 PET imaging may allow clinicians to detect adverse cardiovascular changes that occur during cancer treatment before they cause heart attack, myocarditis, or other serious complications,” Otaegui said. “Furthermore, our therapeutic approach combined with itacitinib ICI treatment could potentially be used to both reduce cardiovascular inflammation and enhance tumor control.”
He added: “Overall, this study points to more personalized and safer immunotherapies for patients, where cardiovascular complications can be imaged, predicted, and possibly reduced without compromising cancer treatment.”
64Cu-DOTA-ECL1i is currently being evaluated in imaging clinical trials across multiple disease indications, and ICI therapy has received U.S. Food and Drug Administration approval for several stages of head and neck cancer. Therefore, the imaging component of this study may be implemented in the near future. However, further research on combination therapy is still needed to more broadly validate the study results.
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Society of Nuclear Medicine and Molecular Imaging
