Los Angeles -- A novel PET imaging approach enables simultaneous visualization of tumor progression and cardiac inflammatory responses during cancer treatment. Using this strategy, researchers demonstrated the effectiveness of a new combination therapy that enhances tumor response while reducing cardiac inflammation. This new paradigm, presented at the Society of Nuclear Medicine and Molecular Imaging 2026 Annual Meeting, offers a more comprehensive assessment of therapeutic impact, supporting more personalized clinical decision‑making.
Immune checkpoint inhibitor (ICI)-based therapies have revolutionized cancer treatment and substantially improved patients' survival. These treatments, however, can also lead to serious heart and vascular adverse effects in a subset of patients. Management of these cardiac complications may require interruption or discontinuation of ICI therapy, potentially resulting in cancer progression.
"Currently, there is no established molecular imaging approach to identify the development of these cardiovascular immune-related adverse events in patients receiving ICI treatments," said Jaume Otaegui, PhD, postdoctoral researcher at Washington University in St. Louis. "The CCR2 protein is expressed in both atherosclerotic plaques (which are driven by inflammation) and tumors, making it a promising biomarker for monitoring both. In this study, we evaluated a PET imaging approach to noninvasively detect immune-related adverse events in a cardio‑oncology model using a CCR2-targeted radiotracer, as well as a therapeutic strategy to reduce cardiac risk during treatment."
Two cohorts of atherosclerotic mice were implanted with mouse oral carcinoma cells as a cardio-oncology model. The first group received ICI treatment or a control treatment twice a week. PET imaging using the CCR2-targeted radiotracer 64Cu-DOTA-ECL1i was performed after five and 10 doses; 18F-FDG PET/CT was also performed for comparison. The second group of mice received ICI treatment for three weeks, and during the last two weeks of treatment, itacitinib (a Janus kinase 1 inhibitor) was given twice a day. This cohort of mice underwent CCR2 PET imaging at the end of the treatment.
64Cu-DOTA-ECL1i was found to effectively bind to CCR2 cells, allowing for better PET/CT imaging of plaque and tumors compared to 18F-FDG. ICI treatment slowed down tumor progression but did not affect CCR2 PET tumor signal; CCR2 cardiac signal, however, was significantly increased. Co-treatment with itacitinib showed better tumor response, reduced CCR2 PET signal, and fewer inflammatory cells in the aorta compared to ICI treatment alone.
"CCR2 PET imaging could potentially allow clinicians to detect harmful cardiovascular changes that occur during cancer treatment before they result in heart attack, myocarditis, or other serious complications," said Otaegui. "Additionally, our therapeutic approach of combining itacitinib ICI treatment could be used to both reduce cardiovascular inflammation and enhance tumor control."
He continued, "Overall, for patients, this work points toward more personalized and safer immunotherapy -- where we can image, anticipate, and possibly mitigate cardiovascular complications without compromising cancer treatment."
64Cu-DOTA-ECL1i is currently being evaluated in clinical trials for imaging across multiple disease indications, and ICI therapy has received U.S. Food and Drug Administration approval for several stages of head and neck cancer. Consequently, the imaging component of this work may be implemented in the near‑term. Further studies on the combination therapy, however, are still needed to provide broader validation of the study's findings.
Abstract 262118. "Theranostics of immune-related adverse events in cardio-oncology based on CCR2 PET imaging," Jaume R. Otaegui, Divangana Lahad, Xiuli Zhang, Hannah P. Luehmann, Gyu Seong Heo, Robert Crowder, Sidharth Puram, Kory Lavine, and Yongjian Liu, Washington University, St. Louis, Missouri.
