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.