Triple-negative breast cancer (TNBC) and urothelial bladder carcinoma (UBC) are aggressive cancers often diagnosed at advanced stages, leaving limited time for effective treatment decisions. Current imaging tools can be slow or lack the precision needed to identify key therapeutic targets in real time. Researchers have now developed a new PET tracer that visualizes a protein commonly overexpressed in these cancers within just four hours, enabling same-day imaging to speed diagnosis and optimize therapy selection.

Developed through a collaboration between the University of Wisconsin–Madison (Madison, WI, USA) and Peking University First Hospital (Beijing, China), the new tracer—64Cu-NOTA-EV-F(ab′)2?—targets nectin-4, a protein strongly linked to tumor growth in both cancer types. The team compared two tracer versions, one using a full-length antibody and another with a fragmented antibody, to determine the best balance of speed and accuracy. Using radiolabeled antibodies and PET imaging, researchers assessed binding affinity, specificity, and biodistribution across various tumor models expressing nectin-4.

In preclinical tests using xenograft mouse models of triple-negative breast and urothelial cancers, the fragmented tracer demonstrated rapid tumor accumulation with peak uptake at four hours post-injection. Compared with its full-length counterpart, the new version achieved higher tumor-to-background ratios and superior image clarity. The study, published in The Journal of Nuclear Medicine, confirmed that the tracer’s favorable pharmacokinetics enable high-contrast same-day imaging while minimizing radiation exposure.

This advancement represents a step forward in molecular imaging, providing oncologists with a noninvasive way to visualize nectin-4 expression and guide treatment selection in real time. The tracer could also support patient stratification, helping identify which individuals are most likely to benefit from nectin-4–targeted therapies. Researchers anticipate expanding this approach to additional cancers and PET isotopes, making precision imaging faster, safer, and more accessible for patients.

“This study demonstrates that 64Cu-NOTA-EV-F(ab′)2? exhibits rapid, specific, and sustained accumulation in tumor tissues in triple-negative breast and urothelial cancers, enabling accurate, noninvasive visualization of nectin-4 expression,” said Lei Kang, MD, PhD, co-author of the study. “In the future, this approach could extend to many other cancers, making molecular imaging faster, safer, and more patient-friendly.”

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