Reston,
VA (September 20, 2025)--A promising new PET tracer can visualize a protein
that is commonly overexpressed in triple-negative breast and urothelial bladder
cancers within four hours, according to new research published in the September
issue of The Journal of Nuclear Medicine. This same-day imaging approach has the potential to save valuable
time in guiding treatment decisions and reduce unnecessary exposure to
ineffective therapies.
Triple-negative breast cancer (TNBC) is an
aggressive subtype that accounts for approximately 24 percent of newly
diagnosed breast cancer cases. Similarly, urothelial bladder carcinoma (UBC)
represents the most prevalent malignancy of the urinary tract, with urothelial
bladder cancer comprising about 90 percent of cases. Many patients are
diagnosed at advanced stages, underscoring the urgent need for reliable methods
for early detection and longitudinal monitoring.
"Nectin-4 is a protein that is overexpressed
in both TNBC and UBC and is a potential target to treat these diseases.
However, challenges remain in stratifying patients who are most likely to
benefit from nectin-4 therapies," said Weibo Cai, PhD, professor of radiology
and medical physics at the University of Wisconsin Madison. "We sought to
develop a PET tracer that allowed for rapid, high-contrast visualization of
nectin-4 expression, providing a clinically translatable approach for patient
stratification and real-time therapeutic monitoring."
A comprehensive evaluation of two PET tracers,
64Cu-NOTA-EV (conjugated with a full-length antibody) and 64Cu-NOTA-EV-F(ab′)2 (conjugated with a fragmented
antibody) was performed using various analytic methods. Nectin-4 expression in
human TNBC and UBC cell lines was assessed by flow cytometry and
immunofluorescence. Binding affinity and specificity were evaluated via cell
uptake and binding assays. Next, immuno-PET imaging and biodistribution studies
were conducted in mice bearing subcutaneous xenografts with varying levels of nectin-4
expression.
64Cu-NOTA-EV-F(ab′)2 exhibited
rapid tumor accumulation and high specificity in nectin-4 positive tumors, with
peak uptake observed at 4 hours after injection. EV-F(ab′)2 demonstrated
superior tumor-to-background ratios compared with 64Cu-NOTA-EV,
particularly in nectin-4 expressing models. Favorable pharmacokinetics of EV-F(ab′)2 allowed for same-day imaging and
reduced radiation exposure relative to intact antibodies.
"This study demonstrates that 64Cu-NOTA-EV-F(ab′)2 exhibits
rapid, specific, and sustained accumulation in tumor tissues in TNBC and UBC
models, enabling accurate, noninvasive visualization of nectin-4 expression," noted Lei Kang, MD, PhD, professor of nuclear medicine at Peking University
First Hospital in Beijing, China. "In the future, this approach could expand to
many other cancers, targets, and PET isotopes, making molecular imaging faster,
safer, and more patient-friendly."