In vivo PET imaging and biodistribution of radiolabeled EV and antibody fragments in xenograft fashions of TNBC. (A) Consultant PET photographs of mice bearing MDA-MB-468, BT474, and MDA-MB-231 tumors at 1, 4, 12, 24, and 48-h after injection of [64Cu]Cu-NOTA-EV or [64Cu]Cu-NOTA-EV-F(ab′)2, with or with out blocking. Tumors are indicated by white arrows. (B) Quantitative biodistribution information (%ID/g) of radiotracers in tumor and main organs over time. (C) T/H and T/M ratios over time as decided by region-of-interest picture analyses. T/NT = tumor to nontumor. Credit score: Journal of Nuclear Drugs (2025). DOI: 10.2967/jnumed.125.270132
A promising new PET tracer can visualize a protein that’s generally overexpressed in triple-negative breast and urothelial bladder cancers inside 4 hours, in response to analysis revealed within the Journal of Nuclear Drugs. This same-day imaging method has the potential to avoid wasting beneficial time in guiding therapy selections and cut back pointless publicity to ineffective therapies.
Triple-negative breast most cancers (TNBC) is an aggressive subtype that accounts for roughly 24% of newly identified breast most cancers circumstances. Equally, urothelial bladder carcinoma (UBC) represents essentially the most prevalent malignancy of the urinary tract, with urothelial bladder most cancers comprising about 90% of circumstances. Many sufferers are identified at superior levels, underscoring the pressing want for dependable strategies 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,” mentioned Weibo Cai, Ph.D., professor of radiology and medical physics on the College 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 complete analysis 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 carried out utilizing varied analytic strategies. Nectin-4 expression in human TNBC and UBC cell strains was assessed by movement cytometry and immunofluorescence. Binding affinity and specificity had been evaluated by way of cell uptake and binding assays.
Subsequent, immuno-PET imaging and biodistribution research had been performed in mice bearing subcutaneous xenografts with various ranges of nectin-4 expression.
64Cu-NOTA-EV-F(ab′)2 exhibited speedy tumor accumulation and excessive specificity in nectin-4 constructive tumors, with peak uptake noticed at 4 hours after injection. EV-F(ab′)2 demonstrated superior tumor-to-background ratios in contrast with 64Cu-NOTA-EV, notably in nectin-4 expressing fashions. Favorable pharmacokinetics of EV-F(ab′)2 allowed for same-day imaging and diminished radiation publicity 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,” famous Lei Kang, MD, Ph.D., professor of nuclear drugs at Peking College 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.”
Extra data:
Wenpeng Huang et al, [64Cu]Cu-NOTA-EV-F(ab′)2 Permits Similar-Day Immuno-PET Imaging of Nectin-4 in Triple-Unfavorable Breast and Urothelial Bladder Cancers, Journal of Nuclear Drugs (2025). DOI: 10.2967/jnumed.125.270132
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New PET tracer allows same-day imaging of triple-negative breast and urothelial cancers (2025, September 22)
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