Innovative PET Tracer Facilitates Same-Day Imaging for Breast and Bladder Cancers

A groundbreaking positron emission tomography (PET) tracer has been developed, enabling visualization of a protein that is frequently overexpressed in both triple-negative breast cancer (TNBC) and urothelial bladder cancer (UBC) in under four hours. This advancement, detailed in a recent study published in the Journal of Nuclear Medicine, holds significant promise for expediting treatment decisions and minimizing unnecessary exposure to ineffective therapies.

Triple-negative breast cancer is a notably aggressive form, responsible for approximately 24% of all new breast cancer diagnoses. Urothelial bladder carcinoma is the predominant malignancy of the urinary tract, accounting for about 90% of cases. Many patients discover their conditions at advanced stages, highlighting an urgent need for reliable early detection and ongoing monitoring methods.

Researchers identified Nectin-4 as a potential target for therapy, as it is overexpressed in TNBC and UBC. However, stratifying patients who are likely to benefit from nectin-4 therapies remains a challenge. In an effort to address this, the team aimed to create a PET tracer that could provide rapid and high-contrast visualization of nectin-4 expression, ultimately facilitating patient stratification and real-time monitoring of treatment efficacy.

The study assessed two PET tracers: 64Cu-NOTA-EV, which is conjugated with a full-length antibody, and 64Cu-NOTA-EV-F(ab´)2, linked to a fragmented antibody. The research involved evaluating Nectin-4 expression in human TNBC and UBC cell lines through flow cytometry and immunofluorescence. Binding affinity and specificity were analyzed via cell uptake and binding assays. Additionally, immuno-PET imaging and biodistribution studies were conducted using mice with subcutaneous xenografts exhibiting varying levels of Nectin-4 expression.

Results indicated that the 64Cu-NOTA-EV-F(ab´)2 tracer demonstrated rapid tumor accumulation and high specificity for Nectin-4 positive tumors, with peak uptake occurring four hours post-injection. The EV-F(ab´)2 variant showcased superior tumor-to-background ratios compared to the full-length antibody, particularly in models expressing Nectin-4. The favorable pharmacokinetics of EV-F(ab´)2 facilitated same-day imaging while reducing radiation exposure in comparison to intact antibodies.

This research illustrates that 64Cu-NOTA-EV-F(ab´)2 achieves swift, specific, and sustained accumulation in tumor tissues related to TNBC and UBC, thereby enabling accurate and non-invasive imaging of Nectin-4 expression. Future applications of this approach may extend to various other cancers, targets, and PET isotopes, enhancing the speed, safety, and patient-friendliness of molecular imaging.