Triple-negative breast cancer (TNBC), which represents 15-20% of all breast cancer cases, is one of the most aggressive subtypes, with a five-year survival rate of about 40%. Due to its significant heterogeneity and high recurrence rate, treatment can be particularly challenging. However, recent research has introduced a novel PET radiotracer that can effectively visualize Nectin-4, a promising biomarker associated with TNBC. Published in The Journal of Nuclear Medicine, the study suggests that this new PET tracer could play a pivotal role in diagnosing, treating, and monitoring this aggressive form of cancer, potentially improving clinical outcomes for patients.

Nectin-4 is a biomarker that is highly expressed in TNBC, but effective imaging tools targeting this marker have been lacking until now. To address this critical need, scientists at the Fudan University Shanghai Cancer Center (Shanghai, China) developed a series of Nectin-4-targeted radiotracers and tested their efficacy in detecting Nectin-4 in TNBC. The researchers created three different radiotracers—68Ga-FZ-NR-1, 68Ga-FZ-NR-2, and 68Ga-FZ-NR-3—and assessed their targeting ability and specificity both in vitro and in vivo, including in a murine tumor model.

After conducting preclinical experiments and screenings, the 68Ga-FZ-NR-1 radiotracer demonstrated the highest targeting efficacy and was selected for further evaluation in a first-in-human study. PET/CT scans using 68Ga-FZ-NR-1 were performed on nine TNBC patients. Positive lesions were biopsied and analyzed using immunohistochemistry to assess Nectin-4 expression levels. The PET/CT imaging with 68Ga-FZ-NR-1 effectively identified tumors in these patients, which was later confirmed by 18F-FDG PET/CT. Biopsy results revealed that the areas identified as positive by 68Ga-FZ-NR-1 PET/CT had high Nectin-4 expression, confirming the tracer’s ability to specifically target and detect Nectin-4 in TNBC tumors.

“The significance of this research lies in its potential to revolutionize the diagnostic landscape for TNBC patients,” said Shaoli Song, PhD, director of nuclear medicine in the Department of Nuclear Medicine at the Fudan University Shanghai Cancer Center. “With the introduction of 68Ga-FZ-NR-1, we are now able to detect tumors with greater precision and provide patients with more reliable diagnostic information. This advancement has the potential to improve treatment outcomes by enabling more accurate disease assessment and personalized therapeutic strategies. We anticipate that this work will stimulate further research into the development and clinical application of Nectin-4-targeted imaging agents. Ultimately, this could enhance the diagnostic value of nuclear medicine not only for TNBC, but also for other cancers.” 

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