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Article Abstract
The overexpression of HER2 has been strongly correlated with the pathogenesis and progression of breast cancer. Developing HER2-targeted PET tracers for noninvasive assessment of HER2 expression holds substantial clinical significance for screening patients suitable for HER2-targeted therapy, evaluating treatment efforts, and optimizing treatment. In this study, we employed computational simulation methods to develop peptide WC8 derived from trastuzumab, and designed HER2 targeting radiotracers [Ga]Ga-DOTA-WC8 for detecting the HER2 expression. The radiotracer demonstrated nanomolar affinity, high specificity, and favorable pharmacokinetics. PET imaging revealed that [Ga]Ga-DOTA-WC8 exhibited significant and specific uptake in HER2-positive breast cancer tissues, facilitating the rapid and accurate identification of HER2 expression. Notably, this radiotracer was successfully utilized to achieve direct visualization of tumor response to pyrotinib, a HER2 tyrosine kinase inhibitor. These findings suggest that the peptide-based radiotracer [Ga]Ga-DOTA-WC8 represents a promising tool for accurately monitoring of HER2 expression after treatment with HER2-targeting drugs.
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