HER2 and CD24 emerge as promising radiotheranostic targets in endometrial cancer

Two molecular targets-human epidermal growth factor 2 (HER2) and cluster of differentiation 24 (CD24)-are highly promising candidates for new nuclear diagnostics and therapeutics for endometrial cancer, according to new research published in The Journal of Nuclear Medicine. PET imaging of these targets could play a significant role in the management of the disease, helping clinicians identify patients who are likely to respond to targeted therapeutics. 

Endometrial cancer is the most common gynecologic malignancy worldwide, and its incidence and mortality rates have increased over the past decade. Although early-stage disease is effectively treated via hysterectomy, a dearth of molecularly targeted therapies means that prognoses are far poorer for those with disseminated or recurrent disease.

“Taken together, these factors clearly indicate that the development of novel approaches to the imaging and therapy of endometrial cancer is an urgent clinical need,” remarked Brian M. Zeglis, PhD, professor of chemistry at Hunter College, City University of New York in New York City. “To address this issue, my colleagues and I explored three biomarkers-HER2, mucin-16 (MUC16), and CD24-as potential radiotheranostic targets for endometrial cancer.” 

In the study, researchers first evaluated the expression of HER2, MUC16, and CD24 antigens in endometrial cancer and healthy uterine and healthy endometrial cell lines as well as in patient-derived endometrial cancer tissues. Next, immunoPET probes targeting each of these antigens-⁸⁹Zr-DFO-trastuzumab (HER2), ⁸⁹Zr-DFO-AR9.6 (MUC16), and ⁸⁹Zr-DFO-ATG-031 (CD24)-were interrogated via PET imaging and biodistribution experiments in cell line and patient-derived murine models of endometrial cancer. 

Researchers found that endometrial cancer cells and tissue samples expressed elevated levels of HER2, MUC16, and CD24 compared with healthy control cells and tissue samples. The three immunoPET probes exhibited significantly different behavior in mice bearing subcutaneous endometrial cancer xenografts: ⁸⁹Zr-DFO-ATG-031 provided the highest tumor uptake and tumor-to-background contrast; ⁸⁹Zr-DFO-trastuzumab produced moderate yet promising results; and ⁸⁹Zr-DFO-AR9.6 yielded substandard images. Subsequent imaging experiments in mice bearing patient-derived xenografts reinforced the potential of the CD24- and HER2-targeted immunoPET probes.

“The clear potential of HER2 and CD24 as molecular targets in endometrial cancer raises the question of how these two targets could be exploited for clinical nuclear medicine,” said Zeglis. “It is our hope that this work leads to the application of new HER2- and CD24-targeted radiotheranostics in endometrial cancer. More broadly, we hope that this investigation spurs increased interest in our field in this understudied disease.”