Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer with enhanced sensitivity and specificity

摘要

Poor prognosis of ovarian cancer (OvCa), the deadliest of the gynecologic malignancies, reflects major limitations associated with detection and diagnosis. Current methods lack high sensitivity to detect small tumors and high specificity to distinguish malignant from benign tissue, both impeding diagnosis of early and metastatic cancer stages and leading to costly and invasive surgeries. Tissue microarray analysis revealed that >98% of OvCa express the prolactin receptor (PRLR), forming the basis of a new molecular imaging strategy. We fused human placental lactogen (hPL), a specific and tight binding PRLR ligand, to magnetic resonance imaging (gadolinium) and near-infrared fluorescence imaging agents. Both in tissue culture and in mouse models, these imaging bioconjugates underwent selective internalization into OvCa cells via PRLR-mediated endocytosis. Compared to current clinical magnetic resonance imaging techniques, this targeted approach yielded both enhanced signal-to-noise ratio from accumulation of signal via selective internalization and improved specificity conferred by PRLR upregulation in malignant OvCa. These features endow PRLR-targeted imaging with the potential to transform OvCa detection.