Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity.
Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity.
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DOI：
10.1158/0008-5472.can-16-1454
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发表时间：
2017-04-01
期刊：
影响因子：
11.2
通讯作者：
Piccirilli JA
中科院分区：
文献类型：
--
作者：
Sundaram KM;Zhang Y;Mitra AK;Kouadio JK;Gwin K;Kossiakoff AA;Roman BB;Lengyel E;Piccirilli JA
卵巢癌（OvCa）是最致命的妇科恶性肿瘤，其预后不良反映了与检测和诊断相关的主要局限性。目前的方法缺乏检测小肿瘤的高灵敏度和区分恶性与良性组织的高特异性，这两者都阻碍了早期和转移性癌症阶段的诊断，并导致昂贵和侵入性手术。组织微阵列分析显示，>98%的OvCa表达催乳素受体（PRLR），这为新的分子成像策略奠定了基础。我们融合人胎盘催乳素（hPL），一个特定的和紧密结合的PRLR配体，磁共振成像（钆）和近红外荧光成像剂。在组织培养和小鼠模型中，这些成像生物缀合物通过PRLR介导的内吞作用选择性内化到OvCa细胞中。与目前的临床磁共振成像技术相比，这种靶向方法通过选择性内化积累的信号产生了增强的信噪比，并提高了恶性OvCa中PRLR上调所赋予的特异性。这些特征赋予PRLR靶向成像改变OvCa检测的潜力。
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.