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Cancer Res. 2017 Apr 1;77(7):1684-1696. doi: 10.1158/0008-5472.CAN-16-1454. Epub 2017 Feb 15.

Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity.

Author information

1
Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois.
2
Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois.
3
Department of Pathology, The University of Chicago, Chicago, Illinois.
4
Department of Radiology, The University of Chicago, Chicago, Illinois.
5
Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois. elengyel@uchicago.edu jpicciri@uchicago.edu.
6
Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois. elengyel@uchicago.edu jpicciri@uchicago.edu.

Abstract

Poor prognosis of ovarian cancer, 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 ovarian cancers 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 ovarian cancer cells via PRLR-mediated endocytosis. Compared with current clinical MRI 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 ovarian cancer. These features endow PRLR-targeted imaging with the potential to transform ovarian cancer detection. Cancer Res; 77(7); 1684-96. ©2017 AACR.

PMID:
28202518
PMCID:
PMC5380561
DOI:
10.1158/0008-5472.CAN-16-1454
[Indexed for MEDLINE]
Free PMC Article

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