title: Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity.
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.
authors.affiliation: Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois.
authors.forename: Karthik M
authors.initials: KM
authors.lastname: Sundaram
authors.affiliation: Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois.
authors.forename: Anirban K
authors.initials: AK
authors.lastname: Mitra
authors.affiliation: Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois.
authors.forename: Jean-Louis K
authors.initials: JK
authors.lastname: Kouadio
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois.
authors.forename: Katja
authors.initials: K
authors.lastname: Gwin
authors.affiliation: Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois.
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Kossiakoff
authors.affiliation: Department of Radiology, The University of Chicago, Chicago, Illinois.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Roman
authors.affiliation: Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois. elengyel@uchicago.edu jpicciri@uchicago.edu.
authors.forename: Ernst
authors.initials: E
authors.lastname: Lengyel
authors.affiliation: Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois. elengyel@uchicago.edu jpicciri@uchicago.edu.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Piccirilli
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D004705:Endocytosis; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000000981:diagnostic imaging* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D010928:Placental Lactogen / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D011981:Receptors, Prolactin / Q000032:analysis / Q000502:physiology*; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis
chemical_list: D011981:Receptors, Prolactin; D011388:Prolactin; D010928:Placental Lactogen; D019786:Gadolinium DTPA