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

TitleProlactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity.
Publication TypeJournal Article
Year of Publication2017
AuthorsSundaram, Karthik M., Zhang Yilin, Mitra Anirban K., Kouadio Jean-Louis K., Gwin Katja, Kossiakoff Anthony A., Roman Brian B., Lengyel Ernst, and Piccirilli Joseph A.
JournalCancer Res
Volume77
Issue7
Pagination1684-1696
Date Published2017 Apr 01
ISSN1538-7445
KeywordsAnimals, Cell Line, Tumor, Endocytosis, Female, Gadolinium DTPA, Humans, Magnetic Resonance Imaging, Mice, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Placental Lactogen, Prolactin, Receptors, Prolactin, Sensitivity and Specificity, Tissue Array Analysis
Abstract

<p>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.</p>

DOI10.1158/0008-5472.CAN-16-1454
Alternate JournalCancer Res.
PubMed ID28202518
PubMed Central IDPMC5380561
Grant ListR01 CA111882 / CA / NCI NIH HHS / United States
R01 GM088656 / GM / NIGMS NIH HHS / United States

University of Toronto  UCSF  The University of Chicago  QB3  Chicago Biomedical Consortium