TY - JOUR
T1 - Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer with enhanced sensitivity and specificity
AU - Sundaram, Karthik M.
AU - Zhang, Yilin
AU - Mitra, Anirban K.
AU - Kouadio, Jean Louis K.
AU - Gwin, Katja
AU - Kossiakoff, Anthony A.
AU - Roman, Brian B.
AU - Lengyel, Ernst
AU - Piccirilli, Joseph A.
N1 - Funding Information:
This work was supported in part by the Medical Scientist Training Program (K.M. Sundaram), Howard Hughes Medical Institute (J.A. Piccirilli), Woman's Board Grant (E. Lengyel and J.A. Piccirilli), Burroughs Wellcome Fund (E. Lengyel), Noreen Fraser Foundation (E. Lengyel), Ovarian Cancer Research Fund (E. Lengyel), NIH Grant R01GM088656 (J.A. Piccirilli), and the BSD Imaging Research Institute Pilot Grants (J.A. Piccirilli, E. Lengyel, and B.R. Roman).
Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-16-1454
DO - 10.1158/0008-5472.CAN-16-1454
M3 - Article
C2 - 28202518
AN - SCOPUS:85017404934
SN - 0008-5472
VL - 77
SP - 1684
EP - 1696
JO - Cancer research
JF - Cancer research
IS - 7
ER -