Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer with enhanced sensitivity and specificity

Karthik M. Sundaram, Yilin Zhang, Anirban Mitra, Jean Louis K. Kouadio, Katja Gwin, Anthony A. Kossiakoff, Brian B. Roman, Ernst Lengyel, Joseph A. Piccirilli

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1684-1696
Number of pages13
JournalCancer Research
Volume77
Issue number7
DOIs
StatePublished - 2017
Externally publishedYes

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Prolactin Receptors
Ovarian Neoplasms
Sensitivity and Specificity
Tissue Array Analysis
Placental Lactogen
Molecular Imaging
Optical Imaging
Gadolinium
Signal-To-Noise Ratio
Endocytosis
Fluorescent Dyes
Early Detection of Cancer
Neoplasms
Up-Regulation
Magnetic Resonance Imaging
Ovarian epithelial cancer
Ligands

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer with enhanced sensitivity and specificity. / Sundaram, Karthik M.; Zhang, Yilin; Mitra, Anirban; Kouadio, Jean Louis K.; Gwin, Katja; Kossiakoff, Anthony A.; Roman, Brian B.; Lengyel, Ernst; Piccirilli, Joseph A.

In: Cancer Research, Vol. 77, No. 7, 2017, p. 1684-1696.

Research output: Contribution to journalArticle

Sundaram, KM, Zhang, Y, Mitra, A, Kouadio, JLK, Gwin, K, Kossiakoff, AA, Roman, BB, Lengyel, E & Piccirilli, JA 2017, 'Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer with enhanced sensitivity and specificity', Cancer Research, vol. 77, no. 7, pp. 1684-1696. https://doi.org/10.1158/0008-5472.CAN-16-1454
Sundaram, Karthik M. ; Zhang, Yilin ; Mitra, Anirban ; Kouadio, Jean Louis K. ; Gwin, Katja ; Kossiakoff, Anthony A. ; Roman, Brian B. ; Lengyel, Ernst ; Piccirilli, Joseph A. / Prolactin receptor-mediated internalization of imaging agents detects epithelial ovarian cancer with enhanced sensitivity and specificity. In: Cancer Research. 2017 ; Vol. 77, No. 7. pp. 1684-1696.
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