The early detection of ovarian cancer (OvCa) is a challenge because the postmenopausal ovaries are hidden in the peritoneal cavity and current imaging technologies lack the ability to differentiate between benign and malignant masses. Our goal is to improve the detection and imaging of OvCa utilizing cancer cell-targeted, bimodal fluorescent and paramagnetic micelles that effectively detect malignant tumors. The human prolactin receptor (PrlR) is expressed in 98% of malignant ovarian tumors, but is not expressed in benign ovarian tumors or fallopian tubes. Therefore, we conjugated the maleimide-functional micelles to a thiol group of human placental lactogen (hPL), a ligand of PrlR, to specifically target OvCa cells. The micelles were 20-nm in diameter with a favorable surface charge (-5.8mV) characterized by dynamic light scattering, zeta potential, and transmission electron microscopy (TEM). After conjugation to hPL, hPL-micelles displayed an increased molecular weight and particle size as assessed by SDS-PAGE, MALDI-TOF, and size exclusion chromatography. Microscopic and cytometric analyses demonstrated that hPL-micelles were more efficiently internalized in human primary OvCa cells and OvCa cell lines than unconjugated micelles. The knockdown of PrlR using shRNA in OvCa cell lines or the triple mutation of hPL significantly inhibited uptake of hPL-fluorophore conjugates, suggesting receptor-mediated endocytosis. Furthermore, the Xenogen IVIS small animal imaging system detected a greater accumulation of hPL-micelles than of unconjugated micelles in the human ovarian tumor xenograft, confirming the enhanced imaging of OvCa through targeted delivery. Given the low prevalence of OvCa and the current unsatisfactory imaging modalities, “receptor-dependent imaging” through hPL-decorated bimodal micelles has the potential to improve detection of OvCa through enhanced specificity.

Citation Format: Yilin Zhang, Karthik M. Sundaram, Nan-Sheng Li, Joseph A. Piccirilli, Ernst Lengyel. Human placental lactogen-functionalized bimodal imaging probe for human ovarian cancer detection [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-CTRL-1217.

©2015 American Association for Cancer Research.
2015