Abstract
The Follicle-Stimulating Hormone Receptor (FSHR) is used as an imaging biomarker for the detection of ovarian cancer (OC). FSHR is highly expressed on ovarian tumors and involved with cancer development and metastatic signaling pathways. A decapeptide specific to the FSHR extracellular domain is synthesized and conjugated to fluorescent dyes to image OC cells in vitro and tumors xenograft model in vivo. The in vitro binding curve and the average number of FSHR per cell are obtained for OVCAR-3 cells by a high resolution flow cytometer. For the decapeptide, the measured EC50 was 160 μM and the average number of receptors per cell was 1.7 × 107. The decapeptide molecular imaging probe reached a maximum tumor to muscle ratio five hours after intravenous injection and a dose-dependent plateau after 24–48 hours. These results indicate the potential application of a small molecular weight imaging probe specific to ovarian cancer through binding to FSHR. Based on these results, multimeric constructs are being developed to optimize binding to ovarian cells and tumors.
Highlights
Ovarian cancer (OC) is the leading cause of mortality from gynecological cancer in women, with a five year survival rate less than 45% [1,2]
An important factor that could influence these results is if there is a loss of receptor function due to a significant amount of freely suspended fluorescein remaining in the buffer
Cells were visually inspected prior to and after incubation with BI-10 peptides to assure cells were attached to the plate
Summary
Ovarian cancer (OC) is the leading cause of mortality from gynecological cancer in women, with a five year survival rate less than 45% [1,2]. Due to lack of specific symptoms and reliable screening procedures, the majority of women with OC (60–65% of patients) are diagnosed late (stages III-IV) when the cancer has spread beyond the ovaries, resulting in a 5 year survival rate of 16–28% [3]. Several hypotheses to explain the etiology of ovarian epithelial cancer have been proposed, including the incessant ovulation hypothesis [4,5], the gonadotropin theory [6,7], and the sex-steroid hormones hypothesis [8,9]. Overall the molecular mechanisms of ovarian epithelial cancer tumorigenesis and metastasis remain unclear [3,10,11]. Searching novel diagnostic markers to improve early ovarian cancer detection has been an active research [12,13]
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