title: Preclinical evaluation of Mab CC188 for ovarian cancer imaging.
abstract: Cancer stem cells (CSCs) have been successfully isolated from solid tumors and are believed to be initiating cells of primary, metastatic and recurrent tumors. Imaging and therapeutic reagents targeted to CSCs have potential to detect subclinical tumors and completely eradicate the disease. Previously, we have demonstrated that Mab CC188 binds to colon cancer CD133- and CD133+ (CSCs) cells. In this study, we examined the reactivity of Mab CC188 to ovarian cancer cells including CD133+ cells and primary tumor tissues using immunofluorescence staining methods and tissue microarray technique. We also explored the feasibility of using NIR dye-labeled Mab CC188 probe to image ovarian tumors in vivo. Mab CC188 stains both CD133- and CD133+ cells of ovarian cancer. Tissue microarray analysis reveals that 75% (92/123) of ovarian cancer cases are positively stained with Mab CC188. Weak positive (±), positive (+), strong positive (++) and very strong positive (+++) stains are 14.8, 3.7, 11 and 24.4%, respectively. In contrast, Mab CC188 staining is low in normal cells and tissues. In vivo study show that significant amounts of the probe accumulates in the excretion organs in the early period postinjection. At 24 hr, the imaging probes have largely accumulates in the tumor, while the intensity of the imaging probe decreases in the liver. The tumor uptake was still evident at 120-hr postinjection. Our work suggests that Mab CC188-based imaging and therapeutic reagents are capable of detecting early stage ovarian tumors and effectively treating the tumor.
authors: Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA. xum@mir.wustl.edu
authors: M
authors: M
authors: Xu
authors: M P
authors: MP
authors: Rettig
authors: G
authors: G
authors: Sudlow
authors: B
authors: B
authors: Wang
authors: W J
authors: WJ
authors: Akers
authors: D
authors: D
authors: Cao
authors: D G
authors: DG
authors: Mutch
authors: J F
authors: JF
authors: DiPersio
authors: S
authors: S
authors: Achilefu
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D045744:Cell Line, Tumor; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology; D010455:Peptides / Q000032:analysis*; D046888:Tissue Array Analysis
chemical_list: D000071916:AC133 Antigen; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse