title: A strategy for blood biomarker amplification and localization using ultrasound.
abstract: Blood biomarkers have significant potential applications in early detection and management of various diseases, including cancer. Most biomarkers are present in low concentrations in blood and are difficult to discriminate from noise. Furthermore, blood measurements of a biomarker do not provide information about the location(s) where it is produced. We hypothesize a previously undescribed strategy to increase the concentration of biomarkers in blood as well as localize the source of biomarker signal using ultrasound energy directly applied to tumor cells. We test and validate our hypothesis in cell culture experiments and mouse tumor xenograft models using the human colon cancer cell line LS174T, while measuring the biomarker carcinoembryonic antigen (CEA) before and after the use of ultrasound to liberate the biomarker from the tumor cells. The results demonstrate that the application of low-frequency ultrasound to tumor cells causes a significant release of tumor biomarker, which can be measured in the blood. Furthermore, we establish that this release is specific to the direct application of the ultrasound to the tumor, enabling a method for localization of biomarker production. This work shows that it is possible to use ultrasound to amplify and localize the source of CEA levels in blood of tumor-bearing mice and will allow for a previously undescribed way to determine the presence and localization of disease more accurately using a relatively simple and noninvasive strategy.
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Aloma L
authors.initials: AL
authors.lastname: D'Souza
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Tseng
authors.forename: Kim Butts
authors.initials: KB
authors.lastname: Pauly
authors.forename: Samira
authors.initials: S
authors.lastname: Guccione
authors.forename: Jarrett
authors.initials: J
authors.lastname: Rosenberg
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: Gary M
authors.initials: GM
authors.lastname: Glazer
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000097:blood*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis / Q000097:blood / Q000378:metabolism / Q000473:pathology; D009374:Neoplasms, Experimental / Q000097:blood / Q000175:diagnosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014183:Transplantation, Heterologous; D014465:Ultrasonics
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen