title: Detection and quantitation of circulating tumor cell dynamics by bioluminescence imaging in an orthotopic mammary carcinoma model.
abstract: Circulating tumor cells (CTCs) have been detected in the bloodstream of both early-stage and advanced cancer patients. However, very little is know about the dynamics of CTCs during cancer progression and the clinical relevance of longitudinal CTC enumeration. To address this, we developed a simple bioluminescence imaging assay to detect CTCs in mouse models of metastasis. In a 4T1 orthotopic metastatic mammary carcinoma mouse model, we demonstrated that this quantitative method offers sensitivity down to 2 CTCs in 0.1-1mL blood samples and high specificity for CTCs originating from the primary tumor, independently of their epithelial status. In this model, we simultaneously monitored blood CTC dynamics, primary tumor growth, and lung metastasis progression over the course of 24 days. Early in tumor development, we observed low numbers of CTCs in blood samples (10-15 cells/100 µL) and demonstrated that CTC dynamics correlate with viable primary tumor growth. To our knowledge, these data represent the first reported use of bioluminescence imaging to detect CTCs and quantify their dynamics in any cancer mouse model. This new assay is opening the door to the study of CTC dynamics in a variety of animal models. These studies may inform clinical decision on the appropriate timing of blood sampling and value of longitudinal CTC enumeration in cancer patients.
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California, United States of America; Department of Bioengineering, Stanford University, Stanford, California, United States of America.
authors.forename: Laura Sarah
authors.initials: LS
authors.lastname: Sasportas
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Sharon Seiko
authors.initials: SS
authors.lastname: Hori
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, California, United States of America.
authors.forename: Guillem
authors.initials: G
authors.lastname: Pratx
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Sanjiv Sam
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006461:Hemolysis; D008163:Luminescent Measurements / Q000379:methods*; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000097:blood* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*