It is well established that metastatic tumor cells are present in blood and bone marrow throughout the course of cancer disease (1-4). These circulating tumor cells (CTCs) are thought to seed the disease and distant metastases in the body (5,6). Isolating and characterizing the CTCs could provide invaluable information for diagnosis, treatment and prognosis of different stages of cancer (2,3,7). The concentration of CTCs in blood is typically low and can be as low as 1 cell/ml of blood (8). An ideal isolation technique has to be able to specifically capture and isolate single CTCs from billions of blood cells with close to 100% efficiency, without significant contamination by non-specific cells. We propose to use targeted microbubbles (hereafter ?bubbles) to develop a method for isolation and analysis of rare tumor cells. ?Bubbles could offer potential advantages over magnetic beads as a cell isolation technique. We show in our preliminary data that targeted ?bubbles efficiently attach to their target cells in blood, so that the cells become buoyant and easily separate from all other cells using gravity/centrifugation. The goal of this proposal is to test whether the ?bubble separation can achieve the sensitivity of magnetic bead separation, but with higher specificity, speed and productivity (ability to process >10 ml blood). These goals are achievable within the time frame of this award to allow us to assess whether further development is warranted.

Public Health Relevance

To develop and to test tumor cell isolation technique for diagnosis of cancer. The technique will be based on the use of gas microbubbles that will attach to metastatic tumor cells in blood sample and will separate by buoyancy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA137721-01
Application #
7586521
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (O1))
Program Officer
Rasooly, Avraham
Project Start
2009-06-01
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
1
Fiscal Year
2009
Total Cost
$163,249
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Shi, Guixin; Mukthavaram, Rajesh; Kesari, Santosh et al. (2014) Distearoyl anchor-painted erythrocytes with prolonged ligand retention and circulation properties in vivo. Adv Healthc Mater 3:142-8
Shi, Guixin; Cui, Wenjin; Mukthavaram, Rajesh et al. (2013) Binding and isolation of tumor cells in biological media with perfluorocarbon microbubbles. Methods 64:102-7
Shi, Guixin; Cui, Wenjin; Benchimol, Michael et al. (2013) Isolation of rare tumor cells from blood cells with buoyant immuno-microbubbles. PLoS One 8:e58017
Chao, Ying; Karmali, Priya P; Mukthavaram, Rajesh et al. (2013) Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI. ACS Nano 7:4289-98
Chao, Ying; Makale, Milan; Karmali, Priya Prakash et al. (2012) Recognition of dextran-superparamagnetic iron oxide nanoparticle conjugates (Feridex) via macrophage scavenger receptor charged domains. Bioconjug Chem 23:1003-9
Karmali, Priya Prakash; Chao, Ying; Park, Ji-Ho et al. (2012) Different effect of hydrogelation on antifouling and circulation properties of dextran-iron oxide nanoparticles. Mol Pharm 9:539-45