Detection of breast cancer cells using targeted magnetic nanoparticles and ultra-sensitive magnetic field sensors

Journal Article · Sat Oct 01 00:00:00 EDT 2011 · Breast Cancer Research

DOI:https://doi.org/10.1186/bcr3050· OSTI ID:1626697

Hathaway, Helen J. ^[1]; Butler, Kimberly S. ^[2]; Adolphi, Natalie L. ^[3]; Lovato, Debbie M. ^[2]; Belfon, Robert ^[4]; Fegan, Danielle ^[5]; Monson, Todd C. ^[6]; Trujillo, Jason E. ^[7]; Tessier, Trace E. ^[5]; Bryant, Howard C. ^[5]; Huber, Dale L. ^[8]; Larson, Richard S. ^[9]; Flynn, Edward R. ^[10]

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1. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Cell Biology and Physiology; Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Cancer Research and Treatment Center; DOE/OSTI
2. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Pathology
3. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Cancer Research and Treatment Center; Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Biochemistry and Molecular Biology
4. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Cell Biology and Physiology
5. Senior Scientific LLC, Albuquerque, NM (United States)
6. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Nanomaterials Sciences Dept.
7. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Pathology; Senior Scientific LLC, Albuquerque, NM (United States)
8. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Center for Integrated Nanotechnologies
9. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Cancer Research and Treatment Center; Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Dept. of Pathology
10. Univ. of New Mexico, Albuquerque, NM (United States). School of Medicine. Cancer Research and Treatment Center; Senior Scientific LLC, Albuquerque, NM (United States)

Introduction: Breast cancer detection using mammography has improved clinical outcomes for many women, because mammography can detect very small (5 mm) tumors early in the course of the disease. However, mammography fails to detect 10 - 25% of tumors, and the results do not distinguish benign and malignant tumors. Reducing the false positive rate, even by a modest 10%, while improving the sensitivity, will lead to improved screening, and is a desirable and attainable goal. The emerging application of magnetic relaxometry, in particular using superconducting quantum interference device (SQUID) sensors, is fast and potentially more specific than mammography because it is designed to detect tumor-targeted iron oxide magnetic nanoparticles. Furthermore, magnetic relaxometry is theoretically more specific than MRI detection, because only target-bound nanoparticles are detected. Our group is developing antibody-conjugated magnetic nanoparticles targeted to breast cancer cells that can be detected using magnetic relaxometry. Methods: To accomplish this, we identified a series of breast cancer cell lines expressing varying levels of the plasma membrane-expressed human epidermal growth factor-like receptor 2 (Her2) by flow cytometry. Anti-Her2 antibody was then conjugated to superparamagnetic iron oxide nanoparticles using the carbodiimide method. Labeled nanoparticles were incubated with breast cancer cell lines and visualized by confocal microscopy, Prussian blue histochemistry, and magnetic relaxometry. Results: We demonstrated a time- and antigen concentration-dependent increase in the number of antibodyconjugated nanoparticles bound to cells. Next, anti Her2-conjugated nanoparticles injected into highly Her2- expressing tumor xenograft explants yielded a significantly higher SQUID relaxometry signal relative to unconjugated nanoparticles. Finally, labeled cells introduced into breast phantoms were measured by magnetic relaxometry, and as few as 1 million labeled cells were detected at a distance of 4.5 cm using our early prototype system. Conclusions: These results suggest that the antibody-conjugated magnetic nanoparticles are promising reagents to apply to in vivo breast tumor cell detection, and that SQUID-detected magnetic relaxometry is a viable, rapid, and highly sensitive method for in vitro nanoparticle development and eventual in vivo tumor detection.

• Research Organization: Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
• Grant/Contract Number: AC04-94AL85000
• OSTI ID: 1626697
• Journal Information: Breast Cancer Research, Journal Name: Breast Cancer Research Journal Issue: 5 Vol. 13; ISSN 1465-542X
• Publisher: BioMed Central
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
Oncology