title: Imaging of Her2-targeted magnetic nanoparticles for breast cancer detection: comparison of SQUID-detected magnetic relaxometry and MRI.
abstract: Both magnetic relaxometry and magnetic resonance imaging (MRI) can be used to detect and locate targeted magnetic nanoparticles, noninvasively and without ionizing radiation. Magnetic relaxometry offers advantages in terms of its specificity (only nanoparticles are detected) and the linear dependence of the relaxometry signal on the number of nanoparticles present. In this study, detection of single-core iron oxide nanoparticles by superconducting quantum interference device (SQUID)-detected magnetic relaxometry and standard 4.7 T MRI are compared. The nanoparticles were conjugated to a Her2 monoclonal antibody and targeted to Her2-expressing MCF7/Her2-18 (breast cancer cells); binding of the nanoparticles to the cells was assessed by magnetic relaxometry and iron assay. The same nanoparticle-labeled cells, serially diluted, were used to assess the detection limits and MR relaxivities. The detection limit of magnetic relaxometry was 125 000 nanoparticle-labeled cells at 3 cm from the SQUID sensors. T(2)-weighted MRI yielded a detection limit of 15 600 cells in a 150 µl volume, with r(1) = 1.1 mm(-1) s(-1) and r(2) = 166 mm(-1) s(-1). Her2-targeted nanoparticles were directly injected into xenograft MCF7/Her2-18 tumors in nude mice, and magnetic relaxometry imaging and 4.7 T MRI were performed, enabling direct comparison of the two techniques. Co-registration of relaxometry images and MRI of mice resulted in good agreement. A method for obtaining accurate quantification of microgram quantities of iron in the tumors and liver by relaxometry was also demonstrated. These results demonstrate the potential of SQUID-detected magnetic relaxometry imaging for the specific detection of breast cancer and the monitoring of magnetic nanoparticle-based therapies.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. NAdolphi@salud.unm.edu
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Adolphi
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Butler
authors.forename: Debbie M
authors.initials: DM
authors.lastname: Lovato
authors.forename: T E
authors.initials: TE
authors.lastname: Tessier
authors.forename: Jason E
authors.initials: JE
authors.lastname: Trujillo
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Hathaway
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Fegan
authors.forename: Todd C
authors.initials: TC
authors.lastname: Monson
authors.forename: Tyler E
authors.initials: TE
authors.lastname: Stevens
authors.forename: Dale L
authors.initials: DL
authors.lastname: Huber
authors.forename: Jaivijay
authors.initials: J
authors.lastname: Ramu
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Milne
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Altobelli
authors.forename: Howard C
authors.initials: HC
authors.lastname: Bryant
authors.forename: Richard S
authors.initials: RS
authors.lastname: Larson
authors.forename: Edward R
authors.initials: ER
authors.lastname: Flynn
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D005290:Ferric Compounds; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D051379:Mice; D057054:Molecular Imaging; D011789:Quantum Theory; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D012031:Refractometry / Q000295:instrumentation*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D018719:Erb-b2 Receptor Tyrosine Kinases; C000499:ferric oxide