title: Preclinical studies of the role of iron oxide magnetic nanoparticles for nonpalpable lesion localization in breast cancer.
abstract: BACKGROUND
  One-third of all breast cancers are present as clinically nonpalpable lesions. The current gold standard treatment is surgical excision by wire-guided localization. This technique has patient, technical, and scheduling drawbacks. Alternatives exist but depend on radioisotopes with their legislative and waste management issues. Magnetic nanoparticles (MNPs) have already been successfully used for sentinel lymph node biopsy in breast cancer. We therefore aimed to determine the feasibility of using iron oxide MNPs and a handheld magnetometer for the localization of nonpalpable breast cancers using a preclinical model.
  
  
  METHODS
  We constructed phantom models to assess the relationship between the handheld magnetometer peak readings and the variation in volume of iron oxide MNPs and their depth of injection in a series of porcine and avian tissue models. We also radiolabeled the MNPs with (99m)Tc and alendronate to create the conjugate (99m)Tc-dipicolylamine-alendronate-MNP and used nano-single-photon emission computed tomography-computed tomography to perform imaging to demonstrate localization properties.
  
  
  RESULTS
  The handheld magnetometer readings follow a linear relationship with variations in volume of magnetic tracer and a logarithmic relationship with variations in depth of injection of the magnetic tracer at a fixed volume. The application of derived quadratic equations from the R(2) curves of handheld magnetometer signal versus depth allowed calculation of the depth of injection of iron oxide MNPs from the handheld magnetometer readings and demonstrated the predictable behavior of the iron oxide MNPs and the handheld magnetometer. Satisfactory localization characteristics were confirmed in the phantoms and imaged using nano-single-photon emission computed tomography and computed tomography.
  
  
  CONCLUSIONS
  Iron oxide MNPs demonstrate positive localization characteristics in phantom models with predictable behavior patterns. We suggest that the use of MNPs provides a potential technique for the localization of nonpalpable breast lesions and deserves further exploration in animal and human feasibility studies.
authors.affiliation: Department of Research Oncology, King's College London, Guy's Hospital Campus, London, UK.
authors.forename: Muneer
authors.initials: M
authors.lastname: Ahmed
authors.forename: Rafael Torres Martin
authors.initials: RT
authors.lastname: de Rosales
authors.forename: Michael
authors.initials: M
authors.lastname: Douek
mesh_terms: D019386:Alendronate; D000588:Amines; D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery*; D002645:Chickens; D005240:Feasibility Studies; D005260:Female; D005290:Ferric Compounds; D060526:Magnetic Fields; D053768:Metal Nanoparticles; D023421:Models, Animal; D015609:Organotechnetium Compounds; D019047:Phantoms, Imaging; D010848:Picolinic Acids; D019275:Radiopharmaceuticals; D013552:Swine; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: C501847:2,2'-dipicolylamine; D000588:Amines; D005290:Ferric Compounds; D015609:Organotechnetium Compounds; D010848:Picolinic Acids; D019275:Radiopharmaceuticals; C000499:ferric oxide; D019386:Alendronate
keywords: Breast cancer; Magnetic nanoparticles; Nonpalpable lesion localization