title: Micro-CT enables microlocalisation and quantification of Her2-targeted gold nanoparticles within tumour regions.
abstract: OBJECTIVE
  Gold nanoparticles are of interest as potential in vivo diagnostic and therapeutic agents, as X-ray contrast agents, drug delivery vehicles and radiation enhancers. The aim of this study was to quantitatively determine their targeting and microlocalisation in mouse tumour models after intravenous injection by using micro-CT.
  
  
  METHODS
  Gold nanoparticles (15 nm) were coated with polyethylene glycol and covalently coupled to anti-Her2 antibodies (Herceptin). In vitro, conjugates incubated with Her2+ (BT-474) and Her2- (MCF7) human breast cancer cells showed specific targeted binding with a Her2+ to Her2- gold ratio of 39.4±2.7:1. Nude mice, simultaneously bearing subcutaneous Her2+ and Her2- human breast tumours in opposite thighs were prepared. Gold nanoparticles alone, conjugated to Herceptin or to a non-specific antibody were compared. After intravenous injection of the gold nanoparticles, gold concentrations were determined by atomic absorption spectroscopy. Microlocalisation of gold was carried out by calibrated micro-CT, giving both the radiodensities and gold concentrations in tumour and non-tumour tissue.
  
  
  RESULTS
  All gold nanoparticle constructs showed accumulation, predominantly at tumour peripheries. However, the Herceptin-gold nanoparticles showed the best specific uptake in their periphery (15.8±1.7% injected dose per gram), 1.6-fold higher than Her2- tumours and 22-fold higher than surrounding muscle. Imaging readily enabled detection of small, 1.5 mm-thick tumours.
  
  
  CONCLUSIONS
  In this pre-clinical study, antibody-targeted 15 nm gold nanoparticles showed preferential uptake in cognate tumours, but even untargeted gold nanoparticles enhanced the visibility of tumour peripheries and enabled detection of millimetre-sized tumours. Micro-CT enabled quantification within various regions of a tumour.
authors.affiliation: Nanoprobes, Inc., 95 Horseblock Road, Yaphank, NY 11980, USA. hainfeld@nanoprobes.com
authors.forename: J F
authors.initials: JF
authors.lastname: Hainfeld
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connor
authors.forename: F A
authors.initials: FA
authors.lastname: Dilmanian
authors.forename: D N
authors.initials: DN
authors.lastname: Slatkin
authors.forename: D J
authors.initials: DJ
authors.lastname: Adams
authors.forename: H M
authors.initials: HM
authors.lastname: Smilowitz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D045744:Cell Line, Tumor / Q000473:pathology*; D003287:Contrast Media / Q000493:pharmacokinetics; D004337:Drug Carriers; D005260:Female; D006046:Gold / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage; D000068878:Trastuzumab; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D004337:Drug Carriers; D006046:Gold; D000068878:Trastuzumab