Bisphosphonate-anchored pegylation and radiolabeling of superparamagnetic iron oxide: Long-circulating nanoparticles for in vivo multimodal (T1 MRI-SPECT) imaging

  • Sandiford L
  • Phinikaridou A
  • Protti A
 et al. 
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Abstract

The efficient delivery of nanomaterials to specific targets for in vivo biomedical imaging is hindered by rapid sequestration by the reticuloendothelial system (RES) and consequent short circulation times. To overcome these two problems, we have prepared a new stealth PEG polymer conjugate containing a terminal 1,1-bisphosphonate (BP) group for strong and stable binding to the surface of ultrasmall-superparamagnetic oxide nanomaterials (USPIOs). This polymer, PEG(5)-BP, can be used to exchange the hydrophobic surfactants commonly used in the synthesis of USPIOs very efficiently and at room temperature using a simple method in 1 h. The resulting nanoparticles, PEG(5)-BP-USPIOs are stable in water or saline for at least 7 months and display a near-zero ζ-potential at neutral pH. The longitudinal (r(1)) and transverse (r(2)) relaxivities were measured at a clinically relevant magnetic field (3 T), revealing a high r(1) of 9.5 mM(-1) s(-1) and low r(2)/r(1) ratio of 2.97, making these USPIOs attractive as T1-weighted MRI contrast agents at high magnetic fields. The strong T1-effect was demonstrated in vivo, revealing that PEG(5)-BP-USPIOs remain in the bloodstream and enhance its signal 6-fold, allowing the visualization of blood vessels and vascular organs with high spatial definition. Furthermore, the optimal relaxivity properties allow us to inject a dose 4 times lower than with other USPIOs. PEG(5)-BP-USPIOs can also be labeled using a radiolabeled-BP for visualization with single photon emission computed tomography (SPECT), and thus affording dual-modality contrast. The SPECT studies confirmed low RES uptake and long blood circulation times (t(1/2) = 2.97 h). These results demonstrate the potential of PEG(5)-BP-USPIOs for the development of targeted multimodal imaging agents for molecular imaging.

Author-supplied keywords

  • MRI
  • PEG
  • RES
  • SPECT
  • USPIO
  • bisphosphonates
  • multimodal imaging
  • superparamagnetic iron oxide

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Authors

  • Lydia Sandiford

  • Alkystis Phinikaridou

  • Andrea Protti

  • Levente K. Meszaros

  • Xianjin Cui

  • Yong Yan

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