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Investigation of In Vivo Targeting Kinetics of αvβ3-Specific Superparamagnetic Nanoprobes by Time-Resolved MRI

By Chase W. Kessinger, Osamu Togao, Chalermchai Khemtong, Gang Huang, Masaya Takahashi and Jinming Gao


Nanoparticulate imaging probes have become an increasingly important arsenal in the visualization of molecular markers for early diagnosis and post-therapy assessment of diseases. Surface functionalization of these nanoparticles has led to the development of a variety of targeted nanoprobes for various imaging modalities (e.g. PET, MRI, optical). Despite these advances, detailed understanding of the nanoparticle targeting kinetics, particularly at the early time points immediately after injection, is still lacking. In this study, we report the combination of a T2*-weighted time-resolved-MRI (TR-MRI) method with ultra-sensitive superparamagnetic polymeric micelle (SPPM) nanoprobes to quantify the targeting kinetics of cyclic (RGDfK) (cRGD)-encoded SPPM to angiogenic endothelium in subcutaneous human tumor xenograft models in mice. TR-MRI analyses of the αvβ3-targeted and non-targeted SPPMs allowed for the subtraction of blood volume and extravascular signal components from the cRGD-SPPM data, resulting in a specific measurement of the accumulation kinetics of nanoprobes in lung, breast and brain cancer preclinical models. In all three models, αvβ3-specific accumulation of SPPM nanoprobes was observed in the first 5 mins after intravenous injection (first order rate constants were in the range of 0.22-0.24 min-1). Similar αvβ3-targeting kinetics was observed for cRGD-SPPM nanoprobes in different tumor xenograft models, consistent with the targeting of mouse angiogenic endothelium despite tumor inoculation from different human cancer cell lines. Results from this study offer new opportunities in the quantitative characterization of the targeting kinetics of cancer-specific nanoparticles to their intended biological targets in an intact animal, which provides fundamental insights on molecular recognition processes in vivo for further development of these nanoprobes

Topics: Research Paper
Publisher: Ivyspring International Publisher
OAI identifier:
Provided by: PubMed Central

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  1. (1998). A model for MRI contrast enhancement using T1 agents.
  2. A reexamination of active and passive tumor targeting by using rod-shaped gold nanocrystals and covalently conjugated peptide ligands.
  3. (2006). Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res.
  4. (2007). Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat Med.
  5. (2002). Cellular internalization of poly(ethylene oxide)-b-poly(epsilon-caprolactone) diblock copolymer micelles. Bioconjug Chem.
  6. (1999). Characterization of N-ethyl-N-nitrosourea-induced malignant and benign breast tumors in rats by using three MR contrast agents. J Magn Reson Imaging.
  7. (2007). DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents.
  8. (1999). Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging.
  9. (2006). FeCo/graphitic-shell nanocrystals as advanced magnetic-resonance-imaging and near-infrared agents. Nat Mater.
  10. (2005). Folate-conjugated iron oxide nanoparticles for solid tumor targeting as potential specific magnetic hyperthermia mediators: synthesis, physicochemical characterization, and in vitro experiments. Bioconjug Chem.
  11. (2010). In vivo angiogenesis imaging of solid tumors by alpha(v)beta(3)-targeted, dual-modality micellar nanoprobes. Exp Biol Med (Maywood).
  12. (2009). In vivo off-resonance saturation magnetic resonance imaging of alphavbeta3-targeted superparamagnetic nanoparticles. Cancer Res.
  13. (2004). Iron oxide MR contrast agents for molecular and cellular imaging. Nmr Biomed.
  14. (2005). Magnetite-loaded polymeric micelles as ultrasensitive magnetic resonance probes. Adv Mater.
  15. (2005). MR molecular imaging and fluorescence microscopy for identification of activated tumor endothelium using a bimodal lipidic nanoparticle.
  16. (2003). MR molecular imaging of the Her-2/neu receptor in breast cancer cells using targeted iron oxide nanoparticles. Magn Reson Med.
  17. (2006). Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett.
  18. (2008). Multimodality molecular imaging of tumor angiogenesis.
  19. (2007). Nanotechnology applications in cancer. Annual Review of Biomedical Engineering.
  20. (1990). Perfusion imaging with NMR contrast agents. Magn Reson Med.
  21. (2009). Polymeric nanomedicine for cancer MR imaging and drug delivery. Chem Commun (Camb).
  22. (2006). Quantification of the expression level of integrin receptor alpha(v)beta3 in cell lines and MR imaging with antibody-coated iron oxide particles. Magn Reson Med.
  23. (2006). Recent advances in iron oxide nanocrystal technology for medical imaging. Advanced Drug Delivery Reviews.
  24. (2002). Size-controlled synthesis of magnetite nanoparticles.
  25. (2007). Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. Cancer Res.
  26. (2006). Superparamagnetic iron oxide nanoparticle probes for molecular imaging. Ann Biomed Eng.
  27. (2008). Synergistically Integrated Nanoparticles as Multimodal Probes for Nanobiotechnology. Accounts of Chemical Research.
  28. The transferrin receptor: a potential molecular imaging marker for human cancer.
  29. (2007). Theoretical MRI contrast model for exogenous T2 agents. Magn Reson Med.
  30. (2008). Three-dimensional MR mapping of angiogenesis with alpha5beta1(alpha nu beta3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model.
  31. (2008). Zinc ferrite nanoparticles as MRI contrast agents. Chem Commun (Camb).

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