Imaging of Vx-2 rabbit tumors with αvβ3- integrin-targeted 111In nanoparticles

Grace Hu, Michal Lijowski, Huiying Zhang, Kathryn C. Partlow, Shelton D. Caruthers, Garry Kiefer, Gyongyi Gulyas, Phillip Athey, Michael J. Scott, Samuel A. Wickline, Gregory M. Lanza

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107 Scopus citations

Abstract

Earlier tumor detection can improve 5-year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. αvβ3-Targeted 111In nanoparticles (NP) were developed and studied for detection of tumor angiogenesis. Studies were conducted in New Zealand white rabbits implanted 12 days earlier with Vx-2 tumor. αvβ3-Targeted 111In/NP bearing ∼10 111In/NP vs. ∼1 111In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand-targeting specificity. αvβ3-Integrin-targeted NP with ∼10 111In/NP provided better (p < 0.05) tumor-to-muscle ratio contrast (6.3 ± 0.2) than ∼1 111In/NP (5.1 ± 0.1) or nontargeted particles with ∼10 111In/NP (3.7 ± 0.1) over the initial 2-hr postinjection. At 18 hr, mean tumor activity in rabbits receiving αvβ3-integrin-targeted NP was 4-fold higher than the nontargeted control. Specificity of the NP for the tumor neovasculature was supported by in vivo competition studies and by fluorescence microscopy of αvβ3-targeted fluorescent-labeled NP. Biodistribution studies revealed that the primary clearance organ in rabbits as a %ID/g tissue was the spleen. Circulatory half-life (t 1/2β) was estimated to be ∼5 hr using a 2-compartment model. αvβ3-Targeted 111In perfluorocarbon NP may provide a clinically useful tool for sensitively detecting angiogenesis in nascent tumors, particularly in combination with secondary high-resolution imaging modalities, such as MRI.

Original languageEnglish
Pages (from-to)1951-1957
Number of pages7
JournalInternational Journal of Cancer
Volume120
Issue number9
DOIs
StatePublished - May 1 2007

Keywords

  • Angiogenesis
  • Cancer
  • Indium
  • Integrin
  • Nanoparticles
  • Vx2

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    Hu, G., Lijowski, M., Zhang, H., Partlow, K. C., Caruthers, S. D., Kiefer, G., Gulyas, G., Athey, P., Scott, M. J., Wickline, S. A., & Lanza, G. M. (2007). Imaging of Vx-2 rabbit tumors with αvβ3- integrin-targeted 111In nanoparticles. International Journal of Cancer, 120(9), 1951-1957. https://doi.org/10.1002/ijc.22581