In vivo characterization of tumor vasculature using iodine and gold nanoparticles and dual energy micro-CT.

Published

Journal Article

Tumor blood volume and vascular permeability are well established indicators of tumor angiogenesis and important predictors in cancer diagnosis, planning and treatment. In this work, we establish a novel preclinical imaging protocol which allows quantitative measurement of both metrics simultaneously. First, gold nanoparticles are injected and allowed to extravasate into the tumor, and then liposomal iodine nanoparticles are injected. Combining a previously optimized dual energy micro-CT scan using high-flux polychromatic x-ray sources (energies: 40 kVp, 80 kVp) with a novel post-reconstruction spectral filtration scheme, we are able to decompose the results into 3D iodine and gold maps, allowing simultaneous measurement of extravasated gold and intravascular iodine concentrations. Using a digital resolution phantom, the mean limits of detectability (mean CNR = 5) for each element are determined to be 2.3 mg mL(-1) (18 mM) for iodine and 1.0 mg mL(-1) (5.1 mM) for gold, well within the observed in vivo concentrations of each element (I: 0-24 mg mL(-1), Au: 0-9 mg mL(-1)) and a factor of 10 improvement over the limits without post-reconstruction spectral filtration. Using a calibration phantom, these limits are validated and an optimal sensitivity matrix for performing decomposition using our micro-CT system is derived. Finally, using a primary mouse model of soft-tissue sarcoma, we demonstrate the in vivo application of the protocol to measure fractional blood volume and vascular permeability over the course of five days of active tumor growth.

Full Text

Duke Authors

Cited Authors

  • Clark, DP; Ghaghada, K; Moding, EJ; Kirsch, DG; Badea, CT

Published Date

  • March 2013

Published In

Volume / Issue

  • 58 / 6

Start / End Page

  • 1683 - 1704

PubMed ID

  • 23422321

Pubmed Central ID

  • 23422321

Electronic International Standard Serial Number (EISSN)

  • 1361-6560

International Standard Serial Number (ISSN)

  • 0031-9155

Digital Object Identifier (DOI)

  • 10.1088/0031-9155/58/6/1683

Language

  • eng