Primed infusion with delayed equilibrium of Gd.DTPA for enhanced imaging of small pulmonary metastases

PLoS One. 2013;8(1):e54903. doi: 10.1371/journal.pone.0054903. Epub 2013 Jan 31.

Abstract

Objectives: To use primed infusions of the magnetic resonance imaging (MRI) contrast agent Gd.DTPA (Magnevist), to achieve an equilibrium between blood and tissue (eqMRI). This may increase tumor Gd concentrations as a novel cancer imaging methodology for the enhancement of small tumor nodules within the low signal-to-noise background of the lung.

Methods: A primed infusion with a delay before equilibrium (eqMRI) of the Gd(III) chelator Gd.DTPA, via the intraperitoneal route, was used to evaluate gadolinium tumor enhancement as a function of a bolus injection, which is applied routinely in the clinic, compared to gadolinium maintained at equilibrium. A double gated (respiration and cardiac) spin-echo sequence at 9.4T was used to evaluate whole lungs pre contrast and then at 15 (representative of bolus enhancement), 25 and 35 minutes (representative of eqMRI). This was carried out in two lung metastasis models representative of high and low tumor cell seeding. Lungs containing discrete tumor nodes where inflation fixed and taken for haematoxylin and eosin staining as well as CD34 staining for correlation to MRI.

Results: We demonstrate that sustained Gd enhancement, afforded by Gd equilibrium, increases the detection of pulmonary metastases compared to bolus enhancement and those tumors which enhance at equilibrium are sub-millimetre in size (<0.7 mm(2)) with a similar morphology to early bronchoalveolar cell carcinomas.

Conclusion: As Gd-chelates are routinely used in the clinic for detecting tumors by MRI, this methodology is readily transferable to the clinic and advances MRI as a methodology for the detection of small pulmonary tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chelating Agents / administration & dosage
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacokinetics
  • Contrast Media / administration & dosage
  • Contrast Media / chemistry
  • Contrast Media / pharmacokinetics
  • Gadolinium / chemistry
  • Gadolinium DTPA / administration & dosage
  • Gadolinium DTPA / chemistry
  • Gadolinium DTPA / pharmacokinetics*
  • HEK293 Cells
  • Humans
  • Infusions, Parenteral / methods*
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Neoplasm Metastasis
  • Time Factors
  • Tumor Burden*

Substances

  • Chelating Agents
  • Contrast Media
  • Gadolinium
  • Gadolinium DTPA