Primed Infusion with Delayed Equilibrium of Gd.DTPA for Enhanced Imaging of Small Pulmonary Metastases

Tammy L Kalber,Simon Walker-Samuel,Bernard M Siow,Katherine L Ordidge,Adrienne E Campbell-Washburn,Sam M Janes,Mark F Lythgoe,Elizabeth Sage,Anthony N Price,Vladimir V Kalinichenko

doi:10.1371/journal.pone.0054903

Tammy L Kalber, Simon Walker-Samuel + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0054903

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Journal: PLoS ONE	Publication Date: Jan 31, 2013
Citations: 43	License type: CC BY 4.0

Affiliation: University College London

Abstract

ObjectivesTo 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.MethodsA 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.ResultsWe 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 mm2) with a similar morphology to early bronchoalveolar cell carcinomas.ConclusionAs 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.

Highlights

Lung cancer is the commonest cause of cancer death worldwide with 152,000 deaths each year in the US (NCI 2011)
In this study, primed infusions with a delay before equilibrium of the Gd(III) chelator Gd.DTPA (Magnevist) were 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
Two models of lung metastasis representative of high and low tumor cell seeding were evaluated by eqMRI (Figure 1, experimental dosing plan)

Summary

Introduction

Lung cancer is the commonest cause of cancer death worldwide with 152,000 deaths each year in the US (NCI 2011). Accurate and cost effective screening methods for lung cancer are desperately needed. Screening should be sensitive to small nodules, specific to the disease, able to detect suitability of patients for radical treatments and be non-invasive. Prior screening trials with chest radiographs have not found a reduction in lung cancer mortality [1,2,3]. Computer tomography (CT) is more sensitive than chest radiography and has recently been shown to be effective at reducing lung cancer mortality, the feasibility and cost effectiveness of mass CT screening is still disputed [4,5,6]. It lacks the specificity to distinguish between benign and cancerous tumors, and nodules of 4 to 10 mm are followed up by repeated CT scans thereby increasing radiation burden [8]

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