Abstract
PurposeTo develop and characterize a new paramagnetic contrast agent for molecular imaging by MRI.MethodsA contrast agent was developed for direct MRI detection through the paramagnetically shifted proton magnetic resonances of two chemically equivalent tert‐butyl reporter groups within a dysprosium(III) complex. The complex was characterized in phantoms and imaged in physiologically intact mice at 7 Tesla (T) using three‐dimensional (3D) gradient echo and spectroscopic imaging (MRSI) sequences to measure spatial distribution and signal frequency.ResultsThe reporter protons reside ∼6.5 Å from the paramagnetic center, resulting in fast T 1 relaxation (T 1 = 8 ms) and a large paramagnetic frequency shift exceeding 60 ppm. Fast relaxation allowed short scan repetition times with high excitation flip angle, resulting in high sensitivity. The large dipolar shift allowed direct frequency selective excitation and acquisition of the dysprosium(III) complex, independent of the tissue water signal. The biokinetics of the complex were followed in vivo with a temporal resolution of 62 s following a single, low‐dose intravenous injection. The lower concentration limit for detection was ∼23 μM. Through MRSI, the temperature dependence of the paramagnetic shift (0.28 ppm.K−1) was exploited to examine tissue temperature variation.ConclusionsThese data demonstrate a new MRI agent with the potential for physiological monitoring by MRI. Magn Reson Med 77:1307–1317, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Highlights
Contrast agents are routinely used to improve the diagnostic specificity of MRI
We have previously developed a small molecular weight 19Flabelled lanthanide metal chelate, in which the structure was manipulated such that the dipolar field of the metal enhanced the longitudinal relaxation rate of the 19F nuclei
These peaks arise from two isomers that are in slow chemical exchange
Summary
Contrast agents are routinely used to improve the diagnostic specificity of MRI. The most common agents use chelated gadolinium in which the local dipolar field of the Gd ion causes an increase in the longitudinal relaxation rate (R1) of water molecules within the local vicinity (and can increase tissue RÃ2 through local susceptibility effects). The presence of the contrast agent is inferred from the resulting intensity change on T1 or T2Ã weighted MRI, respectively. These contrast systems are entirely passive, accumulating and being removed from tissues by diffusive processes only. Agents that bind to a range of targets, such as collagen in fibrotic scar tissue [2,3,4] or the endothelial wall [5,6] have been developed All of these agents rely on indirect detection via changes in water relaxation rates (R1, R2, or RÃ2) through conventional gadolinium chelates [1] or iron oxide systems [7], rather than detecting the contrast molecule directly
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