Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray Fluorescence

The inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating proces...

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Main Authors: Paul J. Endres, Keith W. MacRenaris, Stefan Vogt, Matthew J. Allen, Thomas J. Meade
Format: Article
Language:English
Published: SAGE Publishing 2006-10-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2006.00026
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author Paul J. Endres
Keith W. MacRenaris
Stefan Vogt
Matthew J. Allen
Thomas J. Meade
author_facet Paul J. Endres
Keith W. MacRenaris
Stefan Vogt
Matthew J. Allen
Thomas J. Meade
author_sort Paul J. Endres
collection DOAJ
description The inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating processes and cycles in developmental biology. Conversely, a contrast agent with the ability to permeate cell membranes could be used in visualizing cell patterning, cell fate mapping, gene therapy, and, eventually, noninvasive cancer diagnosis. Therefore, we describe the synthesis and quantitative imaging of four contrast agents with the capability to cross cell membranes in sufficient quantity for detection. Each agent is based on the conjugation of a Gd(III) chelator with a cellular transduction moiety. Specifically, we coupled Gd(III)–diethylenetriaminepentaacetic acid DTPA and Gd(III)–1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with an 8–amino acid polyarginine oligomer and an amphipathic stilbene molecule, 4-amino-4'-( N,N -dimethylamino)stilbene. The imaging modality that provided the best sensitivity and spatial resolution for direct detection of the contrast agents is synchrotron radiation x-ray fluorescence (SR-XRF). Unlike optical microscopy, SR-XRF provides two-dimensional images with resolution 10 3 better than 153 Gd gamma counting, without altering the agent by organic fluorophore conjugation. The transduction efficiency of the intracellular agents was evaluated by T 1 analysis and inductively coupled plasma mass spectrometry to determine the efficacy of each chelate-transporter combination.
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spelling doaj-art-66a7c9e52dc3444ea7536e55936928a52025-01-03T00:12:13ZengSAGE PublishingMolecular Imaging1536-01212006-10-01510.2310/7290.2006.0002610.2310_7290.2006.00026Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray FluorescencePaul J. EndresKeith W. MacRenarisStefan VogtMatthew J. AllenThomas J. MeadeThe inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating processes and cycles in developmental biology. Conversely, a contrast agent with the ability to permeate cell membranes could be used in visualizing cell patterning, cell fate mapping, gene therapy, and, eventually, noninvasive cancer diagnosis. Therefore, we describe the synthesis and quantitative imaging of four contrast agents with the capability to cross cell membranes in sufficient quantity for detection. Each agent is based on the conjugation of a Gd(III) chelator with a cellular transduction moiety. Specifically, we coupled Gd(III)–diethylenetriaminepentaacetic acid DTPA and Gd(III)–1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with an 8–amino acid polyarginine oligomer and an amphipathic stilbene molecule, 4-amino-4'-( N,N -dimethylamino)stilbene. The imaging modality that provided the best sensitivity and spatial resolution for direct detection of the contrast agents is synchrotron radiation x-ray fluorescence (SR-XRF). Unlike optical microscopy, SR-XRF provides two-dimensional images with resolution 10 3 better than 153 Gd gamma counting, without altering the agent by organic fluorophore conjugation. The transduction efficiency of the intracellular agents was evaluated by T 1 analysis and inductively coupled plasma mass spectrometry to determine the efficacy of each chelate-transporter combination.https://doi.org/10.2310/7290.2006.00026
spellingShingle Paul J. Endres
Keith W. MacRenaris
Stefan Vogt
Matthew J. Allen
Thomas J. Meade
Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray Fluorescence
Molecular Imaging
title Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray Fluorescence
title_full Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray Fluorescence
title_fullStr Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray Fluorescence
title_full_unstemmed Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray Fluorescence
title_short Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray Fluorescence
title_sort quantitative imaging of cell permeable magnetic resonance contrast agents using x ray fluorescence
url https://doi.org/10.2310/7290.2006.00026
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