Nikhil Rammohan1,2, Keith W MacRenaris1, Laura K Moore2, Giacomo Parigi3, Daniel J Mastarone1, Lisa M Manus1, Laura M Lilley1, Adam T Preslar1, Emily A Waters1, Abigail Filicko1, Claudio Luchinat3, Dean Ho4, Thomas J Meade1,2. 1. Department of Chemistry, Molecular Biosciences, Neurobiology, Radiology, and Center for Advanced Molecular Imaging, Northwestern University , Evanston, Illinois 60208, United States. 2. Feinberg School of Medicine, Northwestern University , Chicago, Illinois 60611, United States. 3. Center for Magnetic Resonance (CERM/CIRMMP) and Department of Chemistry, University of Florence , Sesto Fiorentino, Florence 50019, Italy. 4. School of Dentistry, University of California , Los Angeles, California 90095, United States.
Abstract
The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth, and metastatic potential within the intact organism. Magnetic resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and the absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies. We have developed carbon-based nanodiamond-gadolinium(III) aggregates (NDG) for MR imaging that demonstrated remarkable properties for cell tracking in vivo. First, NDG had high relaxivity independent of field strength, a finding unprecedented for gadolinium(III) [Gd(III)]-nanoparticle conjugates. Second, NDG demonstrated a 300-fold increase in the cellular delivery of Gd(III) compared to that of clinical Gd(III) chelates without sacrificing biocompatibility. Further, we were able to monitor the tumor growth of NDG-labeled flank tumors by T1- and T2-weighted MR imaging for 26 days in vivo, longer than was reported for other MR CAs or nuclear agents. Finally, by utilizing quantitative maps of relaxation times, we were able to describe tumor morphology and heterogeneity (corroborated by histological analysis), which would not be possible with competing molecular imaging modalities.
The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth, and metastatic potential within the intact organism. Magnetic resonance (MR) imaging is invaluable for tracking n class="Disease">cancer cells in vivo as it benefits from high spatial resolution and the absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies. We have developed carbon-based nanodiamond-gadolinium(III) aggregates (NDG) for MR imaging that demonstrated remarkable properties for cell tracking in vivo. First, NDG had high relaxivity independent of field strength, a finding unprecedented for gadolinium(III) [Gd(III)]-nanoparticle conjugates. Second, NDG demonstrated a 300-fold increase in the cellular delivery of Gd(III) compared to that of clinical Gd(III) chelates without sacrificing biocompatibility. Further, we were able to monitor the tumor growth of NDG-labeled flank tumors by T1- and T2-weighted MR imaging for 26 days in vivo, longer than was reported for other MR CAs or nuclear agents. Finally, by utilizing quantitative maps of relaxation times, we were able to describe tumor morphology and heterogeneity (corroborated by histological analysis), which would not be possible with competing molecular imaging modalities.
Entities:
Keywords:
MRI; Nanodiamonds; cancer; gadolinium; in vivo
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