Iron oxide MR contrast agents for molecular and cellular imaging
Abstract
Molecular and cellular MR imaging is a rapidly growing field that aims to visualize targeted macromolecules or cells in living organisms. In order to provide a different signal intensity of the target, gadolinium-based MR contrast agents can be employed although they suffer from an inherent high threshold of detectability. Superparamagnetic iron oxide (SPIO) particles can be detected at micromolar concentrations of iron, and offer sufficient sensitivity for T2(*)-weighted imaging. Over the past two decades, biocompatible particles have been linked to specific ligands for molecular imaging. However, due to their relatively large size and clearance by the reticuloendothelial system (RES), widespread biomedical molecular applications have yet to be implemented and few studies have been reproduced between different laboratories. SPIO-based cellular imaging, on the other hand, has now become an established technique to label and detect the cells of interest. Imaging of macrophage activity was the initial and still is the most significant application, in particular for tumor staging of the liver and lymph nodes, with several products either approved or in clinical trials. The ability to now also label non-phagocytic cells in culture using derivatized particles, followed by transplantation or transfusion in living organisms, has led to an active research interest to monitor the cellular biodistribution in vivo including cell migration and trafficking. While most of these studies to date have been mere of the 'proof-of-principle' type, further exploitation of this technique will be aimed at obtaining a deeper insight into the dynamics of in vivo cell biology, including lymphocyte trafficking, and at monitoring therapies that are based on the use of stem cells and progenitors.
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Different parameters like core size of SPION, shape, hydrodynamic diameter, size distribution, nanoparticle coating and aggregation influence the longitudinal and transverse relaxivities of iron oxide nanoparticles.
“Different parameters like core size of SPION, shape, hydrodynamic diameter, size distribution, nanoparticles coating and aggregation influence the longitudinal and transverse relaxivities of iron oxide nanoparticles.”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [111]
r2 typically shows a linear increase with increasing particle core size from 4-5 to 18 nm, while r1 remains rather invariant for particles larger than approximately 8 nm.
“While r2 typically shows a linear increase with increasing the particle core size from 4-5 to 18 nm, r1 remains rather invariant for particles larger than approximately 8 nm.”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [111]
For small clusters, r2 gradually increases with hydrodynamic diameter up until approximately 80 nm.
“Regarding the effect of hydrodynamic diameter and aggregation on relaxivities, r2 gradually increases with the hydrodynamic diameter (up until approximately 80 nm) for small clusters, because SPION are consistently dispersed in water and protons diffuse between the magnetic cores.”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [111]
For large clusters, if the size exceeds 90 nm, r2 decreases with increasing size due to a reduction in proton exchange rate arising from reduced surface accessibility.
“In the case of large clusters, if the size exceeds 90 nm, r2 decreases with increasing size due to a reduction in the proton exchange rate arising from the reduction in surface accessibility.”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [111]
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- Authors
- Bulte, J. W. M., & Kraitchman, D. L.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Bulte, Jeff W. M.
- Venue
- NMR in Biomedicine
- Publisher
- Wiley
- Published
- 2004-11
- Volume
- 17
- Issue
- 7
- Pages
- 484-499
- ISSN
- 0952-3480 (ISSN-L)
- 1099-1492
- OpenAlex
- W1976062460
- Cited by
- 1,500
- References
- 125
- Citations by year
- 2026: 21 · 2025: 17 · 2024: 25 · 2023: 27 · 2022: 46 · 2021: 49 · 2020: 41 · 2019: 42 · 2018: 69 · 2017: 58 · 2016: 81 · 2015: 112 · 2014: 96 · 2013: 109 · 2012: 119
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NMR in Biomedicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society
- National Institutes of Health (5r01hl063439-04, 5r01ns045062-10)
- National Heart, Lung, and Blood Institute (R01HL63439, K02HL004193, KO2 HL04193, R01HL073223)
- National Institute of Neurological Disorders and Stroke (R01-NS045062)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Physical Sciences › Materials Science › Materials Chemistry › Lanthanide and Transition Metal Complexes
- Keywords
- superparamagnetic iron oxide nanoparticles, MRI contrast agents, molecular imaging, cell imaging, cell labeling, cell tracking, T2-weighted imaging, reticuloendothelial system clearance, macrophage imaging, tumor staging, cell biodistribution, lymphocyte migration, gadolinium alternatives
- MeSH terms
- Animals, Biopolymers, Cell Movement, Cell Physiological Phenomena, Cell Separation, Contrast Media, Ferric Compounds, Humans, Image Enhancement, Magnetic Resonance Imaging, Molecular Biology, Particle Size, Gene Expression Profiling
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