Iron oxide-enhanced MR imaging of the liver and spleen: review of the first 5 years
Abstract
Superparamagnetic iron oxide (SPIO) particles are a potent new class of MR contrast agents affording improved detection of hepatic and splenic neoplasms. In this report we review the development of this agent through preclinical studies and early clinical results at Massachusetts General Hospital during a 5-year investigation. SPIO particles are sequestered by normal phagocytic Kupffer cells of the reticuloendothelial system (RES) but are not retained in tumor tissue. Consequently, there is a fivefold increase in T2 relaxation between normal RES tissue and tumor, with a comparable advantage in quantitative signal-to-noise ratio, contrast-to-noise ratio, and lesion detectability in the liver and spleen on MR imaging. Increased lesion conspicuity can be exploited to decrease threshold size for lesion detection to less than 3 mm. Clinically beneficial effects occur with a variety of mildly T2-weighted spin-echo pulse sequences; gradient-echo techniques show even greater benefit after administration of SPIO. Metabolically, pharmaceutical-grade preparations are biodegradable and bioavailable, being rapidly turned over into body iron stores and incorporated into erythrocyte hemoglobin. Early dose-escalation clinical trials have identified a probable clinical dose range of 10-20 mumols Fe/kg body weight. In the United States, SPIO compounds evaluated to date are still approved for use in investigational studies only. Newer commercial formulations currently being evaluated may extend clinical safety margins.
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Due to high liver uptake, iron oxide nanoparticles have been employed relatively extensively for visualizing primary lesions in the liver, such as hepatocellular carcinoma and liver metastases.
“Due to their high liver uptake, iron oxide nanoparticles have been employed relatively extensively for visualizing primary lesions in the liver, e.g. in case of hepatocellular carcinoma (HCC) (Figure 3 A, B) as well as liver metastases (Figure 3 C, D) [144, 145].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [145]
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BackgroundSharkey, J. W., Lewis, P. J. S., Barrow, M., Alwahsh, S. M., Noble, J., Livingstone, E. J., Lennen, R. J., Jansen, M. A., Carrión, J. G., Liptrott, N. J., et al. (2017) · Cytotherapy · doi:10.1016/j.jcyt.2017.01.003 · Cited by 57 · see citing works
“, SPIONs released from necrotic cells) are naturally cleared by the reticuloendothelial system, including Kupffer cells [28], thereby providing the possibility of false-positive MRI hypointense signals from host cells.”
BackgroundOptimization and Validation of FePro Cell Labeling Method
Janic, B., Rad, A. M., Jordan, E. K., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005873 · Cited by 56 · see citing works
“Superparamagnetic iron oxide nanoparticles (SPION), such as ferumoxides, are a class of MRI contrast agents used for imaging pathology in the liver [1], and have also been used as an ex vivo cell labeling agent for various types of mammalian cells for in vivo cellular MRI.”
BackgroundAdvances in Polymeric and Inorganic Vectors for Nonviral Nucleic Acid Delivery
Sunshine, J. C., Bishop, C. J., & Green, J. J. (2011) · Therapeutic Delivery · doi:10.4155/tde.11.14 · Cited by 55 · see citing works
Wang, K., Li, L., Xu, X., Lu, L., Wang, J., Wang, S., Wang, Y., Jin, Z., Zhang, J. Z., & Jiang, Y. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.8b18648 · Cited by 54 · see citing works
Gao, X., Luo, & Wang (2012) · International Journal of Nanomedicine · doi:10.2147/ijn.s32804 · Cited by 53 · see citing works
“35 Moreover, after cellular internalization, hydrolytic enzymes degraded intracellular SPION, and the nanoparticles consequently lost their capacity for contrast enhancement.”
Imaging of HCC—Current State of the Art
Schraml, C., Kaufmann, S., Rempp, H., et al. (2015) · Diagnostics · doi:10.3390/diagnostics5040513 · Cited by 52 · see citing works
“Malignant lesions tend to contain less Kupffer cells and therefore appear less hypointense than healthy liver tissue in SPIO imaging [43,44].”
BackgroundButoescu, N., Seemayer, C. A., Palmer, G., et al. (2009) · Arthritis Research & Therapy · doi:10.1186/ar2701 · Cited by 50 · see citing works
“The magnetic properties of this system come from the encapsulated SPIONs, which are nearly identical to the iron oxide used as a contrast agent in humans [11-13].”
BackgroundKim, Y. K., Kim, C. S., Lee, Y. H., et al. (2004) · American Journal of Roentgenology · doi:10.2214/ajr.182.5.1821217 · Cited by 49 · see citing works
Mn‐DPDP enhancement patterns of hepatocellular lesions on MR images
Vogl, T. J., Hamm, B., Schnell, B., et al. (1993) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.1880030110 · Cited by 48 · see citing works
Contrast agents for MR imaging of the liver
Low, R. N. (1997) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.1880070109 · Cited by 48 · see citing works
Nakamura, H., Ito, N., Kotake, F., et al. (2000) · Journal of Gastroenterology · doi:10.1007/s005350070022 · Cited by 47 · see citing works
“(1) Tumor detection rate by each examination method (dynamic CT, plain MRI, Gd dynamic MRI, and SPIO-MRI) (2) Diagnostic accuracy (3) Comparison among rates of detection of tumors with varying nodular diameters (4) Intratumor blood flow patterns and detection rates (5) Detection rate for each SPIO-MRI sequence (6) His…”
Method
- Authors
- Ferrucci, J. T., & Stark, D. D.
- Affiliations
- Massachusetts General Hospital (US)
- ORCID
- Stark, D D
- Venue
- American Journal of Roentgenology
- Publisher
- American Roentgen Ray Society
- Published
- 1990-11
- Volume
- 155
- Issue
- 5
- Pages
- 943-950
- ISSN
- 0002-9580 (ISSN-L)
- 0361-803X
- 1546-3141
- OpenAlex
- W2068366961
- Cited by
- 279
- References
- 0
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 6 · 2015: 18 · 2014: 9 · 2013: 10 · 2012: 18
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Roentgenology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › MRI in cancer diagnosis
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Keywords
- superparamagnetic iron oxide nanoparticles, MRI contrast agents, liver tumors, splenic neoplasms, Kupffer cells, T2 relaxation, tumor detection, reticuloendothelial system, dose escalation, contrast-to-noise ratio, gradient-echo imaging, iron metabolism
- MeSH terms
- Animals, Humans, Image Enhancement, Iron, Liver Diseases, Magnetic Resonance Imaging, Oxides, Splenic Neoplasms, Ferrosoferric Oxide
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