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Global Translational Medicine SPION for cancer theranostics

of a contrast agent is measured by its r (for T ) or r (for company voluntarily withdrew Combidex from the United
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T ) relaxivity. There are two main types of contrast agents: States market.
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positive contrast agents, which mainly shorten T for bright Ferumoxytol, another candidate, comprises polyglucose
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images, and negative contrast agents, which primarily sorbitol carboxymethyl ether-coated SPIONs with a
shorten T , leading to darker images that are effective for hydrodynamic size of 20 – 40 nm. It was developed to
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distinguishing between healthy and diseased tissues.
address iron deficiency anemia in patients with chronic
4.1.1. SPIONs as spin-spin MRI contrast agents kidney disease. 37,41 However, ferumoxytol was associated
with side effects, leading the FDA to issue a black box
Recent studies have shown that SPIONs with particle sizes warning due to the risk of serious allergic reactions. Despite
smaller than 20 nm are widely used as negative contrast these limitations, ferumoxytol remains one of the few
agents. The MRI signal contrast of SPIONs is higher than SPION formulations still in use today, both for its intended
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that of paramagnetic contrast agents, such as gadolinium purpose and off-label as an MRI angiography agent in
Gd(III) and manganese Mn(II) based complexes, due to the patients who cannot receive Gd-based contrast agents.
higher transverse relaxivity of SPIONs (r value) compared
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to their longitudinal relaxivity (r value). In addition, Ferucarbotran (Sienna+/Magtrace), consisting of
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SPIONs exhibit chemical stability, biocompatibility, and carboxydextran-coated SPIONs with a hydrodynamic
biodegradability under in vivo conditions, as they integrate size of 59 nm, was developed by Endomagnetics Ltd. for
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into the bloodstream as normal iron ions. Building on sentinel lymph node identification. To the best of our
their exceptional magnetic properties and the significant knowledge, these products have not been used for imaging
influence of SPIONs on T relaxation times, numerous applications yet.
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candidates have been developed for use as negative Other notable mentions include formulations used as
contrast agents in MRI. Several iron oxide-based imaging oral gastrointestinal contrast agents, such as ferumoxsil
probes, including ferumoxides (Feridex/Endorem), (marketed as GastroMARK in Europe and Lumirem in the
ferucarbotran (Resovist/Supravist), ferumoxtran-10 United States) and ferristene (Abdoscan ). These SPION-
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(Sinerem/Combidex), ferumoxsil (Lumirem/Gastromark), based formulations, coated with insoluble materials – silica
and ferristene (Abdoscan), have been developed and for ferumoxsil (~300 nm core size) and polystyrene for
evaluated in clinical trials. ferristene (~3,500 nm core size) – are considered safe and
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Ferumoxides, developed by Guerbet, were the first effective. Ferumoxsil remains the only SPION approved
commercially available dextran-coated SPIONs with a by the FDA for imaging applications, specifically for
hydrodynamic size of 40 – 150 nm. 37,38 They were approved gastrointestinal and bowel contrast.
by the United States Food and Drug Administration Although some formulations have been associated
(FDA) in 1996 for use in Europe, specifically for imaging with side effects, ongoing advancements continue to focus
liver tumors. However, Ferridex was withdrawn from the on developing more effective SPION-based formulations
market in 2011 due to its severe side effects and lack of for improved cancer imaging and diagnosis applications.
demand. Although some formulations have been associated with
Resovist, developed by Bayer Healthcare, consists of side effects, ongoing advancements aim to develop more
carboxydextran-coated SPIONs with a hydrodynamic size effective SPION-based formulations for enhanced cancer
of 60 – 80 nm and was used for liver imaging. It is considered imaging and diagnostic applications.
a standard contrast agent in the development of magnetic Numerous efforts have been made to enhance the
particle imaging. 37,39 Supravist, another carboxydextran- sensitivity of cancer cell diagnosis. One strategy involves
coated SPION formulation with a hydrodynamic size of 20 increasing the relaxivity of SPIONs to achieve more
– 25 nm, was developed for longer circulation times, with sensitive MRI applications. Ding et al. synthesized
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T and T properties. However, it has not been marketed laponite-stabilized SPIONs using a coprecipitation
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for clinical use, and the formulation was discontinued in synthesis route and observed that the T₂ relaxivity of the
2008 due to reports of severe allergic reactions. synthesized NPs (475.9/mM/s) was almost twice as high
Developed by AMAG Pharmaceuticals, ferumoxtran as that of bare Fe O NPs (247.6/mM/s). They observed
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comprises dextran-coated SPIONs with a hydrodynamic that laponite-stabilized SPIONs successfully lowered the
size of 20 – 50 nm. 37,40 Initially used for prostate cancer MRI signal intensity of tumors following intravenous
lymph node metastasis imaging, the FDA issued a safety injection, in addition to acting as a contrast agent for
alert in 2008, warning of the potential risk of serious MRI of cancer cells in vitro. In another study, Zhao et al.
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allergic reactions. Consequently, the manufacturing fabricated concave octopod-shaped Fe O NPs using a
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Volume 4 Issue 2 (2025) 40 doi: 10.36922/gtm.8464