Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast

Ananta, Jeyarama S.; Godin, Biana; Sethi, Richa; Moriggi, Loïck; Liu, Xuewu; Serda, Rita E.; Krishnamurthy, Ramkumar; Muthupillai, Raja; Bolskar, Robert D.; Helm, Lothar; Ferrari, Mauro; Wilson, Lon J.; Decuzzi, Paolo

doi:10.1038/nnano.2010.203

Cited by 375 publications

(396 citation statements)

References 32 publications

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“…Remarkably, ProCA32 retains r 1 of 21.9 mM −1 ·s −1 at room temperature and 4.7 T, and r 2 is 56.9 mM −1 ·s −1 ; r 1 is 18 mM −1 ·s −1 at 7 T (Table S2), which is not predicted by the usual relaxation equations (17,18). In addition, 5 μM ProCA32 is able to generate a level of contrast similar to 50 μM Eovist with T 1 -weighted spin echo and at 4.7 T (Fig.…”

Section: Resultsmentioning

confidence: 92%

Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

Xue

Yang²,

Qiao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

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With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd 3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd 3+ and a 10 11 -fold greater selectivity for Gd 3+ over Zn 2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r 1 /r 2 : 66.8 mmol −1 ·s −1 / 89.2 mmol −1 ·s −1 per particle). Using T 1 -and T 2 -weighted, as well as T 2 /T 1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10-20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.MRI | uveal melanoma | metastasis | contrast agents | T 2 /T 1 ratio imaging T umor metastasis is the main cause of nearly all human cancerrelated deaths. Liver is a common site for metastases of a variety of cancers, including melanoma, breast, pancreatic, and colon cancers (1, 2). For example, uveal melanoma, the most common primary intraocular tumor, has a 40% risk of metastasizing to the liver within 10 y of diagnosis of the primary tumor. Hepatic metastases, which occur in 95% of patients with uveal melanoma metastasis, result in death in almost all cases. This high death rate is related to the recognition of liver metastasis at a late clinical stage (at stage II or later in the TNM system) in which the metastatic uveal melanoma is resistant to currently available systemic chemotherapies (3, 4). The liver may also give rise to primary tumors such as hepatocellular carcinoma (HCC), which is the most common primary malignancy worldwide (5). However, currently there is no reliable way to detect primary liver cancer and hepatic metastases at early stages with high sensitivity and specificity.MRI is a widely used clinical imaging modality that provides exquisite soft-tissue contrast without using ionizing radiation (6, 7). More than 35% of MRI scans use MRI contrast agents, particularly paramagnetic gadolinium (Gd 3+ )-based contrast agents, which shorten T 1 and lead to an increase in MRI intensity (8). All clinically approved Gd 3+ -containing contrast agents are based on small chelators with relaxivity (r 1 and r 2 ) values around 4-6 mM −1 ·s −1 . Their low relaxivities severely limit the sensitivity of current MR imaging methods with respect to detection of lesions and treatment planning and monitoring. Repeat MRI scans are frequently requested for patients with ambiguous small lesions and are used as a routine follow-up modality for highrisk patients, but t...

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Section: Resultsmentioning

confidence: 92%

Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

Xue

Yang²,

Qiao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

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“…In particular, these commercially available T 2 contrast agents were synthesized in aqueous media and, consequently, exhibit poor crystallinity and relatively low relaxivity 12 . Thus, the primary limitation of MRI is the relatively low sensitivity of the contrast agents 13,14 . The development of new T 2 contrast agents with high relaxivity for high-performance MRI diagnosis is required.…”

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confidence: 99%

Octapod iron oxide nanoparticles as high-performance T2 contrast agents for magnetic resonance imaging

et al. 2013

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Spherical superparamagnetic iron oxide nanoparticles have been developed as T 2 -negative contrast agents for magnetic resonance imaging in clinical use because of their biocompatibility and ease of synthesis; however, they exhibit relatively low transverse relaxivity. Here we report a new strategy to achieve high transverse relaxivity by controlling the morphology of iron oxide nanoparticles. We successfully fabricate size-controllable octapod iron oxide nanoparticles by introducing chloride anions. The octapod iron oxide nanoparticles (edge length of 30 nm) exhibit an ultrahigh transverse relaxivity value (679.3±30 mM À 1 s À 1 ), indicating that these octapod iron oxide nanoparticles are much more effective T 2 contrast agents for in vivo imaging and small tumour detection in comparison with conventional iron oxide nanoparticles, which holds great promise for highly sensitive, early stage and accurate detection of cancer in the clinic.

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“…Here, the coordination and chemical exchange of the surrounding protons are restricted by the so‐called geometrical confinement effect due to the unique architecture,12 which results in enhanced T 1 contrast. Restricted water diffusion due to the concentration effect could disturb the motional averaging effect of T 2 relaxation and offer improved T 2 contrast 16.…”

mentioning

confidence: 99%

Novel Intrapolymerization Doped Manganese‐Eumelanin Coordination Nanocomposites with Ultrahigh Relaxivity and Their Application in Tumor Theranostics

et al. 2018

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While magnetic resonance imaging contrast agents have potential in noninvasive image‐guided tumor treatment, further developments are needed to increase contrast, biodegradability, and safety. Here, novel engineered manganese‐eumelanin coordination nanocomposites (MnEMNPs) are developed via a facile one‐pot intrapolymerization doping (IPD) approach in aqueous solution, through simple chemical oxidation–polymerization of the 3,4‐dihydroxy‐DL‐phenylalanine precursor with potassium permanganate serving as the Mn source and an oxidant. The resulting MnEMNPs possess ultrahigh longitudinal relaxivity (r 1 value up to 60.8 mM−1 s−1 at 1.5 T) attributed to the high manganese doping efficiency (>10%) and geometrically confined conformation. Due to their high manganese chelation stability, excellent biocompatibility, and strong near‐infrared absorption, high‐performance longitudinal‐transverse (T 1 ‐T 2) dual‐modal magnetic resonance/photoacoustic imaging and photothermal tumor ablation are achieved. Furthermore, the hydrogen peroxide‐triggered decomposition behavior of MnEMNPs circumvents the poor biodegradation issue of many nanomaterials. This facile, convenient, economical, and efficient IPD strategy will open up new avenues for the development of high‐performance multifunctional theranostic nanoplatforms in bionanomedicine.

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Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast

Cited by 375 publications

References 32 publications

Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

Octapod iron oxide nanoparticles as high-performance T2 contrast agents for magnetic resonance imaging

Novel Intrapolymerization Doped Manganese‐Eumelanin Coordination Nanocomposites with Ultrahigh Relaxivity and Their Application in Tumor Theranostics

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