Improved paramagnetic chelate for molecular imaging with MRI

Winter, Patrick M.; Athey, Phillip S.; Kiefer, Garry E.; Gulyás, Gabriella; Frank, Keith; Fuhrhop, Ralph W.; Robertson, David W.; Wickline, Samuel A.; Lanza, Gregory M.

doi:10.1016/j.jmmm.2005.01.062

Cited by 42 publications

(56 citation statements)

References 15 publications

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“…[13][14][15] The surfactant comixture generally included 97.9 mol % lecithin (Avanti Polar Lipids), 0.1 mol % vitronectin antagonist, 16 conjugated to PEG 2000 -phosphatidylethanolamine 15 (Avanti Polar Lipids), and 1 mol % of a lipophilic chelate, 17 methoxy-DOTA-caproyl-phosphatidylethanolamine (MeO-DOTA-PE, Dow Chemical Company). The surfactant components were prepared as published elsewhere, 13 combined with PFOB and distilled deionized water and emulsified (Model S110, Microfluidics) at 20,000 PSI for 4 min.…”

Section: Methodsmentioning

confidence: 99%

Imaging of Vx‐2 rabbit tumors with α_νβ₃‐integrin‐targeted ¹¹¹In nanoparticles

Lijowski

Zhang

et al. 2007

Intl Journal of Cancer

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118

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Earlier tumor detection can improve 5-year survival of patients, particularly among those presenting with cancers less than 1 cm in diameter. a m b 3 - Targeted 111 In nanoparticles (NP) were developed and studied for detection of tumor angiogenesis. Studies were conducted in New Zealand white rabbits implanted 12 days earlier with Vx-2 tumor. a m b 3 - Targeted 111 In/NP bearing 10 111In/NP vs. 1 111In/NP nuclide payloads were compared to nontargeted radiolabeled control particles. In vivo competitive binding studies were used to assess ligand-targeting specificity. a m b 3 -Integrin-targeted NP with 10 111In/NP provided better (p < 0.05) tumor-to-muscle ratio contrast (6.3 6 0.2) than 1 111In/NP (5.1 6 0.1) or nontargeted particles with 10 111In/NP (3.7 6 0.1) over the initial 2-hr postinjection. At 18 hr, mean tumor activity in rabbits receiving a m b 3 -integrin-targeted NP was 4-fold higher than the nontargeted control. Specificity of the NP for the tumor neovasculature was supported by in vivo competition studies and by fluorescence microscopy of a m b 3 -targeted fluorescent-labeled NP. Biodistribution studies revealed that the primary clearance organ in rabbits as a %ID/g tissue was the spleen. Circulatory half-life (t 1/2b ) was estimated to be 5 hr using a 2-compartment model. a m b 3 - Targeted 111 In perfluorocarbon NP may provide a clinically useful tool for sensitively detecting angiogenesis in nascent tumors, particularly in combination with secondary highresolution imaging modalities, such as MRI. ' 2007 Wiley-Liss, Inc.Key words: indium; angiogenesis; integrin; nanoparticles; Vx2; cancer Data accumulated over the last 25 years in the surveillance, epidemiology and end results cancer registry support the principle that earlier tumor detection improves 5-year survival of patients with either localized or regional invasive breast carcinoma. 1 Improvements in survival were correlated with an overall downward shift in tumor size distribution, with particular advantage noted among patients presenting with cancers less than 1 cm. A widespread desire to detect and treat cancer earlier has spawned interest in molecular imaging and genomic-proteomic technologies, which in combination with new strategies to treat cancer may further improve cancer survival.One approach to identifying small solid tumors has involved early detection of angiogenesis by targeting unique biosignatures of neovascular endothelium, such as a v b 3 -integrin. We have previously demonstrated that paramagnetic perfluorocarbon emulsions targeted to the a v b 3 -integrin can be used to detect the neovasculature of tumors 30 mm 3 at clinical field strengths (1.5 T). Because perfluorocarbon nanoparticles (NP) have a nominal particle size of 250 nm and are constrained within the vasculature, access to a v b 3 -integrin expressed on extravascular macrophages, smooth muscle and other cells is sterically precluded. MRI provides outstanding high-resolution images of even minute tumors enhanced by the bound paramagnetic NP; however, the ...

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Section: Methodsmentioning

confidence: 99%

Imaging of Vx‐2 rabbit tumors with α_νβ₃‐integrin‐targeted ¹¹¹In nanoparticles

Lijowski

Zhang

et al. 2007

Intl Journal of Cancer

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118

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“…The partial volume dilution effect has often led to the failure of targeted contrast in vivo. 25 Extracellular agents are typically Gd chelates of linear or macrocyclic polyaminocarboxylate ligands, and constitute the most important class of MRI contrast agents available. Initial attempts to target MRI focused on coupling Gd atoms directly to antibodies or proteins, but these approaches delivered insufficient paramagnetic material to effectively decrease local relaxation times, and provided inadequate MR signal enhancement in T 1 images at typical clinical field strengths.…”

Section: T 1 Contrast Agentsmentioning

confidence: 99%

“…26 To produce targeting agents, macromolecular constructs, such as liposomes, micelles, fluorinated nanoparticles, dendrimers, and polymers, have been prepared. 17,25,27 The resulting nanoparticles have greater paramagnetic metal surface payloads that rotate or tumble more slowly than small-molecule organometallic compounds typically used as blood-pool agents. 28 …”

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confidence: 99%

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

Estelrich¹,

Sánchez-Martín²,

Busquets³

2015

IJN

276

106

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Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times ( T 1 , spin–lattice relaxation and T 2 , spin–spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T 1 and T 2 increases the corresponding relaxation rates, 1/ T 1 and 1/ T 2 , producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T 2 -weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T 1 -weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents.

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“…For lanthanide ion based contrast agents, this was realized in various ways and different materials have been proposed including: Gd-loaded apoferritin, which allows the visualization of hepatocytes when the number of Gd-complexes per cell is about 4 × 10 7 , 5 perfluorocarbon nanoparticles, which contain around 94 200 Gd 3+ ions per particle providing extremely high relaxivity per particle and which have been already successfully used in molecular imaging of angiogenesis. [6][7][8][9][10] Alternatively, this may be achieved with superparamagnetic (SPM) particles, single domain ferromagnets possessing a very high magnetic moment (around 10 4 µ B ). 11,12 SPM particles have a much smaller effect on the T 1 water proton relaxation time than on the T 2 .…”

Section: Introductionmentioning

confidence: 99%

NMR Transversal Relaxivity of Suspensions of Lanthanide Oxide Nanoparticles

et al. 2007

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Aqueous suspensions of paramagnetic lanthanide oxide nanoparticles have been studied by NMR relaxometry. The observed R 2 * relaxivities are explained by the static dephasing regime (SDR) theory. The corresponding R 2 relaxivities are considerably smaller and are strongly dependent on the interval between the two refocusing pulses. The experimental data are rationalized by assuming the value of the diffusion correlation time, τ D , to be very long in a layer with adsorbed xanthan on the particle's surface. In this layer, the refocusing pulses are fully effective and R 2 ≈ 0. Outside this layer, the diffusion model for weakly magnetized particles was applied. From the fit of the experimental relaxation data with this model, both the particle radii (r p ) and the radii of the spheres, within which the refocusing pulses are fully effective (r diff ), were estimated. The values of r p obtained are in agreement with those determined by dynamic light scattering. Because the value of r diff depends on the external magnetic field B and on the magnetic moment of the lanthanide of interest (µ eff 2 ), the R 2 relaxivity was found to be proportional to B and to µ eff 2 .

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Improved paramagnetic chelate for molecular imaging with MRI

Cited by 42 publications

References 15 publications

Imaging of Vx‐2 rabbit tumors with α_νβ₃‐integrin‐targeted ¹¹¹In nanoparticles

Imaging of Vx‐2 rabbit tumors with α_νβ₃‐integrin‐targeted ¹¹¹In nanoparticles

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

NMR Transversal Relaxivity of Suspensions of Lanthanide Oxide Nanoparticles

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Improved paramagnetic chelate for molecular imaging with MRI

Cited by 42 publications

References 15 publications

Imaging of Vx‐2 rabbit tumors with ανβ3‐integrin‐targeted 111In nanoparticles

Imaging of Vx‐2 rabbit tumors with ανβ3‐integrin‐targeted 111In nanoparticles

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

NMR Transversal Relaxivity of Suspensions of Lanthanide Oxide Nanoparticles

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Product

Resources

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Imaging of Vx‐2 rabbit tumors with α_νβ₃‐integrin‐targeted ¹¹¹In nanoparticles

Imaging of Vx‐2 rabbit tumors with α_νβ₃‐integrin‐targeted ¹¹¹In nanoparticles