In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging

Wu, Yuanhao; Muldoon, Leslie L.; Várallyay, Csanád; Markwardt, Sheila; Jones, Richard E.; Neuwelt, Edward A.

doi:10.1152/ajpcell.00215.2007

Cited by 67 publications

(66 citation statements)

References 46 publications

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“…The NP of SPIO and NF preparations were different in surface morphology, physical characteristics (density), surface charge, PEG concentration and functional modification which may affect the PK. The cellular and tissue uptake was effected by several characteristics of the nanoparticles e.g., particle size, coatings, and charge as demonstrated by Wu et al, (30). In another study surface properties had a larger impact on cellular uptake of SPIO particles rather than particle size (31).…”

Section: Discussionmentioning

confidence: 84%

“…Each purified RINP was a dark brown, homogeneous suspension and remained at the origin of PAGE. The RINPs (20,30 and 100 nm) shown in figure 2A, by Coomassie lanes 1− 3 and radioactivity in lanes 4 −6, did not migrate due to the high molecular weight. However, no unbound ChL6 or 111 In-DOTA-ChL6 was observed, corresponding to the control protein in Figure 2A Figure 3 shows the evaluation of the RINP mobility by CAE at 11 min (lanes # 1, 3 and 5) and 45 min (lanes # 2, 4 and 6).…”

Section: Preparation Characterization and Quality Assurance Of Ric mentioning

confidence: 92%

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NanoFerrite Particle Based Radioimmunonanoparticles: Binding Affinity and In Vivo Pharmacokinetics

et al. 2008

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Dextran and PEG coated iron oxide nanoparticles (NP), when suitably modified to enable conjugation with molecular targeting agents, provide opportunities to target cancer cells. Monoclonal Antibodies, scFv, and peptides conjugated to 20-nm NP have been reported to target cancer for imaging and alternating magnetic field (AMF) therapy. The physical characteristics of NP's can affect their in vivo performance. Surface morphology, surface charge density, and particle size are considered important factors that determine pharmacokinetics, toxicity, and biodistribution. New NanoFerrite (NF) particles having improved specific AMF absorption rates and diameters of 30 nm and 100 nm were studied to evaluate the variation in their in vitro and in vivo characteristics in comparison to the previously studied 20 nm Superparamagnetic Iron Oxide (SPIO) NP. SPIO NP 20-nm, NF NP 30-and 100-nm were conjugated to 111 In-DOTA-ChL6, a radioimmunoconjugate. Radioimmunoconjugates were conjugated to NP's using 25μg of RIC/mg of NP by carbodiimide chemistry. The radioimmunonanoparticles (RINP) were purified characterized by PAGE, cellulose acetate electrophoresis (CAE), live cell binding assays, and pharmacokinetics in athymic mice bearing human breast cancer (HBT 3477) xenografts. RINP (2.2 mg) were injected iv and whole body, blood and tissue data were collected at 4, 24, and 48 hours. The preparations used for animal study were >90% monomeric by PAGE and CAE. The immunoreactivity of the RINP was 40−60% compared to 111 In-ChL6. Specific activities of the doses were 20−25μCi/2.2 mg and 6−11μg of MAb/2.2 mg of NP. Mean tumor uptakes (% ID/g ± SD) of each SPIO 20nm, NF 30nm, and 100nm RINP at 48h were 9.00 ± 0.8 (20nm), 3.0 ± 0.3 (30nm), and 4.5 ± 0.8 (100nm) respectively; the ranges of tissue uptakes were liver (16−32 ± 1 − 8), kidney (7.0−15 ± 1) spleen (8−17 ± 3 − 8) lymph nodes 5 − 6 ± 1 −2) and lung (2.0− 4 ± 0.1 − 2). In conclusion, this study demonstrated that 100 nm NF NP could be conjugated to 111 In-MAb so that the resulting RINP had characteristics suitable for AMF therapy. Although 100-nm RINP targeted tumor less than 20-nm SPIO RINP, their heating capacity is typically 6 times greater, suggesting the 100-nm NF RINP could still deliver better therapy with AMF.

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Section: Discussionmentioning

confidence: 84%

Section: Preparation Characterization and Quality Assurance Of Ric mentioning

confidence: 92%

NanoFerrite Particle Based Radioimmunonanoparticles: Binding Affinity and In Vivo Pharmacokinetics

et al. 2008

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“…First, the labeling efficiency of neutrally charged USPIO (Sinerem/Combidex) in monocytes is considered to be rather poor as demonstrated in several in vitro and in vivo studies [18,22,46,47,48]. Conversely, the labeling of circulating leukocytes has been shown to significantly increase after intravenous injection of an SPIO/transfection agent (Feridex/protamine sulfate) complex [48]. Furthermore, monocytes are known to favor the uptake of larger nanoparticles, such as Endorem/Feridex, or charged nanoparticles, such as Resovist [47].…”

Section: Cellular Mri Of Leukocytesmentioning

confidence: 99%

“…Currently, Feraheme is only clinically approved for the treatment of iron deficiency anemia in adult patients with chronic kidney disease. However, several studies have shown that Feraheme can also be employed as a contrast agent for MRI [48,53,54,55]. Another alternative is P904 (Guerbet), 25- to 30-nm iron oxide particles for which phase I clinical trials have been initiated.…”

Section: Cellular Mri Of Leukocytesmentioning

confidence: 99%

Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies

et al. 2012

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Cellular and molecular magnetic resonance imaging (MRI) strategies for studying the spatiotemporal profile of neuroinflammatory processes after stroke are increasingly being explored since the first reports appeared about a decade ago. These strategies most often employ (super)paramagnetic contrast agents, such as (ultra)small particles of iron oxide and gadolinium chelates, for MRI-based detection of specific leukocyte populations or molecular inflammatory markers that are involved in the pathophysiology of stroke or plasticity. In this review we describe achievements, limitations and prospects in the field of cellular and molecular MRI of neuroinflammation in preclinical and clinical stroke. Several studies in rodent stroke models have demonstrated the application of MRI contrast agents for imaging of monocyte infiltration, which served as the foundation for pilot (small-scale proof-of-concept) cellular MRI studies in stroke patients. This may be achieved with isolated cells that are loaded with contrast agent through in vitro incubation prior to systemic administration. Alternatively, superparamagnetic iron oxide particles may be directly injected into the circulation to allow in vivo uptake by phagocytic cells. Both strategies have been successfully employed to measure the spatiotemporal profile of invasion of monocytes in and around cerebral ischemic lesions in experimental stroke models. Molecular MRI studies with target-specific contrast agents have shown the capability for in vivo detection of molecular markers after experimental stroke. For example, (super)paramagnetic micro- or nanoparticles that are functionalized with a ligand (e.g. an antibody) for specific cell adhesion molecules, such as E-selectin and vascular cell adhesion molecule 1 (VCAM-1), can target inflamed, activated endothelium, whose presence can subsequently be detected with MRI. Present applications remain limited as most of the currently available contrast agents provide relatively poor contrast enhancement, which is not easily discriminated from endogenous sources of tissue contrast. Nevertheless, current developments of more efficient particles, such as biocompatible liposomes, micelles and nanoemulsions that can contain high payloads of (super)paramagnetic material as well as other substances, such as dyes and drugs, may open a window of opportunities for promising translational multimodal imaging strategies that enable in vivo assessment of (neuroinflammatory) disease markers, therapeutic targets as well as drug delivery after stroke.

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“…With the nano-scaled sizes and non-toxicity, magnetic nanoparticles are applied to bio-medicine, such as magnetic resonance imaging (MRI) contrast agent [1][2][3][4], drug delivery [5][6][7], cell sorting [8,9], etc. Since 1997, researchers have been proposing to use bio-functionalized magnetic nanoparticles for immunoassay.…”

Section: Introductionmentioning

confidence: 99%

Stability study for magnetic reagent assaying Hb and HbA1c

Hsieh¹,

Chieh

Yang

et al. 2013

Journal of Magnetism and Magnetic Materials

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In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging

Cited by 67 publications

References 46 publications

NanoFerrite Particle Based Radioimmunonanoparticles: Binding Affinity and In Vivo Pharmacokinetics

NanoFerrite Particle Based Radioimmunonanoparticles: Binding Affinity and In Vivo Pharmacokinetics

Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies

Stability study for magnetic reagent assaying Hb and HbA1c

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