Biomedical subjects

R Weissleder

Publications and source records attributed to R Weissleder.

At least 181 records · Page 10Linked to original sources

PubMedDate not supplied

Contrast enhancement in experimental radiation-induced liver injury: comparison of hepatocellular and reticuloendothelial particulate contrast agents.

We compared the liver enhancement of two superparamagnetic agents, polycrystalline iron oxide nanoparticles (PION) and PION coated with asialofetuin (ASF), in an experimental model of focal radiation-induced hepatitis. PION, a reticuloendothelial system-directed agent, and PION-ASF, a hepatocellular-directed agent, were compared for time-dependent liver enhancement in an experimental model of radiation-induced liver injury. Using the reticuloendothelial system (RES)-directed PION, the normal, nonirradiated portion of the liver decreased in signal intensity (SI) with a mean negative enhancement of -66% +/- 4, whereas the irradiated portion (60 Gy, 3 days before imaging) of the liver decreased in SI by -24% +/- 2, significantly less (P <.05). SI changes in irradiated liver tissue using PION were dose-dependent, being more pronounced with lower radiation exposure. The difference in SI changes induced by PION-ASF between irradiated and nonirradiated liver was not statistically different, but SI decreased with a mean negative enhancement of -80% +/- 2. The RES-directed PION is more sensitive for the detection of radiation-induced hepatitis than is the hepatocyte-directed PION-ASF. The insensitivity of PION-ASF enhancement for diffuse liver injury may be clinically advantageous for detecting focal lesions in the presence of diffuse hepatic injury.

Animals↗

PubMedDate not supplied

Magnetically labeled cells can be detected by MR imaging.

To determine the feasibility of MR imaging of magnetically labeled cells, different cell lines were labeled with monocrystalline iron oxide (MION) particles. Phantoms containing MION labeled cells were then assembled and imaged by MR at 1.5 T using T1-weighted and T2-weighted pulse sequences. MION uptake ranged from 8.5 x 10(4) to 2.9 x 10(5) particles/cell for tumor cells (9L and LX1, respectively) to 1.5 x 10(6) to 4.8 x 10(8) particles/cell for "professional phagocytes" (J774 and peritoneal macrophages, respectively). On the T1-weighted images, cell-internalized MION appeared hyperintense relative to agar and similar to MION in aqueous solution. On T2-weighted images, signal intensity varied according to concentration of MION within cells. Cell-internalized MION caused similar MR signal changes of cells as did free MION; however, at a dose that was an order of magnitude lower, depending on the pulse sequence used. The detectability of MION within cells was approximately 2 ng Fe, which corresponded to 10(5) tumor cells/well or 5 x 10(3) macrophages/well. We conclude that a variety of cells can be efficiently labeled with MION by simple incubation. Intracellular labeling may be used for MR imaging of in vivo cell tracking.

Contrast Media↗

PubMedDate not supplied

Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages.

Although several dextran-coated iron oxide preparations are in preclinical and clinical use, little is known about the mechanism of uptake into cells. As these particles have been shown to accumulate in macrophages and tumor cells, we performed cellular uptake and inhibition studies with a prototypical monocrystalline iron oxide nanoparticle (MION). MION particles were labeled with fluorescein isothiocyanate or radioiodinated and purified by gel permeation chromatography. Two preparations of MION particles were used in cell experiments: nontreated MION and plasma-opsonized MION purified by gradient density purification. As determined by immunoblotting, opsonization resulted in C3, vitronectin, and fibronectin association with MION. Incubation of cells with fluorescent MION showed active uptake of particles in macrophages both before and after opsonization. In C6 tumor cells, however, intracellular MION was only detectable in dividing cells. Quantitatively, 125I-labeled MION was internalized into cells with uptake values ranging from 17 ng (in 9L gliosarcoma) to 970 ng iron per million cells for peritoneal macrophages. Opsonization increased MION uptake into macrophages sixfold, whereas it increased the uptake in C6 tumor cells only twofold. Results from uptake inhibition assay suggest that cellular uptake of nonopsonized (dextran-coated) MION particles is mediated by fluid-phase endocytosis, whereas receptor-mediated endocytosis is presumably responsible for the uptake of opsonized (protein-coated) particles.

Animals↗

PubMedDate not supplied

Preclinical assessment of hepatocyte-targeted MR contrast agents in stable human liver cell cultures.

Much effort has been expended in the search for hepatocyte-specific MR contrast agents to improve the detection and characterization of liver tumors. The purpose of this study was to establish human hepatocyte cell cultures to preclinically assess hepatocyte-targeted magnetopharmaceuticals. Cultured human hepatocytes were sandwiched between two layers of collagen preserving both hepatocyte function and morphology over prolonged period of time. Cultures (n = 37) were subsequently used to test different fluorescinated MR contrast agents. Plain and rhodaminated monocrystalline iron oxide particles (MION and MION-rh) and asialoglycoprotein-receptor-specific rhodaminated asialofetuin coupled to MION (MION-ASF-rh) were prepared. Competition experiments of these agents were performed with D(+)-galactose to study the specificity of galactose-mediated cell uptake. To assess the impact of cell integrity on cell uptake, functional experiments with CCl4 were performed. Normal cell cultures showed significantly higher fluorescence light emission after incubation with hepatocyte-directed ASF-MION-rh than after incubation with MION-rh. Competition experiments of ASF-MION-rh with galactose showed a dose-dependent decrease of calibrated fluorescence light emission. Cell cultures treated with CCl4 demonstrated a dose-dependent significant reduction of calibrated fluorescence light emission, indicating reduced uptake of ASF-MION-rh. Our data demonstrate that stable human hepatocyte cell cultures can be used to preclinically assess novel magnetopharmaceuticals. Different contrast agents may be directly compared to each other and may accelerate their preclinical design. Because the assay can be applied to cells from any species, it may represent an ideal test system before clinical trials of new cell-directed MR contrast agents.

Asialoglycoprotein Receptor↗

PubMedDate not supplied

MRI of hepatic lymphoma.

Thirteen patients with biopsy proven hepatic lymphoma (2 Hodgkin, 11 Non-Hodgkin) and a control group of 15 patients with hepatic metastases were analyzed quantitatively and qualitatively by MRI. Focal hepatic lymphoma was most reliably detected (eight of eight patients) and appeared hypointense relative to liver on T1 weighted (CNR - 7.4 +/- 2.3) and hyperintense on T2 weighted (CNR + 8.4 +/- 2.9) images. The mean T1 and T2 relaxation times of focal hepatic lymphoma (T1 = 832 +/- 234 msec, T2 = 84 +/- 16 ms) differed significantly from adjacent non-tumorous liver (T1 = 420 +/- 121 ms, T2 = 51 +/- 9 ms; p less than 0.05), however CNR values and relaxation times were similar to those of hepatic metastases. Diffuse hepatic lymphoma (microscopic periportal infiltration) was undetectable by MRI in three patients by either morphologic features or quantitative criteria. A mixed pattern of hepatic lymphoma (focal lesions and diffuse infiltration) showed focal areas of slightly decreased signal intensity on T1 weighted images (CNR = -1.7 +/- 0.4) while T2 weighted images revealed multiple regions of focal hyperintensity (CNR = +13.3 +/- 8.4) superimposed on a diffusely hyperintense liver. Our experience demonstrates that either T1 or T2 weighted techniques are useful in detecting focal and that T2 weighted techniques are useful in detecting mixed hepatic lymphoma. Conventional image derived relaxation time measurements and quantitative parameters were of no additional diagnostic value.

Adenocarcinoma↗

PubMedDate not supplied

Cholecystitis: diagnosis by MR imaging.

Morphologic features which allow the diagnosis of acute cholecystitis by ultrasound and CT have now been observed by MR. When present, thickening of the gallbladder wall, intramural abscess, pericholecystic fluid, and the presence of gallstones may be more specific than MR characterization of gallbladder bile.

Aged↗

PubMedDate not supplied

Hepatic metastases: rat models for imaging research.

Improved rat liver tumor models with solitary or multiple metastatic tumors were developed for radiological imaging research. Unlike previous studies which employed trocar inoculation of tumor fragments, an enzymatically disaggregated cell suspension of mammary cancer was injected by fine needle either directly into the liver to produce solitary cancer nodules, or indirectly via the spleen or mesenteric vein to produce multiple liver metastases. Tumor size was proportional to the time elapsed after implantation. The operative mortality of direct liver, splenic parenchymal, and mesenteric inoculations were 8%, 4%, and 27%, respectively. MR tissue characteristics, image contrast, and pharmaceutical enhancement of these tumors closely resembles human hepatic metastases. The availability of reproducible, inexpensive animal models of metastatic cancer allows efficient evaluation of new liver imaging techniques.

Adenocarcinoma↗

PubMedDate not supplied

Improvement of MRI probes to allow efficient detection of gene expression.

Recently, it has been demonstrated that magnetic resonance imaging (MRI) utilizing monocrystalline iron oxide nanoparticles (MIONs) targeted to an engineered transferrin receptor enables imaging of gene expression. However, the relatively high doses of iron oxides used indicated the need for improved MR imaging probes to monitor changes in gene expression in vivo. Using alternative conjugation chemistries to link targeting ligands and iron oxide nanoparticles, we present the development and characterization as well as improved receptor binding and MRI detection of a novel imaging probe. Iron oxide nanoparticles with a cross-linked dextran coat were conjugated to transferrin (Tf) through the linker molecule N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) to yield Tf-S-S-CLIO. The characteristics of this conjugate were evaluated in comparison to Tf-MION and Tf-CLIO generated by oxidative activation of the dextran-coat with subsequent reduction of Schiff's base. SPDP conjugation allowed approximately a 4-fold increase in the number of Tf molecules attached per iron oxide nanoparticle and resulted in a more than 10-fold improvement of binding and uptake by cells. This translated into an imaging probe that was 16 times better for imaging gene expression in a cellular MRI assay. This novel probe for MRI may substantially increase the sensitivity for the detection of endogenous or genetically induced transferrin receptor expression in small numbers of cells and may significantly reduce the imaging dose from over 100 mg/kg to doses of iron oxides that are currently used in clinical imaging.

Animals↗

PubMedDate not supplied

Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging.

Angiogenesis is a critical step in tumor development and more than 25 angiogenesis inhibitors are currently in clinical trials. Noninvasive in vivo imaging of angiogenesis represents a unique opportunity of repeatedly quantitating microvascular parameters prior to and during anti-angiogenic treatments. While several imaging tracers have been proposed for MR and nuclear imaging, there does not exist any consensus of what constitutes an ideal size of an imaging agent. A series of synthetic pegylated DOTA derivatized graft copolymers (30, 60, 120 kDa) were synthesized and their in vivo behavior tested in two breast cancer models differing in vascular endothelial growth factor (VEGF) expression. Polymers were labeled with different lanthanides (Eu, Gd, Dy) and absolute blood and tumor concentrations were determined by ICP-AES measurements. DOTA and the 30 kDa polymers underwent renal clearance resulting in low plasma levels. Slow leakage across neovasculature into tumor interstitium was clearly dependent on the molecular mass of all tested agents in MCF-7 tumors. However, a cutoff was observed with minimal extravasation occurring at and above 120 kDa in well differentiated MCF-7 tumors. VEGF overexpression caused detectable differences in extravasation of all polymers, including the 120 kDa compound. We conclude that large molecular weight contrast agents with a molecular mass of <120 kDa extravasate from experimental tumor neovasculature and may not be an accurate marker for measuring true blood volume fractions when in vivo imaging is performed in the steady state.

Animals↗

PubMedDate not supplied

Uptake and metabolism of a dual fluorochrome Tat-nanoparticle in HeLa cells.

The ability to use magnetic nanoparticles for cell tracking, or for the delivery of nanoparticle-based therapeutic agents, requires a detailed understanding of probe metabolism and transport. Here we report on the development and metabolism of a dual fluorochrome version of our tat-CLIO nanoparticle termed Tat(FITC)-Cy3.5-CLIO. The nanoparticle features an FITC label on the tat peptide and a Cy3.5 dye directly attached to the cross-linked coating of dextran. This nanoparticle was rapidly internalized by HeLa cells, labeling 100% of cells in 45 min, with the amount of label per cell increasing linearly with time up to 3 h. Cells loaded with nanoparticles for 1 h retained 40-60% of their FITC and Cy3.5 labels over a period of 72 h in label-free media. Over a period of 144 h, or approximately 3.5 cell divisions, the T2 spin-spin relaxation time of cells was not significantly changed, indicating retention of the iron oxide among the dividing cell population. Using confocal microscopy and unfixed cells, both dyes were nuclear and perinuclear (broadly cytoplasmic) after Tat(FITC)-Cy3.5-CLIO labeling. Implications of the rapid labeling and slow excretion of the Tat(FITC)-Cy3.5-CLIO nanoparticle are discussed for cell tracking and drug delivery applications.

Carbohydrate Sequence↗

PubMedDate not supplied

An adduct of cis-diamminedichloroplatinum(II) and poly(ethylene glycol)poly(L-lysine)-succinate: synthesis and cytotoxic properties.

A noncovalent adduct of the antineoplastic drug cis-diamminedichloroplatinum (cDDP) and a biocompatible graft copolymer of poly(L-lysine) and methylpoly(ethylene glycol) succinate is described. Upon incubation of cDDP with [O-methylpoly(ethylene glycol)-O'-succinyl]-N- epsilon-poly(L-lysine)n-N-epsilon-succinate, n = 250-270, highly soluble, long circulating adducts were formed which contained 4.3% of platinum by weight. Approximately 60% of the polymer-associated drug was released during dialysis against saline or serum albumin containing saline, with a half-time of release of 63 h. The adducts showed a pronounced antineoplastic effect in BT-20 human adenocarcinoma cell cultures. In cell proliferation assays, the concentration of half-inhibition of [3H]thymidine uptake was 0.9 +/- 0.2 microM for the drug-copolymer adduct compared to 0.3 +/- 0.1 microM for free cDDP. The adduct showed a long blood half-life (ca. 14 h in rats) and accumulated in experimental mammary adenocarcinomas at 2.5-3.5% injected dose per gram of tissue. A control adduct of cDDP with the backbone portion of the copolymer, poly(L-lysine)-N-epsilon-succinate, had a short half-life in the bloodstream (ca. 30 min) and low accumulation (0.5% injected dose per gram) in tumor. A dual therapeutical effect of methylpoly(ethylene glycol)succinylpoly(L-lysine)-succinate as a carrier of cDDP is suggested: (1) as a carrier for systemic release of the active drug from the macromolecule while it circulates in the bloodstream and (2) as a carrier for on-site delivery which results from the release of the drug in the tumor as a consequence of accumulation of the copolymer in the tumor.

Adenocarcinoma↗

PubMedDate not supplied

Magnetically labeled secretin retains receptor affinity to pancreas acinar cells.

Previously, we have developed a colloidal dextran-stabilized monocrystalline iron oxide nanocompound (MION-46) as a magnetic label for magnetic resonance imaging (MRI). In an effort to use this magnetic label to visualize pancreatic receptor function by MRI in vivo, we investigated the potential of secretin as a vector molecule. Secretin receptors, abundant on exocrine pancreas cells, recognize secretin through its amidated carboxyl terminal. In order to conjugate secretin to MION, we utilized the specific interaction between biotin and streptavidin, since direct conjugation of human secretin to MION has previously resulted in low yields and low affinity of the conjugate (unpublished results). Initially, we biotinylated the N-terminal primary amino group of secretin (60% yield). In a separate step, streptavidin (SA) was immobilized onto the surface dextran molecules of MION (79% yield) by reductive amination. Each secretin molecule was conjugated to one biotin molecule and each MION particle to an average of two SA molecules. The biotinylated secretin was then conjugated to MION through the biotin-streptavidin interaction (90% yield). The secretin-biotin-streptavidin-MION construct thus contained approximately two secretin molecules per MION. An in vitro competitive binding assay of pancreatic acinar cells demonstrated that the magnetically labeled secretin retained affinity to the secretin receptors. In vivo distribution studies in rats showed a significantly higher pancreatic accumulation of the secretin-biotin-streptavidin-MION construct as compared to the control group that had received unmodified MION. Our data indicate that bioactive peptides can be attached to dextran-coated iron oxide particles through the biotin-streptavidin interaction while retaining receptor affinity. Such target-specific agents have potential use in MR imaging to probe for a variety of receptor systems.

Animals↗

PubMedDate not supplied

Antibody-mediated versus nontargeted delivery in a human small cell lung carcinoma model.

The uptake of macromolecular agents in tumor cells (LX-1, human small cell lung carcinoma) and in corresponding tumor xenografts was compared in a parallel study utilizing a long-circulating biocompatible graft copolymer, MPEGs-PL-DTPA [Bogdanov, A., Jr., et al. (1995) Adv. Drug Delivery Rev. 16, 335-348; Bogdanov, A., Jr., et al. (1996) Bioconjugate Chem. 7, 144-149] and a tumor-specific chimeric monoclonal antibody, BR96 [Hellstrom, I., et al. (1990) Cancer Res. 50, 2183-2190; Garrigues, J., et al. (1993) Am. J. Pathol. 142, 607-622]. Covalent grafted conjugates of methoxy-(polyethylene glycol)succinate and polylysine and BR96 were modified with DTPA, biotinyl, or rhodamine-X-residues. Using radionuclide and fluorescent labeled derivatives of the copolymer and the antibody, we established that (1) the copolymer does not associate with the plasma membrane in N-ethylmaleimide-treated cells and is slowly internalized by live cells at 37 degrees C; (2) the antibody binds rapidly to the surface of LX-1 cells and shows active internalization in vesicles with a subsequent slow decrease in the cell-associated antibody concentration; (3) LX-1 cells bear more than 1 million BR96 binding sites/cell (with an apparent Kd of 4.5 x 10[-7] M); and (4) intravesicular fluorescence intensity in LX-1 cells was linearly dependent on copolymer concentration, suggesting fluid phase endocytosis. Tumor localization by nuclear imaging, biodistribution, microdistribution by histology, and determination of tumor cell fraction uptake was performed in LX-1 tumor xenografts. In vivo study showed that MPEGs-PL-DTPA progressively accumulates in the tumor, yielding from 2.8+/-1.5% injected dose per gram of tissue (ID/g) at 24 h to 5.2+/-1.7% ID/g of tissue at 48 h. The antibody accumulation peaked at 24 h (6.0+/-3.2% ID/g) and decreased thereafter. We determined that at 24 h 43.9+/-11.29% of the polymer accumulated in the tumor was associated with tumor cell fraction with the remainder of the accumulated dose localized in the interstitium. Accumulation of the biotinylated graft copolymer and the antibody in LX-1 xenografts and their uptake in cells were confirmed by histology using avidin-peroxidase staining. Our study demonstrates that, although BR96 is highly specific in vitro, tumoral drug delivery in vivo can be equally high with long-circulating graft copolymers because of slow extravasation at the tumor site.

Animals↗

PubMedDate not supplied

High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates.

A biocompatible, dextran coated superparamagnetic iron oxide particle was derivatized with a peptide sequence from the HIV-tat protein to improve intracellular magnetic labeling of different target cells. The conjugate had a mean particle size of 41 nm and contained an average of 6.7 tat peptides. Derivatized particles were internalized into lymphocytes over 100-fold more efficiently than nonmodified particles, resulting in up to 12.7 x 10(6) particles/cell. Internalized particles localized in cytoplasm and nuclear compartments as demonstrated by fluorescence microscopy and immunohistochemistry. Labeled cells were highly magnetic, were detectable by NMR imaging, and could be retained on magnetic separation columns. The described method has potential applications for in vivo tracking of magnetically labeled cells by MR imaging and for recovering intracellularly labeled cells from organs.

Amino Acid Sequence↗

PubMedDate not supplied

Preparation of a cathepsin D sensitive near-infrared fluorescence probe for imaging.

A variety of proteases are overexpressed or activated during pathogenesis and represent important targets for therapeutic drugs. We have previously shown that optical imaging probes sensitive in the near-infrared fluorescence (NIRF) spectrum can be used for in vivo imaging of enzyme activity. In the current study, we show that these probes can be designed with specificity for specific enzymes, for example, cathepsin D which is known to be overexpressed in many tumors. A NIR cyanine fluorochrome served as the optical reporter and was attached to the amino terminal of an 11 amino acid peptide sequence with specificity for cathepsin D. The peptides were subsequently attached to a synthetic graft copolymer for efficient tumoral delivery. The close spatial proximity of the multiple fluorochromes resulted in quenching of fluorescence in the bound state. A 350-fold signal amplification was observed post cleavage during in vitro testing. Cell culture experiments using a rodent tumor cell line stably transfected with human cathepsin D confirmed enzyme specific activation within cells. This sequence but not a scrambled control sequence showed enzyme specificity in vitro. We conclude that activatable NIRF optical probes can be synthesized to potentially probe for specific enzymes in living organisms.

Animals↗

PubMedDate not supplied

Macrocyclic chelators with paramagnetic cations are internalized into mammalian cells via a HIV-tat derived membrane translocation peptide.

A major obstacle to using paramagnetic MR contrast agents for in vivo cell tracking or molecular sensing is their generally low cellular uptake. In this study, we show that a paramagnetically labeled DOTA chelator derivatized with a 13-mer HIV-tat peptide is efficiently internalized into mammalian cells. Intracellular concentrations were attained that were readily detectable by MR imaging using both gadolinium and dysprosium chelates. Using this paradigm, it should be feasible to internalize a variety of chemically different agents into mammalian cells.

Amino Acid Sequence↗

PubMedDate not supplied

Detection of spontaneous schwannomas by MRI in a transgenic murine model of neurofibromatosis type 2.

Spontaneous schwannomas were detected by magnetic resonance imaging (MRI) in a transgenic murine model of neurofibromatosis type 2 (NF2) expressing a dominant mutant form of merlin under the Schwann cell-specific P0 promoter. Approximately 85% of the investigated mice showed putative tumors by 24 months of age. Specifically, 21% of the mice showed tumors in the intercostal muscles, 14% in the limb muscles, 7% in the spinal cord and spinal ganglia, 7% in the external ear, 14% in the muscle of the abdominal region, and 7% in the intestine; 66% of the female mice had uterine tumors. Multiple tumors were detected by MRI in 21% of mice. The tumors were isointense with muscle by T1-weighted MRI, showed strong enhancement following administration of gadolinium-DTPA, and were markedly hyperintense by T2-weighted MRI, all hallmarks of the clinical manifestation. Hematoxylin and eosin staining and immunohistochemistry indicated that the tumors consisted of schwannomas and Schwann cell hyperplasias. The lesions stained positively for S-100 protein and a marker antigen for the mutated transgenic NF2 protein, confirming that the imaged tumors and areas of hyperplasia were of Schwann cell origin and expressed the mutated NF2 protein. Tumors were highly infectable with a recombinant herpes simplex virus type 1 vector, hrR3, which contains the reporter gene, lacZ. The ability to develop schwannoma growth with a noninvasive imaging technique will allow assessment of therapeutic interventions.

Animals↗

PubMedDate not supplied

Splenic imaging with ultrasmall superparamagnetic iron oxide ferumoxtran-10 (AMI-7227): preliminary observations.

PURPOSE: Ferumoxtran-10 (ultrasmall superparamagnetic iron oxide; Combidex, AMI-7227) is a long-circulating MR contrast agent with reticuloendothelial uptake known to enhance tissue T1 and T2 relaxation rates. The purpose of this study was to assess the effect of ferumoxtran-10-enhanced MRI in evaluating focal splenic lesions. METHOD: Eighteen patients underwent MR evaluation of the spleen. Two of these patients with exophytic normal splenic tissue (splenules) and 13 of these patients with 24 focal splenic lesions (7 cysts, 2 hemangiomas, 7 metastases, 1 infarct, 7 lymphoma) were assessed by T1-weighted gradient echo and T2-weighted fast SE MRI following intravenous administration of ferumoxtran-10 (1.1 mg of Fe/kg). Qualitative analysis involving improved lesion detection and/or characterization, additional information from postcontrast images affecting staging, and patient management was performed. Quantitative measurements of lesion-to-spleen contrast-to-noise ratio were also performed. RESULTS: Additional information was provided by ferumoxtran-10-enhanced images in 15 of 18 patients. In 8 of 15 (53%) patients, improved lesion detection (i.e., number of lesions) was obtained on contrast-enhanced images. Improved lesion visualization (i.e., conspicuity) was noted in 11 of 15 (73%) of patients. In 10 of 15 (67%) patients, postcontrast imaging provided additional information leading to lesion characterization. Staging of disease and patient management were affected in 5 of 15 (33%) and 6 of 15 (40%) patients, respectively. CONCLUSION: Ferumoxtran-10 is a promising contrast agent for the evaluation of focal splenic lesions.

Adult↗