Magnetically-labeled sensitized splenocytes to identify glioma by MRI: a preliminary study.

This study investigated the feasibility of imaging the migration and incorporation of magnetically-labeled sensitized splenocytes in an experimental 9L glioma brain tumor model. Splenocytes collected from tumor-bearing (sensitized splenocytes) or control (nonsensitized splenocytes) host rats were analyzed to determine the population of different cells, labeled with ferumoxides-protamine sulfate (FePro) and injected intravenously to recipient rats (N=4, for each group) bearing intracranial 9L tumors. Day 3 postinjection of splenocytes multiecho T2*-weighted and three-dimensional (3D) gradient echo MRI were obtained using a 7 Tesla MR system. R2* (1/T2*) maps were created from the T2*-weighted images. Signal intensities (SIs) and R2* values in the tumors and contralateral brain were determined by hand drawn regions of interest (ROIs). Brain sections were stained for the evidence of administered cells. Both 3D and T2*-weighted MRI showed low signal intensity areas in and around the tumors in rats that received labeled sensitized splenocytes. Prussian blue (PB), CD45- and CD8-positive cells were present in areas at the corresponding sites of low signal intensities seen on MRI. Rats that received labeled nonsensitized splenocytes did not show low signal intensity areas or PB positive cells in or around the implanted tumors. In conclusion, the immunogenic reaction can be exploited to delineate recurrent glioma using MRI following systemically delivered magnetically labeled sensitized splenocytes or T-cells.     

MRI assessment of the intra‐carotid route for macrophage delivery after transient cerebral ischemia

The broad aim underlying the present research was to investigate the distribution and homing of bone marrow‐derived macrophages in a rodent model of transient middle cerebral artery occlusion using MRI and ultrasmall superparamagnetic iron oxide (USPIO) to magnetically label bone marrow‐derived macrophages. The specific aim was to assess the intra‐carotid infusion route for bone marrow‐derived macrophage delivery at reperfusion. Fifteen Sprague–Dawley rats sustained 1 h of middle cerebral artery occlusion. USPIO‐labeled bone marrow‐derived macrophages were slowly injected for 5 min immediately after reperfusion in ischemic animals (n = 7), 1 h after the end of surgery in sham animals (n = 5) and very shortly after anesthesia in healthy animals (n = 3). Multiparametric MRI was performed at day 0, just after cell administration, and repeated at day 1. Immunohistological analysis included Prussian blue for iron detection and rat endothelial cell antigen‐1 for endothelium visualization. Intra‐carotid cell delivery brought a large number of cells to the ipsilateral hemisphere of the brain, as seen on both MRI and immunohistology. However, it was associated with high mortality (50%). The study of sham animals demonstrated that intra‐carotid cell delivery could induce ischemic lesions and may thus favor additional brain damage. The present study highlights severe drawbacks to the intra‐carotid delivery of macrophages at the time of reperfusion in this rodent model of transient cerebral ischemia. Multiparametric MRI appears to be a method of choice to monitor longitudinally the effects of cell infusion, allowing the assessment of both cell fate with the help of magnetic labeling and of potential tissue damage. Copyright © 2012 John Wiley & Sons, Ltd.     

USEFULNESS OF POWER DOPPLER ULTRASONOGRAPHY AND SUPERPARAMAGNETIC IRON OXIDE ENHANCED MAGNETIC RESONANCE IMAGING FOR DIAGNOSIS OF FOCAL NODULAR HYPERPLASIA OF THE LIVER AFTER TREATMENT OF NEUROBLASTOMA

Focal nodular hyperplasia (FNH) of the liver is rare in children, and it is usually diagnosed through a biopsy of the liver or hepatectomy. The authors report a case of a 10-year-old girl with multiple focal nodular hyperplasia lesions of the liver after the completion of tumor therapy for advanced neuroblastoma, and review the usefulness of the combination of power Doppler ultrasonography (US) and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI) for the diagnosis of FNH without a biopsy of the liver or hepatectomy.     

Epidermoid cyst in intrapancreatic accessory spleen: A systematic review

Background/Objectives

Due to its rarity, epidermoid cyst in intrapancreatic accessory spleen (ECIPAS) is still a diagnostic dilemma during clinical practice. The aim of this review was to summarize the epidemiologic features and management of ECIPAS.

顺磁性铁纳米粒促进人淋巴细胞对乳腺癌细胞的体外杀伤

 目的 探索顺磁性氧化铁纳米颗粒是否能调节由肿瘤裂解蛋白所诱发的针对人乳腺癌细胞(MCF-7)的抗肿瘤免疫反应。方法 将纳米铁颗粒与肿瘤裂解蛋白进行共价连接形成纳米铁-蛋白复合物,用裂解蛋白、纳米铁、纳米铁-蛋白复合物分别刺激人外周血单个核细胞（PBMC）,再将刺激后的PBMC与MCF-7细胞相混合,用MTS方法检测对肿瘤细胞的杀伤率。结果 纳米铁能与60%的肿瘤裂解蛋白相连接,并形成较大的纳米颗粒。与单纯的肿瘤蛋白相比,纳米铁-肿瘤蛋白的复合物能够显著提升PBMC对MCF-7细胞的杀伤,而纳米铁本身对MCF-7无直接杀伤作用。结论 纳米铁-肿瘤蛋白的复合物能够显著增强PBMC在体外杀伤人乳腺癌细胞的能力。     

Emerging applications for ferumoxytol as a contrast agent in MRI

Ferumoxytol is an ultrasmall superparamagnetic iron oxide (USPIO) agent initially approved by the Food and Drug Administration (FDA) as an iron replacement therapy for patients with anemia due to chronic renal failure. Recently, ferumoxytol has been investigated extensively as an intravenous contrast agent in magnetic resonance imaging (MRI). Since it causes regional T₁ and T₂* shortening in vivo, conventional pulse sequences can be used following ferumoxytol administration to demonstrate signal enhancement or loss. Ferumoxytol can be administered as a rapid bolus and has a long intravascular half‐life on the order of 14–15 hours, making it a potentially useful agent for vascular and perfusion‐weighted MRI. In comparison to other USPIOs, ferumoxytol is less limited by allergic and idiosyncratic reactions. Furthermore, since ferumoxytol is an iron‐based agent with no potential for causing nephrogenic systemic fibrosis, it may be useful as an alternative to gadolinium‐based contrast agents in patients with compromised renal function. Ferumoxytol is ultimately taken up by macrophages/the reticuloendothelial system in the liver, spleen, and lymph nodes, and this uptake mechanism is being explored as a novel imaging technique for vascular lesions, tumors, and lymph nodes. This article reviews the properties of ferumoxytol relevant to MRI as well as many of the uses for the agent currently under investigation. J. Magn. Reson. Imaging 2015;41:884–898 . © 2014 Wiley Periodicals, Inc .     

Iron-Oxide Nanocluster Labeling of Clostridium novyi-NT Spores for MR Imaging–Monitored Locoregional Delivery to Liver Tumors in Rat and Rabbit Models

PurposeTo label Clostridium novyi-NT spores (C. novyi-NT) with iron oxide nanoclusters and track distribution of bacteria during magnetic resonance (MR) imaging-monitored locoregional delivery to liver tumors using intratumoral injection or intra-arterial transcatheter infusion.Materials and MethodsVegetative state C. novyi-NT were labeled with iron oxide particles followed by induction of sporulation. Labeling was confirmed with fluorescence microscopy and transmission electron microscopy (TEM). T2 and T2* relaxation times for magnetic clusters and magnetic microspheres were determined using 7T and 1.5T MR imaging scanners. In vitro assays compared labeled bacteria viability and oncolytic potential to unlabeled controls. Labeled spores were either directly injected into N1-S1 rodent liver tumors (n = 24) or selectively infused via the hepatic artery in rabbits with VX2 liver tumors (n = 3). Hematoxylin-eosin, Prussian blue, and gram staining were performed. Statistical comparison methods included paired t-test and ANOVA.ResultsBoth fluorescence microscopy and TEM studies confirmed presence of iron oxide labels within the bacterial spores. Phantom studies demonstrated that the synthesized nanoclusters produce R2 relaxivities comparable to clinical agents. Labeling had no significant impact on overall growth or oncolytic properties (P >.05). Tumor signal-to-noise ratio (SNR) decreased significantly following intratumoral injection and intra-arterial infusion of labeled spores (P <.05). Prussian blue and gram staining confirmed spore delivery.ConclusionsC. novyi-NT spores can be internally labeled with iron oxide nanoparticles to visualize distribution with MR imaging during locoregional bacteriolytic therapy involving direct injection or intra-arterial transcatheter infusion.     

Assessing the selective therapeutic efficacy of superparamagnetic erlotinib nanoparticles in lung cancer by using quantitative magnetic resonance imaging and a nuclear factor kappa-B reporter gene system

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used as the first-line treatment for advanced NSCLC; however, the efficacy of drug delivery remains unknown. Hence, we successfully developed erlotinib-conjugated iron oxide nanoparticles (FeDC-E NPs) as theranostic probe that can potentially provide a new avenue for monitoring drug delivering through noninvasive magnetic resonance imaging. MRI ΔR2* relaxivity measurements offer an opportunity to quantitatively evaluate the uptake of FeDC-E NPs at cellular and tumoral levels. Additionally, NF-κB reporter gene system provides NF-κB activation status monitoring to validate the therapeutic efficiency of FeDC-E NPs. FeDC-E NPs not only inhibit the tumor growth and NF-κB-modulated antiapoptotic mechanism but also trigger extrinsic and intrinsic apoptotic pathways. Taken together, dual functional FeDC-E NPs offer diagnostic and therapeutic benefits against lung cancers, indicating that our presented probe could be applied in clinical.     

High-content analysis for mitophagy response to nanoparticles: A potential sensitive biomarker for nanosafety assessment

Mitophagy, a selective autophagy of mitochondria, clears up damaged mitochondria to maintain cell homeostasis. We performed high-content analysis (HCA) to detect the increase of PINK1, an essential protein controlling mitophagy, in hepatic cells treated with several nanoparticles (NPs). PINK1 immunofluorescence-based HCA was more sensitive than assays and detections for cell viability and mitochondrial functions. Of which, superparamagnetic iron oxide (SPIO)-NPs or graphene oxide-quantum dots (GO-QDs) was selected as representatives for positive or negative inducer of mitophagy. SPIO-NPs, but not GO-QDs, activated PINK1-dependent mitophagy as demonstrated by recruitment of PARKIN to mitochondria and degradation of injured mitochondria. SPIO-NPs caused the loss of mitochondrial membrane potential, decrease in ATP, and increase in mitochondrial reactive oxide species and Ca²⁺. Blocking mitophagy with PARKIN siRNA aggravated the cytotoxicity of SPIO-NPs. Taken together, PINK1 immunofluorescence-based HCA is considered to be an early, sensitive, and reliable approach to evaluate the bioimpacts of NPs.     

A novel bubble-forming material for preparing hydrophobic-agent-loaded bubbles with theranostic functionality

In the present study, a new bubble-forming material (carboxymethyl hexanoyl chitosan, CHC), together with superparamagnetic iron oxide (SPIO) nanoparticles, was employed to prepare image-guided bubbles for efficiently encapsulating and delivering hydrophobic agents to kill tumor cells. The results showed that CHC could be used for preparing not only micronized bubbles (CHC/SPIO MBs) to exhibit ultrasound imaging functionality but also nanosized bubbles (CHC/SPIO NBs) to exhibit magnetic resonance T₂ image contrast. It was found that the amounts of SPIO nanoparticles and hexane during preparation process were the key factors to obtaining CHC/SPIO NBs. Most importantly, under in vitro cell culture conditions with the same amount of camptothecin (CPT) and therapeutic sonication, CPT-loaded CHC/SPIO NBs demonstrated more significant transcellular delivery and cytotoxicity than free CPT. Subsequently, an intratumoral injection was proposed for the in vivo administration of hydrophobic-agent-loaded CHC/SPIO NBs. After injection, the distribution of a hydrophobic dye (DiR, an agent with near-infrared (NIR) fluorescence used as a model drug) released from the CHC/SPIO NBs was tracked by an NIR imaging technique. A significant tumor-specific accumulation was observed in the mouse that received the DiR-loaded CHC/SPIO NBs; the same was not observed in the mouse that received the free dye (without incorporating with CHC/SPIO NBs). It is expected, in the future, both the dose of the therapeutic agent administered and its side effects can be significantly lowered by using novel CHC/SPIO NBs together with local delivery (intratumoral injection), targeted imaging and enhanced cellular uptake of the drug.