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Brett Z Fite, Azadeh Kheirolomoom, Josquin L Foiret, Jai W Seo, Lisa M Mahakian, Elizabeth S Ingham, Sarah M Tam, Alexander D Borowsky, Fitz-Roy E Curry, Katherine W Ferrara
Temperature-sensitive liposomal formulations of chemotherapeutics, such as doxorubicin, can achieve locally high drug concentrations within a tumor and tumor vasculature while maintaining low systemic toxicity. Further, doxorubicin delivery by temperature-sensitive liposomes can reliably cure local cancer in mouse models. Histological sections of treated tumors have detected red cell extravasation within tumors treated with temperature-sensitive doxorubicin and ultrasound. We hypothesize that the local release of drug into the tumor vasculature and resulting high drug concentration can alter vascular transport rate constants along with having direct tumoricidal effects...
April 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Jessica Lohrke, Anna-Lena Frisk, Thomas Frenzel, Laura Schöckel, Martin Rosenbruch, Gregor Jost, Diana Constanze Lenhard, Martin A Sieber, Volker Nischwitz, Astrid Küppers, Hubertus Pietsch
OBJECTIVES: Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution...
June 2017: Investigative Radiology
Annasofia Anemone, Lorena Consolino, Dario Livio Longo
OBJECTIVES: X-ray iodinated contrast media have been shown to generate contrast in MR images when used with the chemical exchange saturation transfer (CEST) approach. The aim of this study is to compare contrast enhancement (CE) capabilities and perfusion estimates between radiographic molecules and a Gd-based contrast agent in two tumour murine models with different vascularization patterns. METHODS: MRI-CEST and MRI-CE T1w images were acquired in murine TS/A and 4 T1 breast tumours upon sequential i...
May 2017: European Radiology
Hiroshi Nonoyama, Tohru Tanigawa, Rei Shibata, Hirokazu Tanaka, Nobuyuki Katahira, Yuichiro Horibe, Keiji Takemura, Kenta Murotani, Norio Ozeki, Hiromi Ueda
CONCLUSION: In the mouse, when a tympanic perforation is present, gadoteridol does not seem to cause ototoxicity. Gadodiamide may cause mild ototoxicity other than toxicity to the outer hair cells of the cochlea. OBJECTIVES: Endolymphatic hydrops have been visualized through intra-tympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. However, reports on the safety of GBCAs are limited...
November 2016: Acta Oto-laryngologica
Kojiro Suzuki, Shinji Naganawa, Naohiro Furuhashi, Masahiro Yamazaki, Hiroshi Ogawa, Hisashi Kawai
The purpose of this study was to investigate the feasibility of contrast-enhanced magnetic resonance (MR) pancreatography with intravenously administered gadolinium-based contrast material (GBCM) in healthy subjects. Eight healthy male subjects (age: 29-53 years old, median: 37 years old) were enrolled. Contrast-enhanced MR pancreatography was scanned with heavily T2-weighted three-dimensional fluid-attenuated inversion recovery (hT2W-3D-FLAIR) before and after intravenous GBCM administration. Two radiologists evaluated the images, referring to three-dimensional MR pancreatography by consensus...
May 2016: Nagoya Journal of Medical Science
Gregory J Wilson, Charles S Springer, Sarah Bastawrous, Jeffrey H Maki
PURPOSE: To characterize transverse relaxation in oxygenated whole blood with extracellular gadolinium-based contrast reagents by experiment and simulation. METHODS: Experimental measurements of transverse (1) H2 O relaxation from oxygenated whole human blood and plasma were made at 1.5 and 3.0 Tesla. Spin-echo refocused and free-induction decays are reported for blood and plasma samples containing four different contrast reagents (gadobenate, gadoteridol, gadofosveset, and gadobutrol), each present at concentrations ranging from 1 to 18 mM (i...
May 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Miriam Filippi, Marina Boido, Chiara Pasquino, Francesca Garello, Cinzia Boffa, Enzo Terreno
In this study, murine Mesenchymal Stem Cells (MSCs) labeled with the clinically approved MRI agent Gadoteridol through a procedure based on the hypo-osmotic shock were successfully tracked in vivo in a murine model of Spinal Cord Injury (SCI). With respect to iso-osmotic incubations, the hypo-osmotic labeling significantly increased the Gd(3+) cellular uptake, and enhanced both the longitudinal relaxivity (r1) of the intracellular Gadoteridol and the Signal to Noise Ratio (SNR) measured on cell pellets, without altering the biological and functional profile of cells...
August 2016: Experimental Neurology
Eric Lancelot
OBJECTIVES: Gadolinium-based contrast agents (GBCAs) have been used for years for magnetic resonance imaging examinations. Because of their rapid blood clearance, they were considered as very safe products until some of them were shown to induce nephrogenic systemic fibrosis in patients with renal failure and hypersignals on T1-weighted unenhanced brain scans of patients with normal renal function. To date, these adverse effects have been related almost exclusively to the use of low-stability linear agents, which are more prone to release free gadolinium...
November 2016: Investigative Radiology
Gregory J Wilson, Jeffrey H Maki
PURPOSE: To evaluate a contrast agent injection method that provides constant magnetic resonance imaging (MRI) signal intensity throughout a contrast-enhanced MR angiography acquisition. MATERIALS AND METHODS: A tailored injection profile (TIP) algorithm was developed that used the signal intensity profile from a test bolus as an impulse response function, and predicted the response to various multiphasic injection profiles. Antecubital vein injections were administered via a commercially available multiphasic power injector...
December 2016: Journal of Magnetic Resonance Imaging: JMRI
S Rizzitelli, P Giustetto, D Faletto, D Delli Castelli, S Aime, E Terreno
The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma...
May 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Nozomu Murata, Luis F Gonzalez-Cuyar, Kiyoko Murata, Corinne Fligner, Russell Dills, Daniel Hippe, Kenneth R Maravilla
OBJECTIVE: The purpose of this study was to determine whether gadolinium (Gd) is deposited in brain and bone tissues in patients receiving only non-Group 1 agents, either macrocyclic or linear protein interacting Gd-based contrast agents, with normal renal function. Group 1 agents are linear agents most associated with nephrogenic systemic fibrosis that the US Federal Drug Administration has defined as contraindicated in patients at risk for this disease. MATERIALS AND METHODS: This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant for retrospective review of records and also had signed autopsy consent authorizing use of decedent's tissue in research studies...
July 2016: Investigative Radiology
Yannan N Dou, Robert A Weersink, Warren D Foltz, Jinzi Zheng, Naz Chaudary, David A Jaffray, Christine Allen
Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors...
December 13, 2015: Journal of Visualized Experiments: JoVE
Andrew W Wong, Brett Z Fite, Yu Liu, Azadeh Kheirolomoom, Jai W Seo, Katherine D Watson, Lisa M Mahakian, Sarah M Tam, Hua Zhang, Josquin Foiret, Alexander D Borowsky, Katherine W Ferrara
Magnetic resonance-guided focused ultrasound (MRgFUS) facilitates noninvasive image-guided conformal thermal therapy of cancer. Yet in many scenarios, the sensitive tissues surrounding the tumor constrain the margins of ablation; therefore, augmentation of MRgFUS with chemotherapy may be required to destroy remaining tumor. Here, we used 64Cu-PET-CT, MRI, autoradiography, and fluorescence imaging to track the kinetics of long-circulating liposomes in immunocompetent mammary carcinoma-bearing FVB/n and BALB/c mice...
January 2016: Journal of Clinical Investigation
Jing Zou, Francis Talbot, Alessandra Tata, Leonardo Ermini, Kresimir Franjic, Manuela Ventura, Jinzi Zheng, Howard Ginsberg, Martin Post, Demian R Ifa, David Jaffray, R J Dwayne Miller, Arash Zarrine-Afsar
A picosecond infrared laser (PIRL) is capable of cutting through biological tissues in the absence of significant thermal damage. As such, PIRL is a standalone surgical scalpel with the added bonus of minimal postoperative scar tissue formation. In this work, a tandem of PIRL ablation with electrospray ionization (PIR-LAESI) mass spectrometry is demonstrated and characterized for tissue molecular imaging, with a limit of detection in the range of 100 nM for reserpine or better than 5 nM for verapamil in aqueous solution...
December 15, 2015: Analytical Chemistry
Gilles Soulez, Daniel C Bloomgarden, Neil M Rofsky, Martin P Smith, Hani H Abujudeh, Desiree E Morgan, Richard J Lichtenstein, Mark L Schiebler, Franz J Wippold, Craig Russo, Matthew J Kuhn, Kevin W Mennitt, Jeffrey H Maki, Alan Stolpen, Johnson Liou, Richard C Semelka, Miles A Kirchin, Ningyan Shen, Gianpaolo Pirovano, Alberto Spinazzi
OBJECTIVE: The purpose of this study was to determine the incidence of nephrogenic systemic fibrosis (NSF) in patients with chronic kidney disease (CKD) and moderate-to-severe impairment of kidney function who had not previously been exposed to gadolinium-based contrast agents (GBCAs) or referred to undergo contrast-enhanced MRI with gadobenate dimeglumine or gadoteridol. SUBJECTS AND METHODS: Two multicenter prospective cohort studies evaluated the incidence of unconfounded NSF in patients with stage 3 CKD (estimated glomerular filtration rate [eGFR] in cohort 1, 30-59 mL/min/1...
September 2015: AJR. American Journal of Roentgenology
M Filippi, D Patrucco, J Martinelli, M Botta, P Castro-Hartmann, L Tei, E Terreno
Dendrimersomes are nanosized vesicles constituted by amphiphilic Janus dendrimers (JDs), which have been recently proposed as innovative nanocarriers for biomedical applications. Recently, we have demonstrated that dendrimersomes self-assembled from (3,5)12G1-PE-BMPA-G2-(OH)8 dendrimers can be successfully loaded with hydrophilic and amphiphilic imaging contrast agents. Here, we present two newly synthesized low generation isomeric JDs: JDG0G1(3,5) and JDG0G1(3,4). Though less branched than the above-cited dendrimers, they retain the ability to form self-assembled, almost monodisperse vesicular nanoparticles...
August 14, 2015: Nanoscale
Alessandra Tata, Jinzi Zheng, Howard J Ginsberg, David A Jaffray, Demian R Ifa, Arash Zarrine-Afsar
Mapping intratumoral heterogeneity such as vasculature and margins is important during intraoperative applications. Desorption electrospray ionization mass spectrometry (DESI-MS) has demonstrated potential for intraoperative tumor imaging using validated MS profiles. The clinical translation of DESI-MS into a universal label-free imaging technique thus requires access to MS profiles characteristic to tumors and healthy tissues. Here, we developed contrast agent mass spectrometry imaging (CA-MSI) that utilizes a magnetic resonance imaging (MRI) contrast agent targeted to disease sites, as a label, to reveal tumor heterogeneity in the absence of known MS profiles...
August 4, 2015: Analytical Chemistry
Scott B Reeder, Matthew R Smith, Diego Hernando
PURPOSE: To develop and validate closed form mathematical expressions that predict the optimal contrast agent concentration for the maximum T1-weighted spoiled gradient echo (SGRE) signal. THEORY AND METHODS: Gadolinium and iron-based contrast agents can have significant transverse relaxivity that leads to signal dropout with increasing contrast agent concentration. A mathematical expression for the "optimal" contrast agent concentration where recovery of longitudinal magnetization is offset by increasing transverse signal decay was derived...
April 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Juan E Gutierrez, Martin Rosenberg, Jörg Seemann, Josy Breuer, Daniel Haverstock, Jacob Agris, Thomas Balzer, Nicoletta Anzalone
PURPOSE: Contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood-brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0...
2015: Magnetic Resonance Insights
Karen Y Oh, Victoria H J Roberts, Matthias C Schabel, Kevin L Grove, Mark Woods, Antonio E Frias
PURPOSE: To determine the extent to which gadolinium chelate is found in nonhuman primate fetal tissues and amniotic fluid at 19-45 hours after intravenous injection of a weight-appropriate maternal dose of the contrast agent gadoteridol. MATERIALS AND METHODS: Gravid Japanese macaques (n = 14) were maintained as approved by the institutional animal care and utilization committee. In the 3rd trimester of pregnancy, the macaques were injected with gadoteridol (0...
July 2015: Radiology
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