A5085433487- Nanoparticle-Based Drug Delivery
- Cerebrospinal fluid and hydrocephalus
- Advanced MRI Techniques and Applications
- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Lanthanide and Transition Metal Complexes
- Glioma Diagnosis and Treatment
- Polymer Surface Interaction Studies
- Traumatic Brain Injury and Neurovascular Disturbances
- Characterization and Applications of Magnetic Nanoparticles
- Protein purification and stability
- Chemical Reactions and Isotopes
- MRI in cancer diagnosis
- Advanced Neuroimaging Techniques and Applications
- Virus-based gene therapy research
- Biochemical and Molecular Research
- Neuroscience and Neuropharmacology Research
- Amino Acid Enzymes and Metabolism
- Fetal and Pediatric Neurological Disorders
- Lysosomal Storage Disorders Research
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Planarian Biology and Electrostimulation
- Inhalation and Respiratory Drug Delivery
- Cannabis and Cannabinoid Research
Harvard University
2007-2021
Massachusetts General Hospital
2011-2021
Shriners Hospitals for Children - Boston
2011-2021
Harvard University Press
1993-2015
Gordon Center for Medical Imaging
2015
Shriners Hospitals for Children - Erie
2012
Mersana Therapeutics (United States)
2007
Harvard–MIT Division of Health Sciences and Technology
1993
Institute of Experimental Cardiology
1985-1988
Russian Academy of Sciences
1985
Abstract We have previously described a novel monocrystalline iron oxide nanocompound (MION), stable colloid that enables target specific MR imaging. In this study, the physicochemical properties of MION are reported using variety analytical techniques. High resolution electron microscopy indicates consists hexagonal shaped electron‐dense cores 4.6 ± 1.2 nm in diameter. This core has an inverse spinel crystal structure which was confirmed by x‐ray powder diffraction. Chemical analysis showed...
The authors developed and evaluated a polymer as contrast agent for magnetic resonance (MR) angiography. consists of monomethoxy ether poly(ethylene glycol) covalently attached to poly(L-lysine) (PL), with PL serving the carrier gadolinium diethylenetriaminepentaacetic acid (DTPA). Immunogenicity toxicity studies were performed in mice, biokinetic metabolic rats. Dose response three-dimensional time-of-flight sequence eight No permanent immune was elicited against Gd-DTPA or molecule,...
A major challenge for the treatment of many central nervous system (CNS) disorders is lack convenient and effective methods delivering biological agents to brain. Mucopolysaccharidosis II (Hunter syndrome) a rare inherited lysosomal storage disorder resulting from deficiency iduronate-2-sulfatase (I2S). I2S large, highly glycosylated enzyme. Intravenous administration not likely be an therapy disease-related neurological outcomes that require enzyme access brain cells, in particular neurons...
The hypothesis is suggested describing the molecular mechanism of protective action poly(ethylene glycol) on liposomes in vivo basis polymer properties solvent. layer liposome surface considered as a "cloud" possible conformations macromolecules. If water-soluble and has flexible main chain, density this cloud high enough to prevent interaction opsonins with liposome. At same time, certain optimal concentration can be found, when more loose areas polymeric "clouds" used for immobilization...
PURPOSE: To investigate the utility of a monocrystalline iron oxide nanoparticle (MION) as contrast agent in magnetic resonance (MR) imaging lymph nodes. MATERIALS AND METHODS: Pharmacokinetic data were obtained rats after intravenous, subcutaneous, and intraarterial injection indium-111-MION-46. MR was performed to determine optimal dosages pulse sequences rats. Models node metastasis rabbits hyperplasia used demonstrate efficacy MION differentiation malignant benign adenopathies. RESULTS:...
Abstract Degenerative skin diseases affect one third of individuals over the age sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since many tissue components including cells extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique with pulsed electric fields. The fields destroy while simultaneously completely preserving matrix architecture releasing multiple...
Abstract 29 Si nuclear magnetic resonance (NMR) spectroscopy is applied to study the degradation of polysiloxanes (silicones) in vivo. Our results with animal models show that silicone migrates from implant liver ( at −20 ppm) and new silicon containing compounds form after silicones are introduced into rats. The resonances chemical shift range −40 −85 ppm related hydrolyzed silicone, those −90 −115 indicative presence silica (SiO 2 ), peaks observed −120 −150 high coordinated complexes....
Abstract A model system of a paramagnetic lymphotropic MR contrast agent (Gd‐DTPA labeled polyglucose associated macrocomplex, PGM) for T 1 ‐weighted imaging lymph nodes in rats and rabbits was evaluated. Pharmacokinetic (tissue accumulation) data (optimal dose timing parameters) were obtained normal ( n = 88) after subcutaneous (SC) injection paramagnetic, radiolabeled [111In]Gd‐DTPA‐PGM. rabbit node metastases 8) ultimately used to demonstrate the potential with Gd‐DTPA‐PGM nodal tumor...
The increasing number of studies demonstrates the high potency intrathecal (IT) route for delivery biopharmaceuticals to central nervous system (CNS). Our earlier data exhibited that both infused volume and infusion rate can regulate initial disposition administered solute within cerebrospinal fluid (CSF). This is one key factors in defining subsequent transport its intended target. On other hand, fast additions large volumes liquid CSF inevitably raise pressure [a.k.a. intracranial (ICP)],...
With the growing number of biotechnology products and drug delivery systems entering preclinical clinical studies, pharmacological imaging studies with PET play an increasingly significant role. Such often require investigation slow complex pharmacokinetics (PK). This suggests labeling candidate radionuclides that have long physical half-lives. Among currently available positron emitters, 124I has longest half-life (4.2 days). This, combined well-investigated behavior iodine in vivo, makes...
Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, evaluate irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound 6 (identified from a therapeutic agent) was advanced 18F-labeling via novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability excellent...
PURPOSE: To determine the pharmacokinetic and magnetic resonance (MR) imaging properties of diethylenetriaminepentaacetic acid (DTPA) conjugated with a polyglucose-associated macrocomplex (PGM), which accumulates in lymph nodes. MATERIALS AND METHODS: In 124 normal 20 tumor-bearing rats, Gd-DTPA PGM was administered intravenously doses 2, 10, mumol gadolinium per kilogram tissue. RESULTS: Mean blood half-life 2 hours. Maximum accumulation peripheral (33.0% injected dose [ID]/g +/- 16.2...
A water soluble macromolecular conjugate of camptothecin (CPT) with a new, dual phase hydrolytic drug release mechanism was prepared on the basis 60 kDa biodegradable hydrophilic "stealth" polyacetal, poly(1-hydroxymethylethylene hydroxy-methyl formal). Succinamido-glycinate used as prodrug releasing group. model preparation 7.5% CPT content w/w soluble. The lipophilic prodrug, camptothecin-(O20)-succinimidoglycinate, released from t(1/2) = 2.2 +/- 0.1 h in rodent plasma. blood clearance...
Despite recent advances in our understanding the pathophysiology of trauma, basis predisposition trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and model was used identify host genetic components that contribute hyper-susceptibility follows severe trauma. We show P. compromises skeletal muscle gene (SMG) expression at site promote infection. demonstrate activation SMG structural is under control cJun-N-terminal Kinase (JNK) Kinase,...
Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation ECM accumulation during chronic liver disease. Our group recently developed an 18F-labeled inhibitor ([18F]MAGL-4-11) for PET imaging demonstrated...