A5087360640- Lanthanide and Transition Metal Complexes
- Advanced MRI Techniques and Applications
- Pancreatic and Hepatic Oncology Research
- Trace Elements in Health
- Radiomics and Machine Learning in Medical Imaging
- Liver Disease Diagnosis and Treatment
- MRI in cancer diagnosis
- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Drug Transport and Resistance Mechanisms
- Nanoparticle-Based Drug Delivery
- Molecular Sensors and Ion Detection
- Gastrointestinal Tumor Research and Treatment
- Sarcoma Diagnosis and Treatment
- Magnetism in coordination complexes
- Heavy Metal Exposure and Toxicity
- Electron Spin Resonance Studies
- Cancer, Hypoxia, and Metabolism
- Clinical Nutrition and Gastroenterology
- Liver physiology and pathology
- Phagocytosis and Immune Regulation
- Healthcare Systems and Technology
- Patient Satisfaction in Healthcare
- Primary Care and Health Outcomes
- Patient-Provider Communication in Healthcare
Massachusetts General Hospital
2019-2024
Harvard University
2019-2024
Athinoula A. Martinos Center for Biomedical Imaging
2019-2024
The University of Texas Southwestern Medical Center
2015-2023
Advanced Imaging Research (United States)
2015-2023
Santa Rosa Junior College
2018
Corporació Sanitària Parc Taulí
2015
Arizona State University
2010
Duke Medical Center
2005
We introduce a redox-active iron complex, Fe-PyC3A, as biochemically responsive MRI contrast agent. Switching between Fe3+-PyC3A and Fe2+-PyC3A yields full order of magnitude relaxivity change that is field-independent 1.4 11.7 T. The oxidation to by hydrogen peroxide very rapid, we capitalized on this behavior for the molecular imaging acute inflammation, which characterized elevated levels reactive oxygen species. Injection generates strong, selective enhancement inflamed pancreatic tissue...
Given the known water exchange rate limitations of a previously reported Zn(II)-sensitive MRI contrast agent, GdDOTA-diBPEN, new structural targets were rationally designed to increase improve detection sensitivity. These sensors exhibit fine-tuned properties and, depending on individual structure, demonstrate significantly improved longitudinal relaxivities (r1). Two in particular optimized parameters therefore, show exceptionally high about 50 mM(-1) s(-1) upon binding Zn(II) and human...
It has been demonstrated that divalent zinc ions packaged with insulin in β-cell granules can be detected by MRI during glucose-stimulated secretion using a gadolinium-based Zn2+-sensitive agent. This study was designed to evaluate whether simpler agent design having single Zn2+-sensing moieties but variable Zn2+ binding affinities might also detect from the pancreas. Using an implanted MR-compatible window hold pancreas fixed position for imaging, we now demonstrate focally intense "hot...
Objectives The goals of this study were to compare the efficacy new manganese-based magnetic resonance imaging (MRI) contrast agent Mn-PyC3A commercial gadolinium-based agents Gd-DOTA and Gd-EOB-DTPA detect tumors in murine models breast cancer metastatic liver disease, respectively, quantify fractional excretion elimination rats. Methods T1-weighted contrast-enhanced MRI with 0.1 mmol/kg was compared a mouse model (n = 8) 0.025 metastasis 6). excretion, 1-day biodistribution, 7-day...
Abstract The recent past has seen impressive progress in the treatment of various malignancies using immunotherapy. One most promising approaches involves immune checkpoint inhibitors. However, clinical results with these agents have demonstrated variability response. Pancreatic cancer, particular, proven resistant to initial immunotherapy approaches. Here, we describe an alternative strategy that relies on combining gemcitabine and a novel programmed death-ligand 1 (PD-L1) inhibitor, termed...
The design, synthesis, and properties of a new gadolinium-based copper-responsive magnetic resonance imaging (MRI) contrast agent is presented. sensor (GdL1) has high selectivity for copper ions exhibits 43% increase in r1 relaxivity (20 MHz) upon binding to 1 equiv Cu2+ aqueous buffer. Interestingly, the presence physiological levels human serum albumin (HSA), amplified further up 270%. Additional spectroscopic X-ray absorption spectroscopy (XAS) studies show that coordinated by two...
Abstract Purpose: To evaluate the prognostic value of posttreatment fibrosis in human PDAC patients, and to compare a type I collagen targeted MRI probe, CM-101, standard contrast agent, Gd-DOTA, for their abilities identify FOLFIRINOX-induced murine model PDAC. Experimental Design: Ninety-three chemoradiation-treated samples were stained outcomes evaluated. For imaging, C57BL/6 FVB mice orthotopically implanted with cells FOLFIRINOX was administered. Mice imaged Gd-DOTA CM-101. Results: In...
During liver fibrosis, tissue repair mechanisms replace necrotic with highly stabilized extracellular matrix proteins. Extracellular stabilization influences the speed of recovery. Here, we studied expression and function peroxidasin (PXDN), a peroxidase that uses hydrogen peroxide to cross-link collagen IV during fibrosis progression regression.Mouse models cirrhosis patients were analyzed for PXDN in serum. Pxdn-/- Pxdn+/+ mice either treated carbon tetrachloride 6 weeks generate...
Gadolinium-based contrast agents (GBCAs) are used to provide diagnostic information in clinical magnetic resonance (MR) examinations. Gadolinium (Gd) has been detected the brain, bone and skin of patients, months years following GBCA administration, raising concerns about long term toxicity. Despite increased scrutiny, concentration, chemical form fate retained gadolinium species remain unknown. Importantly, whole body biodistribution organ clearance GBCAs is poorly understood humans. lacks...
Background Liver biopsy is the reference standard to diagnose nonalcoholic steatohepatitis (NASH) but invasive with potential complications. Purpose To evaluate molecular MRI type 1 collagen–specific probe EP-3533 and allysine-targeted fibrogenesis Gd-Hyd, MR elastography, native T1 characterize fibrosis assess treatment response in a rat model of NASH. Materials Methods was performed prospectively (June–November 2018) six groups male Wistar rats (a) age- (b) weight-matched animals received...
A Mn(II)-based zinc-sensitive MRI contrast agent, MnPyC3A-BPEN, was prepared, characterized, and applied in imaging experiments to detect glucose-stimulated zinc secretion (GSZS) from the mouse pancreas prostate
Abstract Magnetoferritin nanoparticles have been developed as high‐relaxivity, functional contrast agents for MRI. Several previous techniques relied on unloading native ferritin and re‐incorporation of iron into the core, often resulting in a polydisperse sample. Here, simplified technique is using commercially available horse spleen apoferritin to create monodisperse magnetoferritin. Iron oxide atoms were incorporated protein core via step‐wise Fe(II)Chloride addition solution under low O...
The EuII complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tetra(glycinate) has a higher reduction potential than most chelates reported to date. reduced form acts as an efficient water proton T1 relaxation reagent, while the EuIII water-based chemical exchange saturation transfer (CEST) agent. extremely fast rate. Oxidation corresponding yields well-defined signal from paraCEST time course oxidation was studied in vitro and vivo by T1-weighted CEST imaging.
Complexes of Fe3+ engage in rich aqueous solution speciation chemistry which discrete molecules can react with solvent water to form multinuclear μ-oxo and μ-hydroxide bridged species. Here we demonstrate how pH- concentration-dependent equilibration between monomeric μ-oxo-bridged dimeric complexes be controlled through judicious ligand design. We purposed this develop a first-in-class Fe3+-based MR imaging probe, Fe-PyCy2AI, that undergoes relaxivity change via pH-mediated control monomer...
Abstract Zinc has long been the focus of many biological investigations because its essential role in biology including a catalytic enzymes, structural zinc finger proteins, and physiological secretory cell processes. Divalent is known to be highly abundant healthy prostate tissues lower cancer (PCa). Given need for newer diagnostic methods detection cancer, zinc‐responsive probes various types have considered as imaging tools detecting tissue levels zinc. Among them, recent MRI show great...
Prostatic zinc content is a known biomarker for discriminating normal healthy tissue from benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Given that not readily measured without biopsy, we have been exploring noninvasive imaging methods to detect these diagnostic differences using zinc-responsive MRI contrast agent. During studies in mice, observed bolus of glucose stimulates secretion the fasted mice. This discovery allowed use Gd-based sensor differential regions versus...
In this work, we describe a novel DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) based ligand with chromophoric tropone coordinating sidearm (1). Ln3+ complexes of 1 have one inner sphere water molecule. The r1 relaxivity Gd1 is similar to that the commercial Gd-based MRI agents. neutral O-donor atom moiety slows down exchange rate by factor 3 compared GdDOTA. addition, Nd1 and Yb1 exhibit significant NIR emission in aqueous solutions indicating unit an efficient sensitizer...
Non-invasive beta cell function measurements may provide valuable information for improving diabetes diagnostics and disease management as the integrity of pancreatic cells have been found to be compromised in Type-1 Type-2 diabetes. Currently, available assays either lack functional or spatial identification cells. In this work, we introduce a method assess non-human primate pancreas non-invasively with MRI using Gd-based zinc(II) sensor contrast agent, Gd-CP027. Additionally, highlight...
Objectives In the United States, prostate cancer (PCa) is most common in men. Multi-parametric magnetic resonance imaging (MRI) increasingly being relied upon for diagnosis and characterization of PCa, but differentiating malignancy from benign prostatic hyperplasia (BPH) transition zone using MRI can be challenging. The characteristically high levels zinc human tissue a close relationship between malignant proliferation homeostatic dysregulation create opportunities to visualize PCa with...
Abstract The Eu II complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) tetra(glycinate) has a higher reduction potential than most chelates reported to date. reduced form acts as an efficient water proton T 1 relaxation reagent, while the III water‐based chemical exchange saturation transfer (CEST) agent. extremely fast rate. Oxidation corresponding yields well‐defined signal from paraCEST time course oxidation was studied in vitro and vivo by ‐weighted CEST imaging.
Many liver diseases are driven by inflammation, but imaging to non-invasively diagnose and quantify inflammation has been underdeveloped. The inflammatory microenvironment is aberrantly oxidising owing in part reactive oxygen species generated myeloid leucocytes. We hypothesised that magnetic resonance using the oxidatively activated probe Fe-PyC3A will provide a non-invasive biomarker of inflammation.