Matrix metalloproteinase-12 (MMP-12) is highly upregulated in several inflammatory diseases, including abdominal aortic aneurysm (AAA). Here we report four novel Tc-labeled radiotracers derived from a highly selective competitive MMP-12 inhibitor. These tracers in their Tc version were assessed in vitro on a set of human metalloproteases and displayed high affinity and selectivity toward MMP-12.
View Article and Find Full Text PDFColon interposition is a surgical procedure used for maintenance of luminal conduit after esophagectomy. Although epithelial neoplasia, such as adenoma and adenocarcinoma, may develop in the interposed colon, there are only few case reports on the condition. Due to the rarity of this condition, there is no definite consensus on recommending screening endoscopy for the early detection of neoplasia in the interposed colons.
View Article and Find Full Text PDFMyeloperoxidase (MPO) is a critical proinflammatory enzyme implicated in cardiovascular, neurological, and rheumatological diseases. Emerging therapies targeting inflammation have raised interest in tracking MPO activity in patients. We describe F-MAPP, an activatable MPO activity radioprobe for positron emission tomography (PET) imaging.
View Article and Find Full Text PDFTumor-associated macrophages (TAMs) are widely implicated in cancer progression, and TAM levels can influence drug responses, particularly to immunotherapy and nanomedicines. However, it has been difficult to quantify total TAM numbers and their dynamic spatiotemporal distribution in a non-invasive and translationally relevant manner. Here, we address this need by developing a pharmacokinetically optimized, Cu-labeled polyglucose nanoparticle (Macrin) for quantitative positron emission tomography (PET) imaging of macrophages in tumors.
View Article and Find Full Text PDFMatrix metalloproteinases (MMPs) are involved in tissue remodeling. Accordingly, MMP inhibitors and related radiolabeled analogs are important tools for MMP-targeted imaging and therapy in a number of diseases. Herein, we report design, synthesis, and evaluation of a new Arginine-containing macrocyclic hydroxamate analog, RYM, its hydrazinonicotinamide conjugate, RYM1 and Tc-labeled analog Tc-RYM1 for molecular imaging.
View Article and Find Full Text PDFRationale: Inflammatory stress induced by exposure to bacterial lipopolysaccharide causes hematopoietic stem cell expansion in the bone marrow niche, generating a cellular immune response. As an integral component of the hematopoietic stem cell niche, the bone marrow vasculature regulates the production and release of blood leukocytes, which protect the host against infection but also fuel inflammatory diseases.
Objective: We aimed to develop imaging tools to explore vascular changes in the bone marrow niche during acute inflammation.
Noninvasive detection of both early pancreatic neoplasia and metastases could enhance strategies to improve patient survival in this disease that is notorious for an extremely poor prognosis. There are almost no identifiable targets for non-invasive diagnosis by positron emission tomography (PET) for patients with pancreatic ductal adenocarcinoma (PDAC). Over-expression of the receptor for advanced glycation end products (RAGE) is found on the cell surface of both pre-neoplastic lesions and invasive PDAC.
View Article and Find Full Text PDFIn barley, breeding using good genetic characteristics can improve the quality or quantity of crop characters from one generation to the next generation. The development of effective molecular markers in barley is crucial for understanding and analyzing the diversity of useful alleles. In this study, we conducted genetic relationship analysis using expressed sequence tag-simple sequence repeat (EST-SSR) markers for barley identification and assessment of barley cultivar similarity.
View Article and Find Full Text PDFFluorescence imaging is a powerful technique with diverse applications in intraoperative settings. Visualization of three dimensional (3D) structures and depth assessment of lesions, however, are oftentimes limited in planar fluorescence imaging systems. In this study, a novel Fluorescence Imaging Topography Scanning (FITS) system has been developed, which offers color reflectance imaging, fluorescence imaging and surface topography scanning capabilities.
View Article and Find Full Text PDFMatrix metalloproteinases (MMPs) play a key role in abdominal aortic aneurysm (AAA) development. Accordingly, MMP-targeted imaging provides important information regarding vessel wall biology in the course of aneurysm development. Given the small size of the vessel wall and its proximity with blood, molecular imaging of aneurysm optimally requires highly sensitive tracers with rapid blood clearance.
View Article and Find Full Text PDFTissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients.
View Article and Find Full Text PDFMatrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm.
View Article and Find Full Text PDFCalcific aortic valve disease (CAVD) is the most common cause of aortic stenosis. Currently, there is no non-invasive medical therapy for CAVD. Matrix metalloproteinases (MMPs) are upregulated in CAVD and play a role in its pathogenesis.
View Article and Find Full Text PDFUnlabelled: Imaging techniques for detection of molecular and cellular processes that precede or accompany lung diseases are needed. Matrix metalloproteinases (MMPs) play key roles in the development of pulmonary pathology. The objective of this study was to investigate the feasibility of in vivo MMP-targeted molecular imaging for detection of lung inflammation and remodeling.
View Article and Find Full Text PDFObjectives This study evaluated the objective response to and toxicity of trans-arterial chemo-embolisation (TACE) followed by radiotherapy and hyperthermia (CERT) in hepatocellular carcinoma patients with portal vein tumour thrombosis. Methods The study design was a single-centre prospective phase II trial. Patients were first treated with TACE, with the first hyperthermia session 1 week later.
View Article and Find Full Text PDFVEGFR1 is a receptor tyrosine kinase that has been implicated in cancer pathogenesis. It is upregulated in angiogenic endothelial cells and expressed on human tumor cells as well. VEGFR1 positive hematopoietic progenitor cells home to sites of distant metastases prior to the arrival of the tumor cells thus establishing a pre-metastatic niche.
View Article and Find Full Text PDFHealthc Inform Res
July 2015
[This corrects the article on p. 118 in vol. 21, PMID: 25995964.
View Article and Find Full Text PDFHealthc Inform Res
April 2015
Objectives: The widespread adoption of health information technology (IT) will help contain health care costs by decreasing inefficiencies in healthcare delivery. Theoretically, health IT could lower hospitals' malpractice insurance premiums (MIPs) and improve the quality of care by reducing the number and size of malpractice. This study examines the relationship between health IT investment and MIP using California hospital data from 2006 to 2007.
View Article and Find Full Text PDFPurpose: The aim of this study is to investigate the use of mixture of BaSO4 and biodegradable polymer as an injectable nonmetallic fiducial marker to reduce artifacts in x-ray images, decrease the absorbed dose distortion in proton therapy, and replace permanent metal markers.
Methods: Two samples were made with 90 wt. % polymer phosphate buffer saline (PBS) and 10 wt.
In response to inflammatory stimuli, microvascular endothelial cells become activated, initiating the capture and exit of neutrophils from the blood vessel and into the extravascular extracellular matrix (ECM). In the extravascular space, neutrophils bind to ECM proteins, regulating cellular functions via signaling through adhesion molecules known as integrins. The αβ integrin is an important mediator of neutrophil adhesion to ECM proteins containing the Arg-Gly-Asp (RGD) peptide sequence, including fibrinogen and fibronectin.
View Article and Find Full Text PDFIn this study, an anti-hapten antibody (single chain Fv, scFv) against a hapten probe was developed as a unique reporter system for molecular imaging or therapy. The hapten peptide (histamine-succinyl-GSYK, Him) was synthesized for phage displayed scFv affinity selection and for conjugation with cypate (Cy-Him) for in vivo near-infrared (NIR) optical imaging. Hapten-specific scFvs were affinity selected from the human single fold phage display scFv libraries (Tomlinson I + J) with high specificity and affinity.
View Article and Find Full Text PDFIntervertebral disc degeneration (IDD) is closely associated with low back pain. Typically nonsurgical treatment of IDD is the most effective when detected early. As such, establishing reliable imaging methods for the early diagnosis of disc degeneration is critical.
View Article and Find Full Text PDFAm J Nucl Med Mol Imaging
March 2013
Neurofibrillary tangles (NFTs) have long been recognized as one of the pathological hallmarks in Alzheimer's disease (AD). Recent studies, however, showed that soluble aggregated Tau species, especially hyperphosphorylated Tau oligomers, which are formed at early stage of AD prior to the formation of NFT, disrupted neural system integration. Unfortunately, little is known about Tau aggregates, and few Tau targeted imaging probe has been reported.
View Article and Find Full Text PDFDrug targeting to tumors with limited toxicity and enhanced efficacy of drug is one of the important goals for cancer treatment pharmaceutics. Monocytes/macrophages are able to migrate to tumor sites across the blood barriers by acting as Trojan horses carrying drug cargoes. Taking this advantage, we have intended to develop an efficient administration system using a biologically active carrier of mouse peritoneal macrophage bearing liposomal doxorubicin (macrophage-LP-Dox).
View Article and Find Full Text PDFCyclodextrin (CD) is a well known drug carrier and excipient for enhancing aqueous solubility. CDs themselves are anticipated to have low membrane permeability because of relatively high hydrophilicity and molecular weight. CD derivatization with 17-beta estradiol (E(2)) was explored extensively using a number of different click chemistries and the cell membrane permeability of synthetic CD-E(2) conjugate was explored by cell reporter assays and confocal fluorescence microscopy.
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