Abstract:
:Development and evaluation of new anticancer drugs are expedited when minimally invasive biomarkers of pharmacokinetic and pharmacodynamic behaviour are available. Gene-directed enzyme prodrug therapy (GDEPT) is a suicide gene therapy in which the anticancer drug is activated in the tumor by an exogenous enzyme previously targeted by a vector carrying the gene. GDEPT has been evaluated in various clinical trials using several enzyme/prodrug combinations. The key processes to be monitored in GDEPT are gene delivery and expression, as well as prodrug delivery and activation. {4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoyl}-L-glutamic acid, a prodrug for the GDEPT enzyme carboxypeptidase-G2 (CPG2; K(m) = 1.71 microM; k(cat) = 732 s(-1)), was measured with (19)F magnetic resonance spectroscopy (MRS). The 1 ppm chemical shift separation found between the signals of prodrug and activated drug (4-[bis(2-chloroethyl)amino]-3,5-difluorobenzoic acid) is sufficient for the detection of prodrug activation in vivo. However, these compounds hydrolyze rapidly, and protein binding broadens the MR signals. A new CPG2 substrate was designed with hydroxyethyl instead of chloroethyl groups (K(m) = 3.5 microM, k(cat) = 747 s(-1)). This substrate is nontoxic and stable in solution, has a narrow MRS resonance in the presence of bovine and foetal bovine albumin, and exhibits a 1.1 ppm change in chemical shift upon cleavage by CPG2. In cells transfected to express CPG2 in the cytoplasm (MDA MB 361 breast carcinoma cells and WiDr colon cancer cells), well-resolved (19)F MRS signals were observed from clinically relevant concentrations of the new substrate and its nontoxic product. The MRS conversion half-life (470 min) agreed with that measured by HPLC (500 min). This substrate is, therefore, suitable for evaluating gene delivery and expression prior to administration of the therapeutic agent.
journal_name
NMR Biomedjournal_title
NMR in biomedicineauthors
Mancini L,Davies L,Friedlos F,Falck-Miniotis M,Dzik-Jurasz AS,Springer CJ,Leach MO,Payne GSdoi
10.1002/nbm.1375subject
Has Abstractpub_date
2009-06-01 00:00:00pages
561-6issue
5eissn
0952-3480issn
1099-1492journal_volume
22pub_type
杂志文章abstract::This study investigated the association between the total choline (tCho) concentration and the clinical characteristics and biomarker status of breast cancer. Sixty-two patients with breast cancer, 1.5 cm or larger in size on MR images, were studied. The tCho concentration was correlated with the MRI features, contra...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1595
更新日期:2011-04-01 00:00:00
abstract::Proton NMR spectroscopy of biological fluids has produced interesting results lately. We used the technique to investigate the effects of cryopreservation on primary porcine hepatocytes as successful cryopreservation of primary porcine hepatocytes is of importance to the development of bioartificial liver support syst...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.765
更新日期:2002-05-01 00:00:00
abstract::The main aim of this study was to employ high-resolution MRI to investigate the spatiotemporal development of pathological features associated with contusive spinal cord injury (SCI) in mice. Experimental mice were subjected to either sham surgery or moderate contusive SCI. A 16.4-T small-animal MR system was employed...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.2829
更新日期:2013-02-01 00:00:00
abstract::It is generally accepted that tumour microcirculation, blood flow, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status--factors which are usually closely linked and which define the so-called metabolic microenvironment--can markedly influence the therapeutic response of malignant tumours to...
journal_title:NMR in biomedicine
pub_type: 杂志文章,评审
doi:10.1002/nbm.1940050505
更新日期:1992-09-01 00:00:00
abstract::Management of brain tumours in children would benefit from improved non-invasive diagnosis, characterisation and prognostic biomarkers. Metabolite profiles derived from in-vivo MRS have been shown to provide such information. Studies indicate that using optimum a priori information on metabolite contents in the constr...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1432
更新日期:2010-01-01 00:00:00
abstract::The intimal and medial linings of the pulmonary artery consist largely of vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), respectively. The migration of these cell types to a potential tissue-engineered pulmonary valve (TEPV) implant process is therefore of interest in understanding the val...
journal_title:NMR in biomedicine
pub_type: 杂志文章,评审
doi:10.1002/nbm.1642
更新日期:2012-03-01 00:00:00
abstract::The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level-dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is ano...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.2911
更新日期:2013-06-01 00:00:00
abstract::(31)P MRS provides a unique non-invasive window into myocardial energy homeostasis. Mouse models of cardiac disease are widely used in preclinical studies, but the application of (31)P MRS in the in vivo mouse heart has been limited. The small-sized, fast-beating mouse heart imposes challenges regarding localized sign...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3371
更新日期:2015-10-01 00:00:00
abstract::Chemical exchange saturation transfer (CEST) can offer information about protons associated with mobile proteins through the amide proton transfer (APT) effect, which has been shown to discriminate tumor from healthy tissue and, more recently, has been suggested as a prognosticator of response to therapy. Despite this...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.2947
更新日期:2013-10-01 00:00:00
abstract::Nuclear Overhauser enhancement (NOE) is a type of magnetization transfer using cross-relaxation. It originates from mobile macromolecules, which may have relevance to the evaluation of tumor features. We studied the value of NOE imaging at 7 and 3 T and suggest a utility for diagnosing human brain tumors. Two types of...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3735
更新日期:2017-09-01 00:00:00
abstract::The purpose of this study was to investigate the reliability of 3D isotropic MRI and quantitative multi-parametric MRI characterization on an orthotopic pancreatic head tumor model in rats. 3D isotropic T2 -weighted MRI was performed as a routine for tumor longitudinal follow-up and volume estimation. Common bile duct...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3676
更新日期:2017-02-01 00:00:00
abstract::Quantitative mapping of MR tissue parameters such as the spin-lattice relaxation time (T1 ), the spin-spin relaxation time (T2 ), and the spin-lattice relaxation in the rotating frame (T1ρ ), referred to as MR relaxometry in general, has demonstrated improved assessment in a wide range of clinical applications. Compar...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.4416
更新日期:2020-10-15 00:00:00
abstract::In vitro (1)H MRS of human bile has shown potential in the diagnosis of various hepatopancreatobiliary (HPB) diseases. Previously, in vivo (1)H MRS of human bile in gallbladder using a 1.5 T scanner demonstrated the possibility of quantification of choline-containing phospholipids (chol-PLs). However, other lipid comp...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3173
更新日期:2014-10-01 00:00:00
abstract::In recent years, quantitative nuclear magnetic resonance imaging and spectroscopy (NMRI and NMRS) have been used more systematically as outcome measures in natural history and clinical trial studies for Duchenne muscular dystrophy (DMD). Whereas most of these studies have emphasized the evaluation of the fat fraction ...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3839
更新日期:2018-01-01 00:00:00
abstract::Quantitative magnetisation transfer imaging (qMTI) is an extension of conventional MT techniques and allows the measurement of parameters that reflect tissue ultrastructure through the properties of macromolecule-bound protons; these include the bound proton fraction and the relaxation times of free and bound proton p...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1614
更新日期:2011-06-01 00:00:00
abstract::In recent years considerable effort has been devoted to applying pattern recognition techniques to the complex task of data analysis in magnetic resonance spectroscopy. It may be argued that such techniques will facilitate putting MRS technology to practical clinical use. This paper reviews approaches of pattern recog...
journal_title:NMR in biomedicine
pub_type: 杂志文章,评审
doi:10.1002/(sici)1099-1492(199705)10:3<99::aid-nbm461
更新日期:1997-05-01 00:00:00
abstract::The aim of this study was to measure choline/creatine (Ch/Cr) levels through (1)H-MRS and apparent diffusion coefficient (ADC) values through diffusion-weighted MRI, and to correlate these values with the prognostic parameters of head and neck squamous cell carcinoma (HNSCC). The institutional review board approved th...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3472
更新日期:2016-04-01 00:00:00
abstract::Quantitative susceptibility mapping (QSM) is a recently developed MRI technique that provides a quantitative measure of tissue magnetic susceptibility. To compute tissue magnetic susceptibilities based on gradient echoes, QSM requires reliable unwrapping of the measured phase images and removal of contributions caused...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3056
更新日期:2014-02-01 00:00:00
abstract::The scyllo-inositol and myo-inositol concentrations of 24 normal human subjects were measured in vivo using 1H magnetic resonance spectroscopy at 4 T. Single-voxel short-echo (TE = 15 ms) metabolite spectra were collected from the white matter region of the corona radiata. Test-retest studies performed on 10 normal su...
journal_title:NMR in biomedicine
pub_type: 临床试验,杂志文章
doi:10.1002/nbm.927
更新日期:2005-02-01 00:00:00
abstract::The ability to assess the perfusion territories of major cerebral arteries can be a valuable asset to the diagnosis of a number of cerebrovascular diseases. Recently, several arterial spin labeling (ASL) techniques have been proposed for determining the cerebral perfusion territories of individual arteries by three di...
journal_title:NMR in biomedicine
pub_type: 杂志文章,评审
doi:10.1002/nbm.1177
更新日期:2007-11-01 00:00:00
abstract::The myeloproliferative leukemic virus (MPLV) induces within 2-3 weeks a massive infiltration of the adult mouse liver by hematopoietic leukemic cells. Since the metabolism of the infiltrated organ might be correlated with an interaction of two cell populations, it was decided to study the isolated hematopoietic cells ...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1940020106
更新日期:1989-06-01 00:00:00
abstract::Traditional methods of measuring magnetization in magnetic fluid samples, such as vibrating sample magnetometry (VSM), are typically limited to maximum field strengths of about 1 T. This work demonstrates the ability of MRI to measure the magnetization associated with two commercial MRI contrast agents at 3 T by compa...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1412
更新日期:2009-10-01 00:00:00
abstract::The aim of this study was to investigate proton changes of the parotid gland after gustatory stimulation by semi-quantitative parameters and an empirical mathematical model (EMM) using high-temporal-resolution, double-echo, echo-planar imaging (EPI). Approved by a local institutional review board, this study examined ...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3885
更新日期:2018-03-01 00:00:00
abstract::The dependence of apparent diffusion coefficients (ADCs) of molecules in biological tissues on an acquisition-specific timescale is a powerful mechanism for studying tissue microstructure. Unlike water, metabolites are confined mainly to intracellular compartments, thus providing higher specificity to tissue microstru...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3085
更新日期:2014-05-01 00:00:00
abstract::Studies of cholesteryl ester transfer protein (CETP) function in lipoprotein mixtures pose many difficulties by conventional biochemical methods. For instance, studies on the effects of CETP on the composition of apolipoprotein B containing lipoproteins (very low and low density lipoproteins) in lipoprotein mixtures a...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/(sici)1099-1492(199710)10:7<303::aid-nbm48
更新日期:1997-10-01 00:00:00
abstract::The purpose of this study was to investigate the effect of gadolinium (III) diethyltriaminepenta-acetic acid (Gd-DTPA) mixed with a fixative on the image contrast between the white and gray matter of the perfusion-fixed mouse brain. A series of microscopic MRI (microMRI) studies using different concentrations of Gd-DT...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1324
更新日期:2009-04-01 00:00:00
abstract::Perfusion is an important biomarker of tissue function and has been associated with tumor pathophysiology such as angiogenesis and hypoxia. Arterial spin labeling (ASL) MRI allows noninvasive and quantitative imaging of perfusion; however, the application in mouse xenograft tumor models has been challenging due to the...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.3330
更新日期:2015-08-01 00:00:00
abstract::This review highlights various magnetic resonance image (MRI) segmentation algorithms that employ pattern recognition. The procedures are grouped into two categories: low- to intermediate-level, and high-level image processing. The former consists of grey level histogram analysis, texture definition, edge identificati...
journal_title:NMR in biomedicine
pub_type: 杂志文章,评审
doi:10.1002/(sici)1099-1492(199806/08)11:4/5<157::aid-
更新日期:1998-06-01 00:00:00
abstract::Following the impetus of early clinical and experimental investigations, in vivo and in vitro MRS studies of tumours pointed in the eighties to the possible significance of signals arising from phospholipid (PL) precursors and catabolites as novel biochemical indicators of in vivo tumour progression and response to th...
journal_title:NMR in biomedicine
pub_type: 杂志文章,评审
doi:10.1002/(sici)1099-1492(199911)12:7<413::aid-nbm58
更新日期:1999-11-01 00:00:00
abstract::We have developed a reliable, reproducible model of hypoxia in the gerbil. 1H and 31P NMR spectroscopy demonstrates that cerebral energy metabolism is very resistant to hypoxia. Cerebral blood flow (measured by hydrogen clearance) began to increase when the arterial oxygen tension (paO2) was reduced to 40-50 mm Hg, an...
journal_title:NMR in biomedicine
pub_type: 杂志文章
doi:10.1002/nbm.1940050109
更新日期:1992-01-01 00:00:00