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AJNR. American Journal of Neuroradiology 1996To describe the MR characteristics that can distinguish idiopathic transverse myelitis from other intramedullary lesions.
PURPOSE
To describe the MR characteristics that can distinguish idiopathic transverse myelitis from other intramedullary lesions.
METHODS
A total of 32 initial and follow-up MR studies in 17 patients with clinically proved transverse myelitis were reviewed retrospectively. The location, size, pattern, and segmental length of areas of hyperintensity were estimated on T2-weighted axial and sagittal images. In 15 of the patients, whose neurologic abnormalities were limited to the spinal cord, the location and pattern of intramedullary contrast enhancement were evaluated on sagittal and axial T1-weighted images. Follow-up MR studies were available for 10 patients. The statistical significance of cord enhancement between the groups with and without cord expansion was calculated.
RESULTS
Common MR findings of idiopathic transverse myelitis included a centrally located hyperintensity occupying more than two thirds of the cross-sectional area of the cord (88%); a length of 3 to 4 vertebral segments (53%), with variable presence of cord expansion (47%); a small central area of intensity, isointense with normal cord, in the core of hyperintensity (47%); focal, peripheral cord enhancement (53%), particularly in patients with cord expansion; and a slow regression of T2 hyperintensity with an enhancing nodule. Although no linear correspondence was observed between MR findings and neurologic signs and symptoms, all but 4 patients improved clinically as MR findings improved or remained stable.
CONCLUSIONS
MR findings are helpful in detecting transverse myelitis and in differentiating this entity from multiple sclerosis and cord tumors, but clinical assessment and observation of MR changes over time are essential in making the diagnosis.
Topics: Adult; Contrast Media; Diagnosis, Differential; Drug Combinations; Female; Follow-Up Studies; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Male; Meglumine; Middle Aged; Myelitis, Transverse; Neurologic Examination; Organometallic Compounds; Pentetic Acid; Retrospective Studies; Spinal Cord; Spinal Cord Compression
PubMed: 8791931
DOI: No ID Found -
Regulatory Toxicology and Pharmacology... Feb 2024Aminocarboxylic acid (ethylenediamine-based) chelating agents such as DTPA are widely used in a variety of products and processes. Recently, DTPA was classified in the... (Review)
Review
Aminocarboxylic acid (ethylenediamine-based) chelating agents such as DTPA are widely used in a variety of products and processes. Recently, DTPA was classified in the European Union as a developmental toxicant CLP Category 1B. However, according to the CLP regulation (CLP, 2008) classification as a developmental toxicant requires a chemical to possess an intrinsic, specific property to do so. This paper provides overwhelming evidence that shows the developmental toxicity only seen at a sustained high dose of 1000 mg DTPA/kg bw/day in rats during pregnancy is mediated by zinc depletion which leads to non-specific secondary effects associated with zinc deficiency. Therefore, based on the CLP regulation itself, viz. the lack of a specific, intrinsic property, supported by significant differences in zinc kinetics and physiology between pregnant rats and pregnant women, DTPA should not be classified as a developmental toxicant. Moreover, classification for developmental toxicity resulting from zinc deficiency, and only observed at high doses, would not increase protection of human health; instead, it will only lead to onerous and disproportionate restrictions being placed on the use of this substance.
Topics: Female; Rats; Humans; Pregnancy; Animals; Chelating Agents; Zinc; Pentetic Acid
PubMed: 38070761
DOI: 10.1016/j.yrtph.2023.105540 -
Journal of Nuclear Medicine : Official... Sep 1998Indium-111-labeled diethylenetriamine pentaacetic acid (DTPA)-folate was evaluated as a radiopharmaceutical for targeting tumor-associated folate receptors. (Comparative Study)
Comparative Study
UNLABELLED
Indium-111-labeled diethylenetriamine pentaacetic acid (DTPA)-folate was evaluated as a radiopharmaceutical for targeting tumor-associated folate receptors.
METHODS
Athymic mice were subcutaneously inoculated with approximately 1.8 x 10(6) folate receptor-positive KB (human nasopharyngeal carcinoma) cells, yielding 0.2- to 0.6-g tumors in 15 days, at which time (111)In-DTPA-folate, (111)In-DTPA or (111)In-citrate was administered by intravenous injection.
RESULTS
The (111)In-DTPA-folate conjugate afforded marked tumor-specific (111)In deposition in vivo using this mouse model. The involvement of the folate receptor in mediating tumor uptake of (111)In-DTPA-folate was demonstrated by the blocking of tumor uptake by coadministration of free folic acid (intravenous). The (111)In-DTPA-folate also shows folate receptor-mediated uptake and retention in the kidneys, presumably reflecting radiotracer binding to folate receptors of the proximal tubules. In control experiments, the (111)In-citrate radiopharmaceutical precursor was also shown to afford significant tumor uptake of (111)In, but with much poorer tumor-to-background tissue contrast than that obtained with (111)In-DTPA-folate. Unconjugated (111)In-DTPA showed no tumor affinity.
CONCLUSION
Indium-111-DTPA-folate appears suitable as a radiopharmaceutical for targeting tumor-associated folate receptors.
Topics: Animals; Carrier Proteins; Feasibility Studies; Folate Receptors, GPI-Anchored; Folic Acid; Humans; Indium Radioisotopes; KB Cells; Kidney Tubules, Proximal; Mice; Mice, Nude; Neoplasm Transplantation; Pentetic Acid; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Cell Surface; Tissue Distribution
PubMed: 9744347
DOI: No ID Found -
International Journal of Nanomedicine 2020Multimodal imaging agent has the potential to overcome the shortage and incorporate the advantages of different imaging tools for extremely sensitive diagnosis. To...
INTRODUCTION
Multimodal imaging agent has the potential to overcome the shortage and incorporate the advantages of different imaging tools for extremely sensitive diagnosis. To achieve multimodal imaging, combining multiple contrast agents into a special nanostructure has become a main strategy; However, the combination of all of these functions into one nanoplatform usually requires a complicated synthetic procedure that results in heterogeneous nanostructure.
METHODS
In this study, we develop ultrasmall gold nanoclusters with 15 gold atoms (AuNCs) functionalized with diethylenetriamine-pentaacetic acid dianhydride (DTPAA-Gd) as an optimized multimodal imaging agent to enhance imaging ability.
RESULTS
The AuNCs-DTPAA-Gd nanohybrids possess the ultra-small size and are capable of enhancing the contrast in near-infrared fluorescence (NIRF), magnetic resonance (MR) and X-ray computed tomography (CT) imaging. Meanwhile, the integrated DTPAA-Gd component not only endow the nanohybrids to produce higher T relaxivity (r = 21.4 mM s) than Omnipaque (r = 3.973 mMs) but also further enhance X-ray attenuation property of AuNCs. Importantly, the fluorescence intensity of AuNCs-DTPAA-Gd did not decrease compared with AuNCs. Ultimately, in vivo imaging experiments have demonstrated that AuNCs-DTPAA-Gd nanohybrids can be quickly eliminated from the body through the urinary system and has great potential for anatomical imaging.
CONCLUSION
These data manifest AuNCs-DTPAA-Gd present great potential as a multimodal contrast agent for disease diagnosis, especially for early accurate detection of tumors.
Topics: Anhydrides; Animals; Contrast Media; Fluorescence; Gadolinium; Gold; HEK293 Cells; Hep G2 Cells; Humans; Magnetic Resonance Imaging; Mice, Inbred BALB C; Multimodal Imaging; Nanocomposites; Pentetic Acid; Polyamines; Spectroscopy, Near-Infrared; Tissue Distribution; Tomography, X-Ray Computed
PubMed: 32021176
DOI: 10.2147/IJN.S227169 -
Journal of the American Society For... Jan 2007A high-performance liquid chromatography-electrospray ionization/mass spectrometry (time of flight) method has been developed for the simultaneous determination of...
A high-performance liquid chromatography-electrospray ionization/mass spectrometry (time of flight) method has been developed for the simultaneous determination of synthetic Fe(III)-chelates used as fertilizers. Analytes included the seven major Fe(III)-chelates used in agriculture, Fe(III)-EDTA, Fe(III)-DTPA, Fe(III)-HEDTA, Fe(III)-CDTA, Fe(III)-o,oEDDHA, Fe(III)-o,pEDDHA, and Fe(III)-EDDHMA, and the method was validated using isotope labeled (57)Fe(III)-chelates as internal standards. Calibration curves had R values in the range 0.9962-0.9997. Limits of detection and quantification were in the ranges 3-164 and 14-945 pmol, respectively. Analyte concentrations could be determined between the limits of quantification and 25 muM (racemic and meso Fe(III)-o,oEDDHA and Fe(III)-EDDHMA) or 50 muM (Fe(III)-EDTA, Fe(III)-HEDTA, Fe(III)-DTPA, Fe(III)-CDTA and Fe(III)-o,pEDDHA). The average intraday repeatability values were approximately 0.5 and 5% for retention time and peak area, respectively, whereas the interday repeatability values were approximately 0.7 and 8% for retention time and peak area, respectively. The method was validated using four different agricultural matrices, including nutrient solution, irrigation water, soil solution, and plant xylem exudates, spiked with Fe(III)-chelate standards and their stable isotope-labeled corresponding chelates. Analyte recoveries found were in the ranges 92-101% (nutrient solution), 89-102% (irrigation water), 82-100% (soil solution), and 70-111% (plant xylem exudates). Recoveries depended on the analyte, with Fe(III)-EDTA and Fe(III)-DTPA showing the lowest recoveries (average values of 87 and 88%, respectively, for all agricultural matrices used), whereas for other analytes recoveries were between 91 and 101%. The method was also used to determine the real concentrations of Fe(III)-chelates in commercial fertilizers. Furthermore, the method is also capable of resolving two more synthetic Fe(III)-chelates, Fe(III)-EDDHSA and Fe(III)-EDDCHA, whose exact quantification is not currently possible because of lack of commercial standards.
Topics: Agriculture; Chromatography, High Pressure Liquid; Edetic Acid; Ethylenediamines; Ferric Compounds; Fertilizers; Iron Chelating Agents; Pentetic Acid; Spectrometry, Mass, Electrospray Ionization
PubMed: 17010641
DOI: 10.1016/j.jasms.2006.08.018 -
Nuclear Medicine and Biology Sep 2016To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal (90)Y. (Comparative Study)
Comparative Study
OBJECTIVES
To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal (90)Y.
METHODS
The bifunctional chelators p-SCN-Bn-H4octapa and p-SCN-Bn-CHX-A″-DTPA were conjugated to the HER2-targeting antibody trastuzumab. The resulting immunoconjugates were radiolabeled with (90)Y to compare radiolabeling efficiency, in vitro and in vivo stability, and in vivo performance in a murine model of ovarian cancer.
RESULTS
High radiochemical yields (>95%) were obtained with (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab after 15min at room temperature. Both (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab exhibited excellent in vitro and in vivo stability. Furthermore, the radioimmunoconjugates displayed high tumoral uptake values (42.3±4.0%ID/g for (90)Y-CHX-A″-DTPA-trastuzumab and 30.1±7.4%ID/g for (90)Y-octapa-trastuzumab at 72h post-injection) in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. Finally, (90)Y radioimmunotherapy studies performed in tumor-bearing mice demonstrated that (90)Y-CHX-A″-DTPA-trastuzumab and (90)Y-octapa-trastuzumab are equally effective therapeutic agents, as treatment with both radioimmunoconjugates yielded substantially decreased tumor growth compared to controls.
CONCLUSIONS
Ultimately, this work demonstrates that the acyclic chelators CHX-A″-DTPA and H4octapa have comparable radiolabeling, stability, and in vivo performance, making them both suitable choices for applications requiring (90)Y.
Topics: Animals; Cell Line, Tumor; Cell Transformation, Neoplastic; Chelating Agents; Ethylamines; Female; Isothiocyanates; Isotope Labeling; Mice; Pentetic Acid; Positron-Emission Tomography; Pyridines; Radioimmunotherapy; Tissue Distribution; Trastuzumab; Yttrium Radioisotopes
PubMed: 27419360
DOI: 10.1016/j.nucmedbio.2016.06.004 -
PloS One 2019The lanthanides (Ln3+), or rare earth elements, have proven to be useful tools for biomolecular NMR, X-ray crystallographic, and fluorescence analyses due to their...
The lanthanides (Ln3+), or rare earth elements, have proven to be useful tools for biomolecular NMR, X-ray crystallographic, and fluorescence analyses due to their unique 4f orbitals. However, their utility in biological applications has been limited because site-specific incorporation of a chelating element is required to ensure efficient binding of the free Ln3+ ion. Additionally, current Ln3+ chelator syntheses complicate efforts to directly incorporate Ln3+ chelators into proteins as the multi-step processes and a reliance on organic solvents promote protein denaturation and aggregation which are generally incompatible with direct incorporation into the protein of interest. To overcome these limitations, herein we describe a two-step aqueous synthesis of a small molecule lanthanide chelating agent amenable to site-specific incorporation into a protein using copper-free click chemistry with unnatural amino acids. The bioconjugate combines a diethylenetriaminepentaacetic acid (DTPA) chelating moiety with a clickable dibenzylcyclooctyne-amine (DBCO-amine) to facilitate the reaction with an azide containing unnatural amino acid. Incorporating the DBCO-amine avoids the use of the cytotoxic Cu2+ ion as a catalyst. The clickable lanthanide chelator (CLC) reagent reacted readily with p-azidophenylalanine (paF) without the need of a copper catalyst, thereby demonstrating proof-of-concept. Implementation of the orthogonal click chemistry reaction has the added advantage that the chelator can be used directly in a protein labeling reaction, without the need of extensive purification. Given the inherent advantages of Cu2+-free click chemistry, aqueous synthesis, and facile labeling, we believe that the CLC will find abundant use in both structural and biophysical studies of proteins and their complexes.
Topics: Chelating Agents; Click Chemistry; Copper; Iron; Lanthanoid Series Elements; Pentetic Acid; Small Molecule Libraries
PubMed: 30917122
DOI: 10.1371/journal.pone.0209726 -
TheScientificWorldJournal Aug 2007Lime and humic acid application can play an important role in the availability of zinc in paddy soils. We conducted laboratory incubation experiments on a rice growing...
Lime and humic acid application can play an important role in the availability of zinc in paddy soils. We conducted laboratory incubation experiments on a rice growing soil (Alfisol) to determine the effect of lime, humic acid and different moisture regimes on the availability of Zn. Addition of half doses of liming material (powdered lime stone) recorded highest values of DTPA-Zn followed by no lime and 100% of lime requirement throughout the incubation period. With the progress of incubation, DTPA-Zn increased slightly during the first week and then decreased thereafter. The highest DTPA-extractable Zn content of 2.85 mg/kg was found in the treatment Zn10 L1/2 at 7 days of incubation, showing 17.3 % increase in DTPA-Zn content over its corresponding treatment of Zn alone (Zn10L0). The DTPA-Zn concentration increased with the application of humic acid compared with no humic acid throughout 35 days of the incubation period and the peak value obtained was 3.12 mg/kg in the treatment Zn10 HA2 at 14 days after incubation, showing 50 % increase in Zn content over its corresponding treatment of Zn alone (Zn10HA0). The application of 0.2% humic acid compared with 0.1% resulted in greater increase in DTPA-Zn concentration in soil application. During the 35 days of incubation, highest values of DTPA-Zn were recorded in soil maintained at saturated compared to water logged conditions. However, under alternate wetting and drying condition the DTPA-Zn content gradually decreased up to 21 days and thereafter increased slowly.
Topics: Calcium Compounds; Humic Substances; Oxides; Pentetic Acid; Soil; Water; Zinc
PubMed: 17704853
DOI: 10.1100/tsw.2007.192 -
Investigative Radiology Jan 2022The aim of this study was to investigate the feasibility of measuring early changes in serum cytokine levels after intravenous diethylenetriaminepentaacetic acid...
PURPOSE
The aim of this study was to investigate the feasibility of measuring early changes in serum cytokine levels after intravenous diethylenetriaminepentaacetic acid (Ca-DTPA) chelation in patients manifesting either gadolinium deposition disease (GDD) or gadolinium storage condition (GSC) and the possible usefulness of this method in further research.
METHODS
Four patients with recent-onset GDD (≤1 year) and 2 patients with long-standing GSC (4 and 9 years) underwent chelation with intravenous bolus administration of Ca-DTPA. Multiple blood draws were performed to measure serum cytokines: at T = 0 (before Ca-DTPA injection) and 1, 5, 10, 30, 60 minutes, and 24 hours after Ca-DTPA injection. Patients rated the severity of GDD symptom flare at 24 hours. The 24-hour urine Gd amounts were measured prechelation and for the 24 hours after chelation. Serum samples were analyzed blind to whether patients had GDD or GSC but with knowledge of the time points characterizing each sample.
RESULTS
Urine samples for both GDD and GSC patients showed increases in Gd postchelation. All GDD patients experienced flare reactions postchelation; the 2 GSC patients did not. Two cytokines, EGF and sCD40L, peaked at 30 minutes postchelation in at least 4 of the 6 participants. Three cytokines, ENA78/CXCL5, EOTAXIN/CCL11, and LEPTIN, peaked at 24 hours in at least 4 of the 6 participants. Two participants were high outliers for a large number of cytokines across time points. No clear distinction between GDD and GSC was apparent from the cytokine patterns, although differences were present.
CONCLUSIONS
This pilot study describes precise temporal resolution (in the range of minutes) after a cytokine-inciting event. Select cytokines exhibited peak values at different time points. At this preliminary stage of investigation, peak cytokine release seems to reflect the amount of Gd mobilized rather than the severity of the patient symptomatic reaction. Too few subjects were studied to support statistical analysis between GDD and GSC groups, although differences were observed through visual data analysis.
Topics: Contrast Media; Cytokines; Gadolinium; Gadolinium DTPA; Humans; Magnetic Resonance Imaging; Organometallic Compounds; Pentetic Acid; Pilot Projects
PubMed: 34120127
DOI: 10.1097/RLI.0000000000000803 -
Methods in Molecular Biology (Clifton,... 2011The use of fluorescent (or luminescent) and metal contrast agents in high-throughput screens, in vitro assays, and molecular imaging procedures has rapidly expanded in...
The use of fluorescent (or luminescent) and metal contrast agents in high-throughput screens, in vitro assays, and molecular imaging procedures has rapidly expanded in recent years. Here we describe the development and utility of high-affinity ligands for cancer theranostics and other in vitro screening -studies. In this context, we also illustrate the syntheses and use of heteromultivalent ligands as targeted imaging agents.
Topics: Animals; Binding Sites; Cell Line; Chelating Agents; Fluorescent Dyes; Heterocyclic Compounds, 1-Ring; Humans; Lanthanoid Series Elements; Ligands; Magnetic Resonance Imaging; Mice; Microscopy, Fluorescence; Molecular Imaging; Neoplasms; Pentetic Acid
PubMed: 21318902
DOI: 10.1007/978-1-61779-012-6_6