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Sample records for diethylenetriaminepentaacetic acid dtpa

  1. Convenient solid-phase synthesis of diethylenetriaminepenta-acetic acid (DTPA)- conjugated cyclic RGD peptide analogues.

    PubMed

    Wang, Wei; McMurray, John S; Wu, Qingping; Campbell, Martin L; Li, Chun

    2005-10-01

    Solid-phase synthesis of radiometal chelator-conjugated peptides can facilitate the creation of radioactive peptide libraries to be utilized in high throughput in vivo screening of targeted nuclear-imaging agents. In this study, a new diethylenetriaminepentaacetic acid (DTPA) derivative, 1-(p-succinamidobenzyl)- DTPA penta-t-butyl ester [DTPA(But)(5)-Bz-NH-SA], and its precursor molecule, 1-(p-aminobenzyl)- DTPA penta-t-butyl ester (DTPA(But)(5)-Bz-NH(2)), were applied to the solid-phase synthesis of DTPA-conjugated cyclic peptides containing the Arg-Gly-Asp (RGD) motif with high efficiency. The resulting conjugates, DTPA-Bz-NH-SA-c(Lys-Arg-Gly-Asp-phe) [DTPA-Bz-NH-SA-c(KRGDf)] and DTPA-Bz-NHc( Glu-Arg-Gly-Asp-phe) [DTPA-Bz-NH-c(KRGDf)], demonstrated similar in vitro biologic activities as their corresponding parent peptides. (111)In-labeled, DTPA-conjugated RGD peptides showed selective binding to integrin alphavbeta3 in human melanoma M21 tumors grown in nude mice. Furthermore, (111)In-DTPABz- NH-c(ERGDf) showed lower retention in the liver and the kidney than (111)In-DTPA-Bz-NH-SAc( KRGDf) did, which contributed to higher target to nontarget ratio for (111)In-DTPA-Bz-NH-c(ERGDf). The method reported here can be extended to the construction of peptide libraries containing DTPA for high throughput in vitro and in vivo screening of molecularly targeted imaging agents.

  2. Solid dispersions of the penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA): formulation design and optimization studies.

    PubMed

    Yang, Yu-Tsai; Di Pasqua, Anthony J; Zhang, Yong; Sueda, Katsuhiko; Jay, Michael

    2014-11-01

    The penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was incorporated into a solid dispersion for oral administration by the solvent evaporation method using blends of polyvinylpyrrolidone (PVP), Eudragit® RL PO and α-tocopherol. D-optimal mixture design was used to optimize the formulation. Formulations that had a high concentration of both Eudragit® RL PO and α-tocopherol exhibited low water absorption and enhanced stability of the DTPA prodrug. Physicochemical properties of the optimal formulation were evaluated using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). In vitro release of the prodrug was evaluated using the USP Type II apparatus dissolution method. DSC studies indicated that the matrix had an amorphous structure, while FTIR spectrometry showed that DTPA penta-ethyl ester and excipients did not react with each other during formation of the solid dispersion. Dissolution testing showed that the optimized solid dispersion exhibited a prolonged release profile, which could potentially result in a sustained delivery of DTPA penta-ethyl to enhance bioavailability. In conclusion, DTPA penta-ethyl ester was successfully incorporated into a solid matrix with high drug loading and improved stability compared to prodrug alone.

  3. Solid dispersions of the penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA): Formulation design and optimization studies

    PubMed Central

    Yang, Yu-Tsai; Di Pasqua, Anthony J.; Zhang, Yong; Sueda, Katsuhiko; Jay, Michael

    2015-01-01

    The penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was incorporated into a solid dispersion for oral administration by the solvent evaporation method using blends of polyvinylpyrrolidone (PVP), Eudragit® RL PO and α-tocopherol. D-optimal mixture design was used to optimize the formulation. Formulations that had a high concentration of both Eudragit® RL PO and α-tocopherol exhibited low water absorption and enhanced stability of the DTPA prodrug. Physicochemical properties of the optimal formulation were evaluated using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). In vitro release of the prodrug was evaluated using the USP Type II apparatus dissolution method. DSC studies indicated that the matrix had an amorphous structure, while FTIR spectrometry showed that DTPA penta-ethyl ester and excipients did not react with each other during formation of the solid dispersion.. Dissolution testing showed that the optimized solid dispersion exhibited a prolonged release profile, which could potentially result in a sustained delivery of DTPA penta-ethyl to enhance bioavailability. In conclusion, DTPA penta-ethyl ester was successfully incorporated into a solid matrix with high drug loading and improved stability compared to prodrug alone. PMID:24047113

  4. Tc-99 m diethylenetriamine-pentaacetic acid (DTPA): is it reliable for assessment of methotrexate-induced cumulative effect on renal filtration in rheumatoid arthritis patients?

    PubMed

    Amin, Amr; Effat, Dina; Goher, Nabila; Ramadan, Basma

    2013-12-01

    Methotrexate (MTX) is commonly employed as the initial DMARD used for the treatment of rheumatoid arthritis (RA). We aimed to contribute to the safety profile of MTX by assessing its cumulative effect on renal filtration. A total of 52 RA adult female patients with normal baseline serum creatinine and GFR at the initial diagnosis of the disease were included. Group 1 (G1) included 30 patients (mean age 40.4 ± 4.4 years) on MTX and NSAIDS, while 22 RA patients (mean age 38.5 ± 8.2 years) who received NSAIDs only served as control group (G2). Renal function was assessed by GFR measurement using technetium diethylenetriamine-pentaacetic acid (Tc-99 m DTPA) at a point of the study time corresponding to disease duration. Twenty-one out of thirty (70 %) in G1 showed reduced GFR compared to 6/22 (27.3 %) in G2 (P = 0.007), with 3.3 ± 0.5 % annual reduction in GFR. Reduced GFR in G1 showed significant negative correlation with age (r = -0.396, P = 0.005), MTX cumulative dose (r = -0.263, P = 0.049), MTX-intake duration (r = -0.293, P = 0.031) and NSAIDs-intake duration (r = -0.344, P = 0.014). Low-dose MTX has a slow cumulative effect on renal filtration manifested by GFR reduction overtime that could be monitored by Tc-99 m DTPA.

  5. Decorporation of systemically distributed americium by a novel orally administered diethylenetriaminepentaacetic acid (DTPA) formulation in beagle dogs.

    PubMed

    Wilson, James P; Cobb, Ronald R; Dungan, Nathanael W; Matthews, Laura L; Eppler, Bärbel; Aiello, Kenneth V; Curtis, Shiro; Boger, Teannetta; Guilmette, Raymond A; Weber, Waylon; Doyle-Eisele, Melanie; Talton, James D

    2015-03-01

    Novel decorporation agents are being developed to protect against radiological accidents and terrorists attacks. Radioactive americium is a significant component of nuclear fallout. Removal of large radioactive materials, such as 241Am, from exposed persons is a subject of significant interest due to the hazards they pose. The objective of this study was to evaluate the dose-related efficacy of daily doses of NanoDTPA™ Capsules for decorporating Am administered intravenously as a soluble citrate complex to male and female beagle dogs. In addition, the efficacy of the NanoDTPA™ Capsules for decorporating 241Am was directly compared to intravenously administered saline and DTPA. Animals received a single IV administration of 241Am(III)-citrate on Day 0. One day after radionuclide administration, one of four different doses of NanoDTPA™ Capsules [1, 2, or 6 capsules d(-1) (30 mg, 60 mg, or 180 mg DTPA) or 2 capsules BID], IV Zn-DTPA (5 mg kg(-1) pentetate zinc trisodium) as a positive control, or IV saline as a placebo were administered. NanoDTPA™ Capsules, IV Zn-DTPA, or IV saline was administered on study days 1-14. Animals were euthanized on day 21. A full necropsy was conducted, and liver, spleen, kidneys, lungs and trachea, tracheobronchial lymph nodes (TBLN), muscle samples (right and left quadriceps), gastrointestinal (GI) tract (stomach plus esophagus, upper and lower intestine), gonads, two femurs, lumbar vertebrae (L1-L4), and all other soft tissue remains were collected. Urinary and fecal excretion profiles were increased approximately 10-fold compared to those for untreated animals. Tissue contents were decreased compared to untreated controls. In particular, liver content was decreased by approximately eightfold compared to untreated animals. The results from this study further demonstrate that oral NanoDTPA™ Capsules are equally efficient compared to IV Zn-DTPA in decorporation of actinides.

  6. Gd complexes of macrocyclic diethylenetriaminepentaacetic acid (DTPA) biphenyl-2,2'-bisamides as strong blood-pool magnetic resonance imaging contrast agents.

    PubMed

    Jung, Ki-Hye; Kim, Hee-Kyung; Lee, Gang Ho; Kang, Duk-Sik; Park, Ji-Ae; Kim, Kyeong Min; Chang, Yongmin; Kim, Tae-Jeong

    2011-08-11

    We report the synthesis of macrocyclic DTPA conjugates of 2,2'-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H(2)O)]·xH(2)O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R(1) relaxivity reaches 10.9 mM(-1) s(-1), which is approximately 3 times as high as that of structurally related Gd-DOTA (R(1) = 3.7 mM(-1) s(-1)). The R(1) relaxivity in HSA goes up to 37.2 mM(-1) s(-1), which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2b are coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2 is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect.

  7. Preparation of alginate beads containing a prodrug of diethylenetriaminepentaacetic acid

    PubMed Central

    Yang, Yu-Tsai; Di Pasqua, Anthony J.; He, Weiling; Tsai, Tsuimin; Sueda, Katsuhiko; Zhang, Yong; Jay, Michael

    2012-01-01

    A penta-ethyl ester prodrug of the radionuclide decorporation agent diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was encapsulated in alginate beads by the ionotropic gelation method. An optimal formulation was found by varying initial concentrations of DTPA pentaethyl ester, alginate polymer, Tween 80 surfactant and calcium chloride. All prepared alginate beads were ~1.6 mm in diameter, and the optimal formulation had loading and encapsulation efficiencies of 91.0 ± 1.1 and 72.6 ± 2.2%, respectively, and only 3.2 ± 0.8% water absorption after storage at room temperature in ~80% relative humidity. Moreover, Fourier transform infrared spectroscopy showed that DTPA penta-ethyl ester did not react with excipients during formation of the DTPA penta-ethyl ester-containing alginate beads. Release of prodrug from alginate beads was via anomalous transport, and its stability enhanced by encapsulation. Collectively, these data suggest that this solid dosage form may be suitable for oral administration after radionuclide contamination. PMID:23399237

  8. Selective two-step titration of thorium by sulfate displacement of the diethylenetriaminepentaacetic acid complex

    SciTech Connect

    Kiefer, P.

    1980-07-01

    Thorium and other metals are complexed with excess diethylenetriaminepentaacetic acid (DTPA) at pH 1.4, the excess DTPA is titrated with Bi(III) to a xylenol orange end point, sulfate is added to complex Th(IV), and the displaced DTPA again is titrated with Bi(III). Of 61 metal ions and nonmetal anions tested, only Ga(III), Sc(III), tungstate, citrate, oxalate, and thiosulfate interfere seriously. Lesser interferences are In(III), Zr(IV), V(IV), and permanganate. The standard deviation is 2 ..mu..g for 56 to 840 ..mu..g Th.

  9. Thermodynamic, spectroscopic, and computational studies of lanthanide complexation with Diethylenetriaminepentaacetic acide: temperature effect and coordination modes

    SciTech Connect

    Guoxin Tian; Leigh R. Martin; Zhiyong Zhang; Linfeng Rao

    2011-04-01

    Stability constants of two DTPA (diethylenetriaminepentaacetic acid) complexes with lanthanides (ML2- and MHL-, where M stands for Nd and Eu and L stands for diethylenetriaminepentaacetate) at 10, 25, 40, 55, and 70 degrees C were determined by potentiometry, absorption spectrophotometry, and luminescence spectroscopy. The enthalpies of complexation at 25 degrees C were determined by microcalorimetry. Thermodynamic data show that the complexation of Nd3þ and Eu3þ with DTPA is weakened at higher temperatures, a 10-fold decrease in the stability constants of ML2- and MHL- as the temperature is increased from 10 to 70 degrees C. The effect of temperature is consistent with the exothermic enthalpy of complexation directly measured by microcalorimetry. Results by luminescence spectroscopy and density functional theory (DFT) calculations suggest that DTPA is octa-dentate in both the EuL2- and EuHL- complexes and, for the first time, the coordination mode in the EuHL- complex was clarified by integration of the experimental data and DFT calculations. In the EuHL- complex, the Eu is coordinated by an octa-dentate H(DTPA) ligand and a water molecule, and the protonation occurs on the oxygen of a carboxylate group.

  10. Separation Nanotechnology of Diethylenetriaminepentaacetic Acid Bonded Magnetic Nanoparticles for Spent Nuclear Fuel

    SciTech Connect

    Kaur, Maninder; Johnson, Andrew; Tian, Guoxin; Jiang, Weilin; Rao, Linfeng; Paszczynski, Andrzej; Qiang, You

    2013-01-01

    A nanomagnetic separation method based on Diethylenetriaminepentaacetic acid (DTPA) conjugated with magnetic nanoparticles (MNPs) is studied for application in spent nuclear fuel separation. The high affinity of DTPA towards actinides aids in separation from the highly acidic medium of nuclear waste. The solubility and magnetization of particles at low pH is protected by encapsulating them in silica layer. Surface functionalization of silica coated particles with polyamines enhances the loading capacity of the chelators on MNPs. The particles were characterized before and after surface modification using transmission electron microscopy (TEM), helium ion microscopy (HIM), Fourier transform-infrared (FT-IR) spectrometry, and X-ray diffractometry. The coated and uncoated samples were studied using vibrating sample magnetometer (VSM) to understand the change in magnetic properties due to the influence of the surface functionalization. The hydrodynamic size and surface charge of the particles are investigated using Dynamic Light Scattering (DLS). The uptake behavior of Am(III), Pu(IV), U(VI), and Np(V) from 0.1M NaNO3 solution was investigated. The sorption result shows the strong affinity of DTPA towards Am(III) and Pu(IV) by extracting 97% and 80% of actinides, respectively. The high removal efficiency and fast uptake of actinides make the chelator conjugated MNPs an effective method for spent nuclear fuel separation.

  11. Change in renal function following laparoscopic donor nephrectomy using 99 mTc-diethylenetriaminepentaacetic acid scan.

    PubMed

    Cho, Hyuk Jin; Choi, Sae Woong; Bae, Woong Jin; Kim, Su Jin; Hong, Sung Hoo; Lee, Ji Youl; Kim, Sae Woong; Hwang, Tae-Kon

    2015-05-01

    We assessed the change in remaining kidney function after laparoscopic donor nephrectomy using serial technetium 99m diethylenetriaminepentaacetic acid (DTPA) scans and investigated the factors affecting the course. Data from 155 donors were obtained from a prospectively maintained database. All donors underwent consecutive DTPA scans preoperatively and 1 month, 6 months and 1 year postoperatively. We investigated the longitudinal change in renal function after surgery and analyzed parameters to influence the perioperative glomerular filtration rate (GFR) change. The changes in GFR according to the DTPA scan presented significant improvement from 1 month up to 2 years after donation (all p < 0.001). The DTPA-GFR of the remaining kidney increased by 14.8% to 58.2 ± 10.6 ml/min/1.73 m(2) (p < 0.001) and by 33.9% to 78.0 ± 14.0 ml/min/1.73 m(2) at 1 month and 1 year after surgery, respectively (p < 0.001). Only 21.9% of donors categorized into chronic kidney disease (CKD) stage 3 or more at 1 year after donation were <60 ml/min/1.73 m(2) according to DTPA-GFR. Multivariate regression analysis revealed that the increase in DTPA-GFR at 1 year was negatively associated with patient age (p = 0.005), BMI (p = 0.04) and preoperative DTPA-GFR of remaining kidney (p = 0.009). The DTPA-GFR of remaining kidney increased steadily for up to 2 years after surgery. Younger donors with lower body mass index and those with lower initial function of the remaining kidney demonstrated a greater increase in DTPA-GFR after nephrectomy. Many of the donors with CKD stage 3 after donation have good renal function according to the results of DTPA-GFR.

  12. Fluorescence-enhanced europium-diethylenetriaminepentaacetic (DTPA)-monoamide complexes for the assessment of renal function.

    PubMed

    Chinen, Lori K; Galen, Karen P; Kuan, K T; Dyszlewski, Mary E; Ozaki, Hiroaki; Sawai, Hiroaki; Pandurangi, Raghootama S; Jacobs, Frederick G; Dorshow, Richard B; Rajagopalan, Raghavan

    2008-02-28

    Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we have prepared and evaluated Eu(3+) complexes of several diethylenetriamine pentaacetate (DTPA)-monoamide ligands bearing molecular "antennae" to enhance metal fluorescence via intramolecular ligand-metal fluorescence resonance energy transfer process. The results show that Eu-DTPA-monoamide complex 18b, which contains a quinoxanlinyl antenna, exhibits large (ca. 2700-fold) Eu(3+) fluorescence enhancement. Indeed, complex 18b exhibits the highest fluorescent enhancement observed thus far in the DTPA-type metal complexes. The renal clearance property was assessed using the corresponding radioactive (111)In complex 18a, and the data suggest that this complex clears via a complex mechanism that includes glomerular filtration.

  13. Use of /sup 99m/Tc diethylenetriaminepentaacetic acid for assessment of renal function in dogs with suspected renal disease

    SciTech Connect

    Krawiec, D.R.; Twardock, A.R.; Badertscher, R.R. II; Daniel, G.B.; Dugan, S.J.

    1988-04-15

    The effectiveness of technetium /sup 99m/-labeled diethylenetriaminepentaacetic acid (/sup 99m/Tc DTPA) to assess renal function in 13 dogs with suspected renal disease was evaluated. Glomerular filtration rates (actual GFR) were determined on the basis of endogenous creatinine clearance. Predicted GFR were determined by using /sup 99m/Tc DTPA within 72 hours after the determination of creatinine clearance. The percentage of an IV administered dose of /sup 99m/Tc DTPA in the kidneys (percentage dose) was determined. Two equations were used to calculate predicted GFR, which were derived from previously reported linear regression analysis of inulin (In) and creatinine (Cr) GFR vs percentage dose /sup 99m/Tc DTPA in dog kidneys. The correlations of actual GFR vs predicted GFR (In) and actual GFR vs predicted GFR (Cr) were both r = 0.92. The dogs' mean actual GFR was 1.73 +/- 1.35 ml/min/kg. Their mean predicted GFR (In) and predicted GFR (Cr) were 1.92 +/- 1.42 ml/min/kg and 1.85 +/- 1.27 ml/min/kg, respectively. Therefore, /sup 99m/Tc DTPA can be used with high accuracy as an agent to predict GFR in dogs with suspected renal disease. The procedure for determining GFR by use of nuclear medicine was rapid and noninvasive and appeared to induce little stress in the animals evaluated.

  14. Comparative evaluation of glutamate-sensitive radiopharmaceuticals: Technetium-99m-glutamic acid and technetium-99m-diethylenetriaminepentaacetic acid-bis(glutamate) conjugate for tumor imaging.

    PubMed

    Kakkar, Dipti; Tiwari, Anjani K; Chuttani, Krishna; Kaul, Ankur; Singh, Harpal; Mishra, Anil K

    2010-12-01

    Single-photon emission computed tomography has become a significant imaging modality with huge potential to visualize and provide information of anatomic dysfunctions that are predictive of future diseases. This imaging tool is complimented by radiopharmaceuticals/radiosubstrates that help in imaging specific physiological aspects of the human body. The present study was undertaken to explore the utility of technetium-99m (⁹⁹(m)Tc)-labeled glutamate conjugates for tumor scintigraphy. As part of our efforts to further utilize the application of chelating agents, glutamic acid was conjugated with a multidentate ligand, diethylenetriaminepentaacetic acid (DTPA). The DTPA-glutamate conjugate [DTPA-bis(Glu)] was well characterized by IR, NMR, and mass spectroscopy. The biological activity of glutamic acid was compared with its DTPA conjugate by radiocomplexation with ⁹⁹(m)Tc (labeling efficiency ≥98%). In vivo studies of both the radiolabeled complexes ⁹⁹(m)Tc-Glu and ⁹⁹(m)Tc-DTPA-bis(Glu) were then carried out, followed by gamma scintigraphy in New Zealand albino rabbits. Improved serum stability of ⁹⁹(m)Tc-labeled DTPA conjugate indicated that ⁹⁹(m)Tc remained bound to the conjugate up to 24 hours. Blood clearance showed a relatively slow washout of the DTPA conjugate when compared with the labeled glutamate. Biodistribution characteristics of the conjugate in Balb/c mice revealed that DTPA conjugation of glutamic acid favors less accumulation in the liver and bone and rapid renal clearance. Tumor scintigraphy in mice showed increasing tumor accumulation, stable up to 4 hours. These preliminary studies show that ⁹⁹(m)Tc-DTPA-bis(Glu) can be a useful radiopharmaceutical for diagnostic applications in single-photon emission computed tomography imaging.

  15. Ligand-modified polyelectrolyte-enhanced ultrafiltration with electrostatic attachment of ligands. 2. Use of diethylenetriaminepentaacetic acid/cationic polyelectrolyte mixtures to remove both cations and anions from aqueous streams

    SciTech Connect

    Tuncay, M. Univ. of Oklahoma, Norman, OK ); Christian, S.D.; Tucker, E.E.; Taylor, R.W.; Scamehorn, J.F. )

    1994-12-01

    A mixture of a cationic polyelectrolyte, poly(diallyldimethylammonium chloride) or PDADMAC, and the anionic ligand diethylenetriaminepentaacetic acid (DTPA) can be added to aqueous streams as a water-soluble colloid to bind simultaneously divalent cations, such as Cu[sup 2+] and Pb[sup 2+], and anions, such as CrO[sub 4][sup 2[minus

  16. A novel DTPA cross-linking of hyaluronic acid and metal complexation thereof.

    PubMed

    Buffa, Radovan; Běťák, Jiří; Kettou, Sofiane; Hermannová, Martina; Pospíšilová, Lucie; Velebný, Vladimír

    2011-09-27

    Macromolecular conjugates of a natural polysaccharide, hyaluronic acid, with diethylenetriaminepentaacetic acid (DTPA)-metal complexes were synthesized and characterized by FTIR, NMR, SEC-MALLS and ICP analysis. Several parameters of the cross-linking reaction as molecular weight of starting HA, temperature, equivalent of DTPA bis-anhydride, concentration of HA, presence of transacylation catalyst DMAP and reaction time were studied. The mechanism for the reaction was suggested and relationship between the molecular weight assigned by SEC-MALLS, reaction parameters and rheological properties of the final cross-linked products were investigated. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Effect of captopril on 99mTc-diethylenetriaminepentaacetic acid renograms in two-kidney, one clip hypertension

    SciTech Connect

    Nally, J.V. Jr.; Clarke, H.S. Jr.; Grecos, G.P.; Saunders, M.; Gross, M.L.; Potvin, W.J.; Windham, J.P.

    1986-08-01

    In an effort to improve on the noninvasive detection of renal artery stenosis, we investigated the effect of angiotensin converting enzyme inhibition on computer-assisted /sup 99m/Tc-diethylenetriaminepentaacetic acid (DTPA) renal flow studies in a canine model of two-kidney, one clip hypertension and compared these findings with clearances of inulin and p-aminohippuric acid in the stenotic and contralateral kidney before and after converting enzyme inhibition. The /sup 99m/Tc-DTPA renal flow study with the converting enzyme inhibitor captopril (1.5 mg/kg bolus with 1.5 mg/min infusion) showed an increased sensitivity in the detection of unilateral renal artery stenosis over the use of the /sup 99m/Tc-DTPA study alone. Captopril induced striking alterations that were most evident in the 15-minute /sup 99m/Tc-DTPA renal flow study, in which all nine curves exhibited severely blunted uptake and excretion of the radionuclide. These changes were reversed during a recovery study without converting enzyme inhibition and were not seen when blood pressure was lowered with nitroprusside to a level similar to that observed during converting enzyme inhibition. The changes shown by the /sup 99m/Tc-DTPA study during converting enzyme inhibition correlated with a decrease in the glomerular filtration rate of the stenotic kidney. Captopril infusion significantly decreased the glomerular filtration rate of the stenotic kidney (16.0 +/- 3.1 vs 11.0 +/- 2.5 mg/min, p less than 0.03) but not of the contralateral kidney (32.4 +/- 2.6 vs 28.4 +/- 2.8 mg/min).

  18. Extraction of rare earth metals with 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester in the presence of diethylenetriaminepentaacetic acid in aqueous phase

    SciTech Connect

    Kubota, Fukiko; Goto, Masahiro; Nakashio, Fumiyuki

    1993-07-01

    The extraction equilibria of rare earth metals with 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (commercial name, PC-88A, henceforth abbreviated as HR) dissolved in n-heptane were measured at 303 K. It was found that rare earth metals are extracted with the dimer of the extractant, (HR){sub 2}, as follows. M{sub aq}{sup 3+} + 3(HR){sub 2 org} MR{sub 3} {center_dot} 3HR{sub org} + 3H{sub aq}{sup +} The extraction equilibrium constants of metals were obtained and compared with the extraction equilibrium constants obtained by di(2-ethylhexyl)phosphoric acid (henceforth DZEHPA). Furthermore, the extraction equilibria of rare earth metals with PC-88A in the presence of diethylenetriaminepentaacetic acid (henceforth DTPA) in an aqueous phase were also measured to discuss the effect of DTPA on the extraction of rare earth metals. 13 refs., 8 figs., 2 tabs.

  19. Formulation for Tin-.sup.117m /diethylenetriaminepentaacetic acids

    DOEpatents

    Srivastava, Suresh C.; Meinken, George E.

    1999-01-01

    The invention provides improved formulations of .sup.117m Sn (Sn.sup.4+) DTPA which allow higher doses of .sup.117m Sn (Sn.sup.4+) to be administered than were previously possible. Methods for making pharmaceutical compositions comprising .sup.117m Sn (Sn.sup.4+) DTPA in which the amount of unchelated DTPA is minimized are disclosed along with methods of using the improved formlulations, both for palliation of bone pain associated with cancer and for treatment of osseous tumors.

  20. Evaluation of diethylenetriaminepentaacetic acid-manganese(II) complexes modified by narrow molecular weight distribution of chitosan oligosaccharides as potential magnetic resonance imaging contrast agents.

    PubMed

    Huang, Yan; Zhang, Xiaoyan; Zhang, Qi; Dai, Xueqin; Wu, Jingbo

    2011-05-01

    Novel conjugates of narrow molecular weight distribution of chitosan oligosaccharides (CSn; n=6, 8, 11) with manganese-diethylenetriaminepentaacetic acid (Mn-DTPA) as potential magnetic resonance imaging (MRI) contrast agents were synthesized. The structures were characterized by means of Fourier transform infrared spectra, (13)C nuclear magnetic resonance, size exclusion chromatography and inductively coupled plasma atomic emission spectrometry. The characterization results showed that Mn-DTPA was successfully linked to aminated CSn by an amide function. The magnetic properties were characterized by in vitro and T(1)-weighted FLASH image experiments. Relaxivities studies indicated that Mn-DTPA-CSn (n=8, 11) provided higher relaxivity, either in aqueous or bovine serum albumin solution (0.725 mM), than commercial contrast agent Gd-DTPA. The stability results showed that Mn-DTPA-CSn in aqueous were stable enough to prevent Mn(II) ions from releasing. The preliminary in vitro and T(1)-weighted FLASH image studies suggested that Mn-DTPA-CSn had the advantage of becoming promising MRI contrast agents. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Process for the manufacture of 117Sn diethylenetriaminepentaacetic acids

    DOEpatents

    Srivastava, Suresh C.; Li, Zizhong; Meinken, George

    2003-01-01

    Novel methods are provided for the manufacture of .sup.117m Sn(Sn.sup.4+) DTPA. The method allows the use of DTPA, a toxic chelating agent, in an approximately 1:1 ratio to .sup.117m Sn(Sn.sup.4+) via either aqueous conditions, or using various organic solvents, such as methylene chloride. A pharmaceutical composition manufactured by the novel method is also provided, as well as methods for treatment of bone tumors and pain associated with bone cancer using the pharmaceutical composition of the invention.

  2. Gd complexes of diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide as a new liver-specific MRI contrast agent.

    PubMed

    Huang, Yan; Cao, Bennan; Yang, Xiaolu; Zhang, Qi; Han, Xiangjun; Guo, Ziyi

    2013-05-01

    This study was to describe the synthesis of complexes of gadolinium diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide Gd-DTPA-CSn (n=6, 8, 11) as a new class of contrast agent as well as its magnetic property in a pilot magnetic resonance imaging. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r1), FLASH imaging in phantoms in vitro and signal intensity in vivo of the rat abdominal axial imaging. The r1 of Gd-DTPA-CS11 was up to 11.65 mM(-1)·s(-1), which was 3 times higher than that of the analogous MRI contrast agent Gd-DTPA in commercial use. In vivo MR images of rat obtained with Gd-DTPA-CS11 showed strong signal enhancement in liver and the vessels of the liver parenchyma during the extended period of time. The present study suggests that the new synthesized gadolinium complexes can be used as a new class of practical liver-specific MRI contrast agent because of its superior performance compared with Gd-DTPA. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals

    PubMed Central

    de Albuquerque, Isabella Martins; Cardoso, Dannuey Machado; Masiero, Paulo Ricardo; Paiva, Dulciane Nunes; Resqueti, Vanessa Regiane; Fregonezi, Guilherme Augusto de Freitas; Menna-Barreto, Sérgio Saldanha

    2016-01-01

    ABSTRACT Objective: To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects. PMID:28117469

  4. Rapid and sensitive determination of ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid in water samples by ion-pair reversed-phase liquid chromatography--electrospray tandem mass spectrometry.

    PubMed

    Quintana, José Benito; Reemtsma, Thorsten

    2007-03-23

    A new method is presented for the quantitative determination of ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) from aqueous samples without an enrichment step. It consist of the formation of the Fe(III) complexes of EDTA and DTPA, liquid-chromatography with a volatile ion-pairing agent and determination by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Limits of quantification (LOQ) of 1.0 and 0.6 microgL(-1) for EDTA and DTPA were obtained, allowing the direct injection of most aqueous environmental samples without any preceding enrichment. With a more recent mass spectrometer, the LOQ could be further decreased by almost one order of magnitude. Parallel analysis of real samples by a standardized method employing enrichment, derivatization and GC-MS analysis yielded comparable results. The method was applied to the determination of both complexing agents in several wastewater, surface water and drinking water samples, showing that EDTA is an omnipresent contaminant in partially closed water cycles.

  5. Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals.

    PubMed

    Albuquerque, Isabella Martins de; Cardoso, Dannuey Machado; Masiero, Paulo Ricardo; Paiva, Dulciane Nunes; Resqueti, Vanessa Regiane; Fregonezi, Guilherme Augusto de Freitas; Menna-Barreto, Sérgio Saldanha

    2016-01-01

    To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects. Avaliar os efeitos da pressão expiratória positiva (PEP) na permeabilidade da membrana epitelial pulmonar em indivíduos saudáveis. Foi avaliada uma coorte de 30 indivíduos saudáveis (15 homens e 15 mulheres), com média de idade de 28,3 ± 5,4 anos, média da relação VEF1/CVF de 0,89 ± 0,14 e média de VEF1 de 98,5 ± 13,1% do previsto. Os indivíduos foram submetidos a cintilografia pulmonar por inalação de radioaerossol de ácido dietilenotriaminopentacético marcado com tecnécio-99m (99mTc-DTPA em inglês) em dois estágios: durante respiração espontânea e durante respiração com uma máscara de PEP de 10 cmH2O (n = 10), 15 cmH2O (n = 10) ou 20 cmH2O (n = 10). O 99mTc-DTPA foi nebulizado por 3 min, e sua depuração foi registrada por cintilografia por um

  6. Contrast enhancement of the brain by folate-conjugated gadolinium-diethylenetriaminepentaacetic acid-human serum albumin nanoparticles by magnetic resonance imaging.

    PubMed

    Korkusuz, Huedayi; Ulbrich, Karsten; Bihrer, Verena; Welzel, Katerina; Chernikov, Valery; Knobloch, Thomas; Petersen, Sabine; Huebner, Frank; Ackermann, Hanns; Gelperina, Svetlana; Korkusuz, Yuecel; Kromen, Wolfgang; Hammerstingl, Renate; Haupenthal, Jörg; Fiehler, Jens; Zeuzem, Stefan; Kreuter, Jörg; Vogl, Thomas J; Piiper, Albrecht

    2012-01-01

    Different from regular small molecule contrast agents, nanoparticle-based contrast agents have a longer circulation time and can be modified with ligands to confer tissue-specific contrasting properties. We evaluated the tissue distribution of polymeric nanoparticles (NPs) prepared from human serum albumin (HSA), loaded with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) (Gd-HSA-NP), and coated with folic acid (FA) (Gd-HSA-NP-FA) in mice by magnetic resonance imaging (MRI). FA increases the affinity of the Gd-HSA-NP to FA receptor-expressing cells. Clinical 3 T MRI was used to evaluate the signal intensities in the different organs of mice injected with Gd-DTPA, Gd-HSA-NP, or Gd-HSA-NP-FA. Signal intensities were measured and standardized by calculating the signal to noise ratios. In general, the NP-based contrast agents provided stronger contrasting than Gd-DTPA. Gd-HSA-NP-FA provided a significant contrast enhancement (CE) in the brain (p  =  .0032), whereas Gd-DTPA or Gd-HSA-NP did not. All studied MRI contrast agents showed significant CE in the blood, kidney, and liver (p < .05). Gd-HSA-NP-FA elicited significantly higher CE in the blood than Gd-HSA-NP (p  =  .0069); Gd-HSA-NP and Gd-HSA-NP-FA did not show CE in skeletal muscle and gallbladder; Gd-HSA-NP, but not Gd-HSA-NP-FA, showed CE in the cardiac muscle. Gd-HSA-NP-FA has potential as an MRI contrast agent in the brain.

  7. Nucleation of calcium carbonate in presence of citric acid, DTPA, EDTA and pyromellitic acid.

    PubMed

    Westin, K-J; Rasmuson, A C

    2005-02-15

    The influence of four calcium complexing additives, i.e., citric acid (CIT), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA) and pyromellitic acid (PMA), and their concentration on the induction time of calcium carbonate nucleation has been studied. The experiments were performed by rapidly mixing a sodium carbonate solution and a calcium chloride solution of various concentrations. The induction time was obtained by recording the white light absorption of the solution. Chemical speciation was used to estimate the initial thermodynamic driving force of each experiment. The induction time was found to increase with additive concentration. The effect varies from one additive to another. CIT causes the greatest increase in induction time and PMA the least. Using classical nucleation theory the experimental data were evaluated in terms of the interfacial energy. In pure water a value of 37.8 mJ m(-2) was obtained, showing good agreement with other works. CIT, DTPA and EDTA caused a notable increase of the interfacial energy at a concentration of 0.5 mmol l(-1). PMA does not appear to have any effect at all on the interfacial energy. Different mechanisms for the influence of the additives on the measured induction time and on the estimated interfacial energy are discussed.

  8. Prospective evaluation of renal allograft dysfunction with 99mtechnetium-diethylenetriaminepentaacetic acid renal scans

    SciTech Connect

    McConnell, J.D.; Sagalowsky, A.I.; Lewis, S.E.; Gailiunas, P.; Helderman, J.H.; Dawidson, I.; Peters, P.C.

    1984-05-01

    A prospective, single-blinded study was done to determine the ability of serial 99mtechnetium-diethylenetriaminepentaacetic acid scans to diagnose renal allograft rejection. Among 28 transplant recipients 111 renal scans were obtained 1 day postoperatively and every 3 to 4 days thereafter for 3 weeks in all patients retaining an allograft. Computer-generated time-activity blood flow curves were analyzed semiquantitatively for the 1) interval between curve peaks of the allograft and iliac artery, 2) renal transit time and 3) renal washout of radionuclide. Excretory function was assessed by degree and interval to appearance of radionuclide in the calices and bladder. Deterioration of renal blood flow and excretion compared to the initial scan was considered rejection. Of 52 scans performed during clinical rejection 47 (90.4 per cent) were interpreted as showing rejection (sensitivity). Of 53 scans interpreted as showing rejection 47 (88.7 per cent) were positive for clinical rejection. The remaining 6 patients (initial false positive results) suffered clinical rejection within 24 to 72 hours. We conclude that 99mtechnetium-diethylenetriaminepentaacetic acid renal scans are useful in the differential diagnosis of renal allograft dysfunction.

  9. Crystal growth of aragonite and calcite in presence of citric acid, DTPA, EDTA and pyromellitic acid.

    PubMed

    Westin, K-J; Rasmuson, A C

    2005-02-15

    The influence of four calcium complexing substances, i.e., citric acid (CIT), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA) and pyromellitic acid (PMA), on the crystal growth rate of the calcium carbonate polymorphs aragonite and calcite has been studied. Using a seeded constant supersaturation method supersaturation was maintained at 4 by keeping a constant pH of 8.5 through addition of sodium carbonate and calcium chloride solutions. The unique composition of each solution was calculated using chemical speciation. The growth rate was interpreted in terms of an overall growth rate. For both calcite and aragonite, the crystal growth rate is significantly reduced in the presence of the calcium complexing substances. The growth retarding effect depends on both the concentration and the polymorph. The relative crystal growth rate was correlated to the total complexing agent concentration using a Langmuir adsorption approach. Aragonite appeared fully covered for lower total concentrations than calcite. Furthermore, CIT very efficiently blocked aragonite growth contrary to what was observed for calcite. This is thought to be related to certain distinct features of the dominant aragonite crystal faces compared to the dominant calcite faces.

  10. Synthesis of diethylenetriaminepentaacetic acid conjugated inulin and utility for cellular uptake of liposomes

    SciTech Connect

    Essien, H.; Lai, J.Y.; Hwang, K.J.

    1988-05-01

    The synthesis, binding of radioactive cations, liposomal encapsulation, and biodistribution of the oxidized-inulin reaction product with ethylenediamine and diethylenetriaminepentaacetic acid (4) are described. The four-step synthesis of the inulin derivative proceeded in a good overall yield of 72%. The complex of the inulin derivative with either /sup 67/Ga3+ or /sup 111/In3+ was stable in vivo and did not readily distribute into tissues, being excreted primarily in urine after intravenous administration to mice. The liposome-entrapped inulin derivative can be loaded with radioactive heavy metal cations by mobile ionophores in high radiochemical yields of 80-91%. Following the intravenous administration of the liposomal encapsulation of the indium-111-labeled inulin derivative, the entrapped compound had a biodistribution characteristic of liposomes and allowed an estimation of the extent of the intracellular uptake of liposomes. The ability of the inulin derivative to chelate many different types of metals will allow the use of this probe for studying subtle differences in tissue distribution resulting from different drug targeting or delivery protocols in the same animal by multiple labeling techniques. Moreover, the chelate-conjugated inulin permits studies of the applications of drug delivery systems in primates or human subjects by noninvasive techniques such as gamma-scintigraphic or nuclear magnetic resonance imaging methods.

  11. Adsorption of chromium from aqueous solutions using crosslinked chitosan-diethylenetriaminepentaacetic acid.

    PubMed

    Bhatt, Ronak; Sreedhar, B; Padmaja, P

    2015-03-01

    Chitosan (CH) and its derivatives have been the focus of attention for researchers as potential adsorbents for heavy metal removal. The adsorption potential of chitosan cross-linked with diethylenetriaminepentaacetic acid (CD) for Cr6+ was investigated. CD was characterized by FTIR, XRD, TGA, XPS and ESR techniques. Batch experiments were conducted to optimize the parameters affecting the adsorption of chromium. The optimum pH was found to be 3 and the adsorption process was found to be exothermic. Adsorption isotherms were determined and the maximum adsorption capacity of CD for chromium was found to be 192.3 mg/g which was higher than the adsorption capacity of the adsorbents reported in literature. The thermodynamic parameters, such as Gibbs free energy, changes in enthalpy and changes in entropy change were also evaluated. XPS and ESR studies revealed that Cr6+ adsorbed onto CD was reduced to Cr3+. The efficacy of CD for removal of Cr6+ from chrome plating effluent was demonstrated.

  12. DFT investigation of Ni(II) adsorption onto MA-DTPA/PVDF chelating membrane in the presence of coexistent cations and organic acids.

    PubMed

    Song, Laizhou; Zhao, Xiaodan; Fu, Jie; Wang, Xiuli; Sheng, Yiping; Liu, Xiaowei

    2012-01-15

    Melamine-diethylenetriaminepentaacetic acid/polyvinylidene fluoride (MA-DTPA/PVDF) chelating membrane bearing polyaminecarboxylate groups was used to remove Ni(II) from nickel plating effluents. Adsorption experiments were conducted to study the adsorption of the membrane towards Ni(II) in Ni(II)-Ca(II), Ni(II)-NH(4)(+), Ni(II)-Fe(III) binary systems, and Ni(II)-lactic acid, Ni(II)-succinic acid and Ni(II)-citric acid complex systems. For the ternary nickel plating processes, the effects of 3d transition metals including Fe(II), Co(II), Cu(II) and Zn(II) on Ni(II) adsorption were evaluated. The influences of the aforementioned coexistent cations and organic acids were elucidated by the continuum solvation model (COSMO)-corrected density functional theory (DFT) method. Geometries and complexation energies were analyzed for metal-MA-DTPA and Ni(II)-organic acid complexes. DFT results accord with the experimental data, indicating that DFT is helpful to evaluate the complexation between the membrane and metal cations. The coexistent Ca(II) tends to form more stable complex with MA-DTPA ligand than NH(4)(+) and Fe(III), and can interfere with the formation of Ni(II)-MA-DTPA complex. The complexing sequence of 3d metals with MA-DTPA ligand is Zn(II)acid complexes follow the order of lactic acidacidacid, but cannot be comparable to that of Ni(II)-MA-DTPA complex.

  13. Thermodynamic study of the complexation of protactinium(V) with diethylenetriaminepentaacetic acid.

    PubMed

    Mendes, Mickaël; Leguay, Sébastien; Le Naour, Claire; Hamadi, Séna; Roques, Jérôme; Moisy, Philippe; Guillaumont, Dominique; Topin, Sylvain; Aupiais, Jean; Den Auwer, Christophe; Hennig, Christoph

    2013-07-01

    The complex formation of protactinium(V) with DTPA was studied at different temperatures (25-50 °C) and ionic strengths (0.1-1 M) with the element at tracer scale. Irrespective of the temperature and ionic strength studied, only one neutral complex with (1:1) stoichiometry was identified from solvent extraction and capillary electrophoresis coupled to ICP-MS (CE-ICP-MS) experiments. Density Functional Theory (DFT) calculations revealed that two complexes can be considered: Pa(DTPA) and PaO(H2DTPA). The associated formation constants were determined from solvent extraction data at different ionic strengths and temperatures and then extrapolated to zero ionic strength by SIT methodology. These constants are valid, regardless of complex form, Pa(DTPA) or PaO(H2DTPA). The standard thermodynamic data determined with these extrapolated constants revealed a very stable complex formed energetically by an endothermic contribution which is counter balanced by a strong entropic contribution. Both, the positive enthalpy and entropy energy terms suggest the formation of an inner sphere complex.

  14. Technetium-99m diethylenetriaminepentaacetic acid radioaerosol scintigraphy in organophosphate induced pulmonary toxicity: experimental study.

    PubMed

    Yavuz, Yucel; Kaya, Eser; Yurumez, Yusuf; Sahin, Onder; Bas, Orhan; Fidan, Huseyin; Sezer, Murat

    2008-09-01

    The aim of this experimental study was to investigate pathological signs of lung damages caused by acute organophosphate (OP) poisoning by using Tc-99m DTPA radioaerosol scintigraphy and histopathological investigation. Fourteen rabbits were divided into two equal groups (n = 7). Group 1 (control group) received normal saline (same volume of fenthion, 2 ml/kg) via orogastric tube. Group 2 (OP toxicity group) received 150 mg/kg of fenthion (diluted fenthion, 2 ml/kg) via orogastric tube. Six hours later, Tc-99m-DTPA aerosol inhalation lung scintigraphy was performed in both groups. Then all rabbits were anesthetized with ketamine hydrochloride (35 mg/kg, i.p.) and xysilazine (5 mg/kg, i.p.), and sacrificed by intracardiac blood discharge. The lungs were then removed. There was a significant difference in T1/2 values of Tc-99m DTPA clearance between control group and OP toxicity group (p = 0.04). Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar, and bronchial lumen, alveolar destruction, emphysematous changes, and bronchoalveolar hemorrhage scores were significantly higher in the rabbits exposed to OP compared with the control group (p < 0.05). This study showed that OP toxicity caused a decrease in the alveolar clearance. Tc-99m DTPA radioaerosol inhalation lung scintigraphy was found to be a sensitive determination of acute lung damage in OP poisoning.

  15. Gadoxate disodium: gadolinium EOB DTPA, gadoxetic acid, Gd-EOB-DTPA.

    PubMed

    2004-01-01

    Gadoxate disodium [gadolinium EOB DTPA, Gd-EOB-DTPA, gadoxetic acid, Eovist injection, Primovist] is a hydrophilic paramagnetic contrast agent being developed by Schering AG for hepatobiliary magnetic resonance imaging. In April 2004, gadoxate disodium (Primovist) was approved in Sweden, the reference member state for the EU registration. Following the Swedish approval, Schering will initiate a mutual recognition procedure for the EU with approvals expected in most countries during 2004. Gadoxate disodium is in phase III clinical trials in the US and has completed phase III studies in Japan. Submissions for approval in Japan and other Asian countries are planned for 2004. Schering AG plans to launch Eovist in Japan in 2005. Schering AG acquired a worldwide, royalty-bearing licence to EPIX Medical's patents covering liver-enhancing agents such as Eovist injection. These included a European patent (222886) and the US patents (4,899,755 and 4,888,008) that EPIX Medical exclusively licensed from the Massachusetts General Hospital (MGH). The MGH patents, a part of EPIX's extensive intellectual property, also covered albumin-targeted agents such as MS 325 (AngioMARK). Schering AG formally withdrew from the opposition proceedings against EPIX's EU patent 222886 following its acquisition of EPIX's intellectual property. These EU and US patents were also non-exclusively licensed by EPIX Medical to Bracco in September 2001. Apart from covering Eovist (Schering AG), the EU patent also covered gadobenate dimeglumine (MultiHance Bracco). Following the licensing agreement, Bracco withdrew its opposition to the patents in Europe and Japan, and both EPIX Medical and Bracco settled their European patent dispute. In its 2002 Annual Report, Schering predicted that Eovist has the potential to reach peak sales of euro50 million, three years after launch--at the time, launch in Europe was anticipated in 2004, followed by launch in Japan in 2005. This is down from earlier predictions

  16. Spectrophotometric determination and removal of unchelated europium ions from solutions containing Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates.

    PubMed

    Elshan, N G R Dayan; Patek, Renata; Vagner, Josef; Mash, Eugene A

    2014-11-01

    Europium chelates conjugated with peptide ligands are routinely used as probes for conducting in vitro binding experiments. The presence of unchelated Eu ions in these formulations gives high background luminescence and can lead to poor results in binding assays. In our experience, the reported methods for purification of these probes do not achieve adequate removal of unchelated metal ions in a reliable manner. In this work, a xylenol orange-based assay for the quantification of unchelated metal ions was streamlined and used to determine levels of metal ion contamination as well as the success of metal ion removal on attempted purification. We compared the use of Empore chelating disks and Chelex 100 resin for the selective removal of unchelated Eu ions from several Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates. Both purification methods gave complete and selective removal of the contaminant metal ions. However, Empore chelating disks were found to give much higher recoveries of the probes under the conditions used. Related to the issue of probe recovery, we also describe a significantly more efficient method for the synthesis of one such probe using Rink amide AM resin in place of Tentagel S resin.

  17. Decorporation of plutonium by pulmonary administration of Ca-DTPA dry powder: a study in rat after lung contamination with different plutonium forms.

    PubMed

    Sérandour, A L; Tsapis, N; Gervelas, C; Grillon, G; Fréchou, M; Deverre, J R; Bénech, H; Fattal, E; Fritsch, P; Poncy, J L

    2007-01-01

    This study evaluates the decorporation efficacy of a pulmonary administration of a new Ca-DTPA (diethylenetriaminepentaacetic acid) dry powder (18 micromol kg(-1) of body mass) after pulmonary contamination of rats with different Pu compounds. After inhalation of PuO2, a delayed intratracheal administration of DTPA cannot reduce significantly the retention of Pu in the lungs but limits its transfer in liver and skeleton. After pulmonary contamination by Pu nitrate, early insufflation of the DTPA powder appears twice as more efficient than an i.v injection of DTPA (30 micromol kg(-1)) to reduce Pu retention in the lungs and is as effective as i.v. injection to limit the extrapulmonary deposit. In contrast, a delayed administration of DTPA cannot reduce the lung or extrapulmonary retention. In conclusion, the improvement of aerodynamic properties of DTPA powder leads to an increase of DTPA amount deposited in the lungs and enhances the body decorporation.

  18. Design, synthesis and biological evaluation of negatively charged ¹¹¹In-DTPA-octreotide derivatives.

    PubMed

    Oshima, Nobuhiro; Akizawa, Hiromichi; Zhao, Songji; Zhao, Yan; Nishijima, Ken-ichi; Kitamura, Yoji; Arano, Yasushi; Kuge, Yuji; Ohkura, Kazue

    2014-02-15

    Our previous studies indicated that (111)In-diethylenetriaminepentaacetic acid ((111)In-DTPA)-octreotide derivatives with an additional negative charge by replacing N-terminal d-phenylalanine (d-Phe) with an acidic amino acid such as l-aspartic acid (Asp) or its derivative exhibited low renal radioactivity levels when compared with (111)In-DTPA-D-Phe(1)-octreotide. On the basis of the findings, we designed, synthesized and evaluated two Asp-modified (111)In-DTPA-conjugated octreotide derivatives, (111)In-DTPA-Asp(1)-octreotide and (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide. While (111)In-DTPA-Asp(1)-octreotide showed negligible AR42J cell uptake, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited AR42J cell uptake similar to that of (111)In-DTPA-D-Phe(1)-octreotide. When administered to AR42J tumor-bearing mice, (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited renal radioactivity levels significantly lower than did (111)In-DTPA-D-Phe(1)-octreotide at 1 and 3 h post-injection. No significant differences were observed in tumor accumulation between (111)In-DTPA-Asp(0)-D-Phe(1)-octreotide and (111)In-DTPA-D-Phe(1)-octreotide after 1 and 3h injection. The findings in this study suggested that an interposition of an Asp at an appropriate position in (111)In-DTPA-D-Phe(1)-octreotide would constitute a useful strategy to develop (111)In-DTPA-D-Phe(1)-octreotide derivatives of low renal radioactivity levels while preserving tumor accumulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Evaluation of the therapeutic effect of percutaneous nephroureterolithotomy by Tc-99m diethylenetiaminepentaacetic acid (DTPA) renal scintigraphy--alteration of the renal fraction of blood flow, split-GFR, and renal mean transit time.

    PubMed

    Ishibashi, M; Morita, S; Rabito, C A; Umezaki, N; Matsuoka, K; Noda, S; Eto, K; Ohtake, H

    1990-01-01

    To evaluate the therapeutic effects of percutaneous nephroureterolithotomy, the renal function of eleven patients with renal calculi was studied, pre- and post-intervention. Renal function was determined, by renal scintigraphy with the renal agent, Tc-99m diethylenetriaminepentaacetic acid (DTPA). In each renal scintigram the renogram curve was analyzed and the following were determined by deconvolution analysis; the renal fraction of blood flow (RFBF), DTPA-glomerular filtration ratio (GFR), and the renal mean transit time (MTT). The successful results in percutaneous nephroureterolithotomy (PNL) was proven using the radionuclide technique in most cases. From these results it can be concluded that renal scintigraphy is an effective procedure to evaluate the effect of PNL for treating renal calculi and secondary hydronephrosis.

  20. Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent

    SciTech Connect

    Weinmann, H.J.; Brasch, R.C.; Press, W.R.; Wesbey, G.E.

    1984-03-01

    Chelation of the rare-earth element gadolinium (Gd) with diethylenetriaminepentaacetic acid (DTPA) results in a strongly paramagnetic, stable complex that is well tolerated in animals. The strongly paramagnetic gadolinium complex reduces hydrogen-proton relaxation times even in low concentrations (less than 0.01 mmol/L). The pharmacokinetic behavior of intravenously delivered Gd-DTPA is similar to the well known iodinated contrast agents used in urography and angiography; excretion is predominately through the kidneys with greater than 90% recovery in 24 hr. The intravenous LD/sub 50/ of the meglumine salt of Gd-DTPA is 10 mmol/kg for the rat; in vivo there is no evidence of dissociation of the gadolinium ion from the DTPA ligand. The combination of strong proton relaxation, in-vivo stability, rapid urinary excretion, and high tolerance favors the further development and the potential clinical application of gadolinium-DTPA as a contrast enhancer in magnetic resonance imaging.

  1. Gd-DTPA-loaded polymer-metal complex micelles with high relaxivity for MR cancer imaging.

    PubMed

    Mi, Peng; Cabral, Horacio; Kokuryo, Daisuke; Rafi, Mohammad; Terada, Yasuko; Aoki, Ichio; Saga, Tsuneo; Takehiko, Ishii; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2013-01-01

    Nanodevices for magnetic resonance imaging of cancer were self-assembled to core-shell micellar structures by metal complex formation of K(2)PtCl(6) with diethylenetriaminepentaacetic acid gadolinium (III) dihydrogen (Gd-DTPA), a T(1)-contrast agent, and poly(ethylene glycol)-b-poly{N-[N'-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-PAsp(DET)) copolymer in aqueous solution. Gd-DTPA-loaded polymeric micelles (Gd-DTPA/m) showed a hydrodynamic diameter of 45 nm and a core size of 22 nm. Confining Gd-DTPA inside the core of the micelles increased the relaxivity of Gd-DTPA more than 13 times (48 mM(-1) s(-1)). In physiological conditions Gd-DTPA/m sustainedly released Gd-DTPA, while the Pt(IV) complexes remain bound to the polymer. Gd-DTPA/m extended the circulation time in plasma and augmented the tumor accumulation of Gd-DTPA leading to successful contrast enhancement of solid tumors. μ-Synchrotron radiation-X-ray fluorescence results confirmed that Gd-DTPA was delivered to the tumor site by the micelles. Our study provides a facile strategy for incorporating contrast agents, dyes and bioactive molecules into nanodevices for developing safe and efficient drug carriers for clinical application.

  2. Indium-111 labeled monoclonal antibodies (Ab): The effect of DTPA conjugation on the Ab activity and tissue distribution

    SciTech Connect

    Sakahara, H.; Endo, K.; Nakashima, T.; Ohta, H.; Okada, K.; Yoshida, O.; Ohmomo, Y.; Horiuchi, K.; Yokoyama, A.; Torizuka, K.

    1984-01-01

    Monoclonal antibodies (Ab) to human ..cap alpha..-fetoprotein (AFP) were conjugated with diethylenetriaminepentaacetic acid (DTPA) using cyclic DTPA anhydride and the obtained conjugates, DTPA-Ab, were labeled with In-111. The effect of DTPA conjugation on the affinity constant and the maximum binding capacity of Ab was evaluated by radioimmunoassay and Scatchard plot analysis and In-111 labeled DTPA-Ab were used for the radioimmunodetection of tumor. Ab containing 1.0 DTPA molecule per Ab showed almost full retention of both the affinity constant and the maximum binding capacity. Then, 40 ..mu..Ci of In-111 labeled DTPA-Ab were injected intravenously to nude mice bearing AFP-producing human testicular tumor and the resulted were compared with I-131 labeled Ab. Scintigraphy clearly revealed transplanted tumor. Localization of In-111 labeled DTPA-Ab was significantly higher than I-131 labeled Ab. Tumor to blood ratio obtained at 4 days after injection was 2.59 with In-111 labeled DTPA-Ab compared to 0.99 with I-131 labeled Ab. When more than 1.9 DTPA molecules were incorporated per Ab, the maximum binding capacity decreased, although the affinity constant was less affected. These In-111 labeled DTPA-Ab caused significantly higher liver accumulation. These results indicate that In-111 labeled DTPA-Ab at a cojugated DTPA to Ab molar ratio of 1.0 may be superior to I-131 labeled Ab for tumor imaging, but the maximum binding capacity and tissue distribution of In-111 labeled DTPA-AB are greatly dependent upon the number of DTPA molecules incorporated per Ab molecule.

  3. Species-dependent effective concentration of DTPA in plasma for chelation of 241Am.

    PubMed

    Sueda, Katsuhiko; Sadgrove, Matthew P; Jay, Michael; Di Pasqua, Anthony J

    2013-08-01

    Diethylenetriaminepentaacetic acid (DTPA) is a chelating agent that is used to facilitate the elimination of radionuclides such as americium from contaminated individuals. Its primary site of action is in the blood, where it competes with various biological ligands, including transferrin and albumin, for the binding of radioactive metals. To evaluate the chelation potential of DTPA under these conditions, the competitive binding of Am between DTPA and plasma proteins was studied in rat, beagle, and human plasma in vitro. Following incubation of DTPA and Am in plasma, the Am-bound ligands were fractionated by ultrafiltration and ion-exchange chromatography, and each fraction was assayed for Am content by gamma scintillation counting. Dose response curves of DTPA for Am binding were established, and these models were used to calculate the 90% maximal effective concentration, or EC90, of DTPA in each plasma system. The EC90 were determined to be 31.4, 15.9, and 10.0 μM in rat, beagle, and human plasma, respectively. These values correspond to plasma concentrations of DTPA that maximize Am chelation while minimizing excess DTPA. Based on the pharmacokinetic profile of DTPA in humans, after a standard 30 μmol kg intravenous bolus injection, the plasma concentration of DTPA remains above EC90 for approximately 5.6 h. Likewise, the effective duration of DTPA in rat and beagle were determined to be 0.67 and 1.7 h, respectively. These results suggest that species differences must be considered when translating DTPA efficacy data from animals to humans and offer further insights into improving the current DTPA treatment regimen.

  4. Species-dependent effective concentration of DTPA in plasma for chelation of 241Am

    PubMed Central

    Sueda, Katsuhiko; Sadgrove, Matthew P.; Jay, Michael; Di Pasqua, Anthony J.

    2013-01-01

    Diethylenetriaminepentaacetic acid (DTPA) is a chelating agent that is used to facilitate the elimination of radionuclides, such as americium, from contaminated individuals. Its primary site of action is in the blood, where it competes with various biological ligands, including transferrin and albumin, for the binding of radioactive metals. To evaluate the chelation potential of DTPA under these conditions, the competitive binding of 241Am between DTPA and plasma proteins was studied in rat, beagle and human plasma in vitro. Following incubation of DTPA and 241Am in plasma, the 241Am-bound ligands were fractionated by ultrafiltration and ion-exchange chromatography, and each fraction was assayed for 241Am content by gamma scintillation counting. Dose-response curves of DTPA for 241Am binding were established, and these models were used to calculate the 90% maximal effective concentration, or EC90, of DTPA in each plasma system. The EC90 were determined to be 31.4, 15.9 and 10.0 μM in rat, beagle and human plasma, respectively. These values correspond to plasma concentrations of DTPA that maximize 241Am chelation while minimizing excess DTPA. Based on the pharmacokinetic profile of DTPA in humans, after a standard 30 μmol kg−1 intravenous bolus injection, the plasma concentration of DTPA remains above EC90 for approximately 5.6 h. Likewise, the effective duration of DTPA in rat and beagle were determined to be 0.67 and 1.7 h, respectively. These results suggest that species differences must be considered when translating DTPA efficacy data from animals to humans and offer further insights into improving the current DTPA treatment regimen. PMID:23799506

  5. 99mTc-DTPA-amino acids conjugate as specific SPECT pharmaceuticals for tumor imaging.

    PubMed

    Sinha, Deepa; Shukla, Gauri; Tiwari, Anjani K; Chaturvedi, Shubhra; Chuttani, Krishna; Chandra, Harish; Mishra, Anil K

    2009-08-01

    (99m)Tc-Diethylene triamine pentaacetic acid-bis (amide) conjugates have been synthesized and evaluated as a potential radiopharmaceutical for tumor imaging. The compounds were synthesized by the condensation reaction of DTPA bis(anhydride) with different l-amino acids (methyl tryptophan, and 5-hydroxy tryptophan) and were characterized on the basis of IR, NMR, and Mass spectroscopy. (99m)Tc-labeled compounds were found stable for about 24 h under physiological conditions with more than 95% radiolabeling yield. Blood kinetic studies of all these complexes showed a bi-exponential pattern as well as quick wash out from the blood circulation. The biological t(1/2)(F) and t(1/2)(S) were found to be 20 +/- 0.001 min for DTPA-(Me-Trp)(2) and 18 +/- 0.001 min for DTPA-(5HT)(2) and t(1/2) (slow) 5 h 45 min +/- 0.001, 5 h 30 +/- 0.001 min for DTPA-(Me-Trp)(2), and DTPA-(5HT)(2), respectively. Imaging and biodistribution studies were performed in mice bearing Ehrlich ascites tumor (EAT) tumors in right thigh. Radioconjugate derived from l-5-hydroxytryptophan exhibited remarkable localization at tumor site; whereas radiotracer derived from l-methyl tryptophan shows relatively less accumulation at the tumor site. Tumor-to-muscles ratios were 5.07 +/- 0.001, and 4.2 +/- 0.001 at 1 and 4 h for (99m)Tc-DTPA-(Me trp)(2) and 4.97 +/- 0.001 and 5.8 +/- 0.001 at 1 and 4 h after postinjection for (99m)Tc-DTPA-(5HT)(2), respectively. The preliminary results with these amino acid based ligands are encouraging to carrying out further in vivo experiments for targeted tumor imaging.

  6. Decorporation and therapeutic efficacy of liposomal-DTPA against thorium-induced toxicity in the Wistar rat.

    PubMed

    Kumar, Amit; Sharma, Pragya; Ali, Manjoor; Pandey, Badri Narain; Mishra, Kaushala Prasad

    2012-03-01

    This study examined the effect of liposomal encapsulation of (99m)Tc-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium ((232)Th)-induced liver toxicity and its accumulation in rat animal model. (99m)Tc-DTPA was encapsulated in neutral (dipalmitoylphosphatidylcholine:cholesterol) and positively (dipalmitoylphosphatidylcholine:cholesterol:stearylamine) charged liposomes using thin film hydration method. Comparative efficacy of liposomal and free DTPA (11.2 mg/kg) was examined in terms of its effect on (232)Th accumulation and subsequent toxicity in the liver and blood of rat administered with (232)Th-nitrate (600 μg/kg). Organ distribution of free or liposomal (99m)Tc-DTPA was determined by solid scintillation counting and (232)Th accumulation by Inductively Coupled Plasma-Atomic Emission Spectroscopy. Neutral liposomes encapsulated with (99m)Tc-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal- and free- (99m)Tc-DTPA. Administration of (232)Th-nitrate to rat significantly increased the levels of liver toxicity markers and of oxidative injury, which were found to be restored more significantly by neutral liposomal-DTPA than free-DTPA. The accumulation of (232)Th in liver and blood of contaminated mice was found to be decreased more significantly by neutral liposomal-DTPA than by free-DTPA. Decorporation and consequent mitigation of (232)Th induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent.

  7. Treatment of human contamination with plutonium and americium: would orally administered Ca- or Zn-DTPA be effective?

    PubMed

    Taylor, David M; Hodgson, Susan A; Stradling, Neil

    2007-01-01

    Accidental or deliberate dispersion of plutonium (Pu) and americium (Am) into the public environment could contaminate large numbers of people by inhalation. If measures to reduce the internal dose are considered appropriate, oral administration of either calcium (Ca) or zinc (Zn) diethylenetriaminepenta-acetic acid (DTPA) would be the simplest treatment. Published experimental data from rats on the effects of oral DTPA on the retention of inhaled Pu and Am show that: (1) orally administered Zn-DTPA is as effective as repeated intravenous injection for the decorporation of Pu and Am inhaled as nitrates, although higher dosages are required; (2) oral Zn-DTPA appears to be an effective treatment for Am dioxide but not Pu dioxide; (3) maximum decorporation of Pu, by oral or intravenous administration, requires a large molar excess of Zn-DTPA over Pu (>1 x 10(6)); (4) neither oral nor injected Zn-DTPA are likely to be effective for Pu oxides, nor when Pu and Am nitrates are mixed with other dusts. It is concluded that oral administration of a simple aqueous solution of Zn-DTPA could be an important treatment in accident or emergency scenarios after intake of pure chemical forms of Pu and Am, which are highly or moderately soluble in biological fluids. However, more research is needed on the efficacy of treatment when these forms are mixed with other materials. Importantly, studies designed to increase the efficiency of uptake of DTPA from the gastrointestinal tract could appreciably reduce the dosage.

  8. Concise site-specific synthesis of DTPA-peptide conjugates: application to imaging probes for the chemokine receptor CXCR4.

    PubMed

    Masuda, Ryo; Oishi, Shinya; Ohno, Hiroaki; Kimura, Hiroyuki; Saji, Hideo; Fujii, Nobutaka

    2011-05-15

    Diethylenetriaminepentaacetic acid (DTPA) is a useful chelating agent for radionuclides such as (68)Ga, (99m)Tc and (111)In, which are applicable to nuclear medicine imaging. In this study, we established a facile synthetic protocol for the production of mono-DTPA-conjugated peptide probes. A novel monoreactive DTPA precursor reagent was synthesized in two steps using the chemistry of the o-nitrobenzenesulfonyl (Ns) protecting group, and under mild conditions this DTPA precursor was incorporated onto an N(ε)-bromoacetylated Lys of a protected peptide resin. The site-specific DTPA conjugation was facilitated by using a highly acid-labile 4-methyltrityl (Mtt) protecting group for the target site of the bioactive peptide during the solid-phase synthesis. A combination of both techniques yielded peptides with disulfide bonds, such as octreotide and polyphemusin II-derived CXCR4 antagonists. DTPA-peptide conjugates were purified in a single step following cleavage from the resin and disulfide bond formation. This site-specific on-resin construction strategy was used for the design and synthesis of a novel In-DTPA-labeled CXCR4 antagonist, which exhibited highly potent inhibitory activity against SDF-1-CXCR4 binding. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Decorporation of Pu/Am Actinides by Chelation Therapy: New Arguments in Favor of an Intracellular Component of DTPA Action.

    PubMed

    Grémy, Olivier; Laurent, David; Coudert, Sylvie; Griffiths, Nina M; Miccoli, Laurent

    2016-06-01

    Diethylenetriaminepentaacetic acid (DTPA) is currently still the only known chelating drug that can be used for decorporation of internalized plutonium (Pu) and americium (Am). It is generally assumed that chelation occurs only in biological fluids, thus preventing Pu/Am deposition in target tissues. We postulate that actinide chelation may also occur inside cells by a mechanism called "intracellular chelation". To test this hypothesis, rats were given DTPA either prior to (termed "prophylactic" treatment) or belatedly after (termed "delayed" treatment) Pu/Am injection. DTPA decorporation efficacy was systematically tested for both plutonium and americium. Both prophylactic and delayed DTPA elicited marked decreases in liver Pu/Am. These results can be explained by chelation within subcellular compartments where DTPA efficacy increased as a function of a favorable intracellular DTPA-to-actinide molar ratio. The efficacy of intracellular chelation of liver actinides decreased with the delay of treatment. This is probably explained by progressive actinide binding to the high-affinity ligand ferritin followed by migration to lysosomes. Intracellular chelation was reduced as the gap between prophylactic treatment and contamination increased. This may be explained by the reduction of the intracellular DTPA pool, which declined exponentially with time. Skeletal Pu/Am was also reduced by prophylactic and delayed DTPA treatments. This decorporation of bone actinides may mainly result from extracellular chelation on bone surfaces. This work provides converging evidence for the involvement of an intracellular component of DTPA action in the decorporation process. These results may help to improve the interpretation of biological data from DTPA-treated contamination cases and could be useful to model DTPA therapy regimens.

  10. Hyaluronic Acid-Chitosan Nanoparticles to Deliver Gd-DTPA for MR Cancer Imaging

    PubMed Central

    Zhang, Li; Liu, Tingxian; Xiao, Yanan; Yu, Dexin; Zhang, Na

    2015-01-01

    Molecular imaging is essential to increase the sensitivity and selectivity of cancer diagnosis especially at the early stage of tumors. Recently, polyionic nanocomplexes (PICs), which are composed of polyanions and opposite polycations, have been demonstrated to be a promising strategy for biomedical applications. In this work, chitosan-hyaluronic acid nanoparticles (GCHN) were developed to deliver Gd-DTPA as MRI contrast agents for tumor diagnosis. The Gd-labeled conjugates (CS-DTPA-Gd) were successfully synthesized by carbodiimide reaction, and then GCHN were prepared by ionic gelation using the obtained CS-DTPA-Gd and hyaluronic acid. The morphology of GCHN was spherical or ellipsoidal, which is observed by transmission electronic microscopy (TEM). The mean particle size and zeta potential of GCHN were 213.8 ± 2.6 nm and 19.92 ± 1.69 mV, respectively. The significant enhancement of signal intensity induced by GCHN was observed both in vitro and in vivo. Also, compared with Magnevist, GCHN was witnessed for a prolonged imaging time in the B16 tumor-bearing mice model. Furthermore, GCHN were verified as below toxic both in vitro and in vivo. These results indicated that GCHN could potentially be an alternative to current MRI contrast agents for tumor diagnosis.

  11. Simple Fabrication of Gd(III)-DTPA-Nanodiamond Particles by Chemical Modification for Use as Magnetic Resonance Imaging (MRI) Contrast Agent

    NASA Astrophysics Data System (ADS)

    Nakamura, Takako; Ohana, Tsuguyori; Yabuno, Hajime; Kasai, Rumiko; Suzuki, Tetsuya; Hasebe, Terumitsu

    2013-01-01

    We have developed a simple and useful process for fabricating nanodiamond (ND) particles modified with an organogadolinium moiety by chemical modification for their use as a magnetic resonance imaging (MRI) contrast agent. The introduction of the organogadolinium moiety on the surface of the ND particles was performed by the condensation of ND and diethylenetriaminepentaacetic acid (DTPA) followed by treatment with GdCl3. The modified surfaces were evaluated by X-ray photoelectron spectroscopy, diffuse reflectance Fourier transform infrared spectroscopy, mass spectroscopy, and inductively coupled plasma atomic emission spectroscopy analyses. MRI experiments on the Gd-DTPA-ND particles indicated their high signal intensity on T1-weighted images.

  12. Capture of Co(II) from its aqueous EDTA-chelate by DTPA-modified silica gel and chitosan.

    PubMed

    Repo, Eveliina; Malinen, Leena; Koivula, Risto; Harjula, Risto; Sillanpää, Mika

    2011-03-15

    The adsorption of Co(II) by diethylenetriaminepentaacetic acid (DTPA)-modified silica gel and chitosan in the presence of EDTA and other interfering species was studied. Co(II) removal ranged from 93% to 96% from the solutions where Co(II) was totally chelated by EDTA. The amount of oxalate or Fe(II) did not affect the adsorption of Co(II) in the case of DTPA-chitosan. However, increasing the amount of oxalate enhanced the adsorption performance of DTPA-silica gel, probably due to the formation of new active sites on the silica gel surface. DTPA-chitosan was also effective in simulated decontamination solutions. For DTPA-silica gel, the rate of adsorption of free Co(II) was controlled by pore diffusion, but the rate of adsorption of Co(II)EDTA was controlled by the surface chelation reaction, which was attributed to the inhibited diffusion of Co(II)EDTA inside the silica gel mesopores. However, the macroporous structure of DTPA-chitosan enabled pore diffusion of both Co(II) and Co(II)EDTA. The equilibrium isotherms of DTPA-silica gel were best described by a BiLangmuir model, in which there are two different adsorption sites on the silica gel surface assigned to different speciations of DTPA. For DTPA-chitosan, the data fit best with a Sips model, which indicates system heterogeneity. Finally, measurements with capillary electrophoresis showed an increase in dissolved EDTA during adsorption, demonstrating the ability of DTPA-modified adsorbents to release Co(II) from its EDTA chelate. This promising result can provide a basis for applying the studied materials to the treatment of water effluents containing Co(II) chelated by EDTA by a simple one-step adsorption process. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Orally administered DTPA penta-ethyl ester for the decorporation of inhaled (241)Am.

    PubMed

    Sueda, Katsuhiko; Sadgrove, Matthew P; Huckle, James E; Leed, Marina G D; Weber, Waylon M; Doyle-Eisele, Melanie; Guilmette, Raymond A; Jay, Michael

    2014-05-01

    Diethylenetriaminepentaacetic acid (DTPA) is an effective decorporation agent to facilitate the elimination of radionuclides from the body, but its permeability-limited oral bioavailability limits its utility in mass-casualty emergencies. To overcome this limitation, a prodrug strategy using the penta-ethyl ester form of DTPA is under investigation. Pharmacokinetic and biodistribution studies were conducted in rats by orally administering [(14) C]DTPA penta-ethyl ester, and this prodrug and its hydrolysis products were analyzed as a single entity. Compared with a previous reporting of intravenously administered DTPA, the oral administration of this prodrug resulted in a sustained plasma concentration profile with higher plasma exposure and lower clearance. An assessment of the urine composition revealed that the bioactivation was extensive but incomplete, with no detectable levels of the penta- or tetra-ester forms. Tissue distribution at 12 h was limited, with approximately 73% of the administered dose being associated with the gastrointestinal tract. In the efficacy study, rats were exposed to aerosols of (241) Am nitrate before receiving a single oral treatment of the prodrug. The urinary excretion of (241) Am was found to be 19% higher than with the control. Consistent with prior reports of DTPA, the prodrug was most effective when the treatment delays were minimized. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Orally administered DTPA penta-ethyl ester for the decorporation of inhaled 241Am

    PubMed Central

    Sueda, Katsuhiko; Sadgrove, Matthew P.; Huckle, James E.; Leed, Marina G. D.; Weber, Waylon M.; Doyle-Eisele, Melanie; Guilmette, Raymond A.; Jay, Michael

    2014-01-01

    Diethylenetriaminepentaacetic acid (DTPA) is an effective decorporation agent to facilitate the elimination of radionuclides from the body, but its permeability-limited oral bioavailability limits its utility in mass-casualty emergencies. To overcome this limitation, a prodrug strategy using the penta-ethyl ester form of DTPA is under investigation. Pharmacokinetic and biodistribution studies were conducted in rats by orally administering [14C]DTPA penta-ethyl ester, and this prodrug and its hydrolysis products were analyzed as a single entity. Compared to a previous reporting of intravenously administered DTPA, the oral administration of this prodrug resulted in a sustained plasma concentration profile with higher plasma exposure and lower clearance. An assessment of the urine composition revealed that the bioactivation was extensive but incomplete, with no detectable levels of the penta- or tetra-ester forms. Tissue distribution at 12 h was limited, with approximately 73% of the administered dose being associated with the gastrointestinal tract. In the efficacy study, rats were exposed to aerosols of 241Am nitrate before receiving a single oral treatment of the prodrug. The urinary excretion of 241Am was found to be 19% higher than with the control. Consistent with prior reports of DTPA, the prodrug was most effective when the treatment delays were minimized. PMID:24619514

  15. Linker effects on biological properties of 111In-labeled DTPA conjugates of a cyclic RGDfK dimer.

    PubMed

    Jia, Bing; Liu, Zhaofei; Shi, Jiyun; Yu, Zilin; Yang, Zhi; Zhao, Huiyun; He, Zhengjie; Liu, Shuang; Wang, Fan

    2008-01-01

    In this report, we present in vitro and in vivo evaluation of three 111 In-labeled DTPA conjugates of a cyclic RGDfK dimer: DTPA-Bn-SU016 (SU016 = E[c(RGDfK)] 2; DTPA-Bn = 2-( p-isothioureidobenzyl)diethylenetriaminepentaacetic acid), DTPA-Bn-E-SU016 ( E = glutamic acid) and DTPA-Bn-Cys-SU016 (Cys = cysteic acid). The integrin alpha vbeta 3 binding affinities of SU016, DTPA-Bn-SU016, DTPA-Bn-E-SU016, and DTPA-Bn-Cys-SU016 were determined to be 5.0 +/- 0.7 nM, 7.9 +/- 0.6 nM, 5.8 +/- 0.6 nM, and 6.9 +/- 0.9 nM, respectively, against 125 I-c(RGDyK) in binding to integrin alpha vbeta3, suggesting that E or Cys residue has little effect on the integrin alpha vbeta3 affinity of E[c(RGDfK)] 2. It was also found that the 111 In-labeling efficiency of DTPA-Bn-SU016 and DTPA-Bn-E-SU016 is 3-5 times better than that of DOTA analogues due to fast chelation kinetics and high-yield 111 In-labeling under mild conditions (e.g., room temperature). Biodistribution studies were performed using BALB/c nude mice bearing U87MG human glioma xenografts. 111 In-DTPA-Bn-SU016, 111 In-DTPA-Bn-E-SU016, and 111 In-DTPA-Bn-Cys-SU016 all displayed rapid blood clearance. Their tumor uptake was comparable between 0.5 and 4 h postinjection (p.i.) within experimental error. 111 In-DTPA-Bn-E-SU016 had a significantly lower ( p < 0.01) kidney uptake than 111 In-DTPA-Bn-SU016 and 111 In-DTPA-Bn-Cys-SU016. The liver uptake of 111 In-DTPA-Bn-SU016 was 1.69 +/- 0.18% ID/g at 24 h p.i., while the liver uptake values of 111 In-DTPA-Bn-E-SU016 and 111 In-DTPA-Bn-Cys-SU016 were 0.55 +/- 0.11% ID/g and 0.79 +/- 0.15% ID/g at 24 h p.i., respectively. Among the three 111 In radiotracers evaluated in this study, 111 In-DTPA-Bn-E-SU016 has the lowest liver and kidney uptake and the best tumor/liver and tumor/kidney ratios. Results from metabolism studies indicated that there is little metabolism (<10%) for three 111 In radiotracers at 1 h p.i. Imaging data showed that tumors can be clearly visualized at 4 h p

  16. Linker Effects on Biological Properties of 111In-Labeled DTPA Conjugates of a Cyclic RGDfK Dimer

    PubMed Central

    Jia, Bing; Liu, Zhaofei; Shi, Jiyun; Yu, Zilin; Yang, Zhi; Zhao, Huiyun; He, Zhengjie; Liu, Shuang; Wang, Fan

    2008-01-01

    In this report, we present in vitro and in vivo evaluation of three 111In-labeled DTPA conjugates of a cyclic RGDfK dimer: DTPA-Bn-SU016 (SU016 = E[c(RGDfK)]2; DTPA-Bn = 2-(p-isothiocyanobenzyl)diethylenetriaminepentaacetic acid), DTPA-Bn-E-SU016 (E = glutamic acid) and DTPA-Bn-Cys-SU016 (Cys = cysteic acid). The integrin αvβ3 binding affinities of SU016, DTPA-Bn-SU016, DTPA-Bn-E-SU016 and DTPA-Bn-Cys-SU016 were determined to be 5.0 ± 0.7 nM, 7.9 ± 0.6 nM, 5.8 ± 0.6 nM and 6.9 ± 0.9 nM, respectively, against 125I-c(RGDyK) in binding to integrin αvβ3, suggesting that E or Cys residue has little effect on the integrin αvβ3 affinity of E[c(RGDfK)]2. It was also found that the 111In-labeling efficiency of DTPA-Bn-SU016 and DTPA-Bn-E-SU016 is 3–5 times better than that of DOTA analogs due to fast chelation kinetics and high-yield 111In-labeling under mild conditions (e.g. room temperature). Biodistribution studies were performed using BALB/c nude mice bearing U87MG human glioma xenografts. 111In-DTPA-Bn-SU016, 111In-DTPA-Bn-E-SU016 and 111In-DTPA-Bn-Cys-SU016 all displayed a rapid blood clearance. Their tumor uptake was comparable between 0.5 h and 4 h postinjection (p.i.) within experimental error. 111In-DTPA-Bn-E-SU016 had a significantly lower (p < 0.01) kidney uptake than 111In-DTPA-Bn-SU016 and 111In-DTPA-Bn-Cys-SU016. The liver uptake of 111In-DTPA-Bn-SU016 was 1.69 ± 0.18 %ID/g at 24 h p.i. while the liver uptake of 111In-DTPA-Bn-E-SU016 and 111In-DTPA-Bn-Cys-SU016 was 0.55 ± 0.11 %ID/g and 0.79 ± 0.15 %ID/g at 24 h p.i., respectively. Among the three 111In radiotracers evaluated in this study, 111In-DTPA-Bn-E-SU016 has the lowest liver and kidney uptake and the best tumor/liver and tumor/kidney ratios. Results from metabolism studies indicated that there is little (<10%) metabolism for three 111In radiotracers at 1 h p.i. Imaging data showed that tumors can be clearly visualized at 4 h p.i. with good contrast in the tumor-bearing mice administered

  17. Design, synthesis and evaluation of a new Mn - Contrast agent for MR imaging of myocardium based on the DTPA-phenylpentadecanoic acid complex

    NASA Astrophysics Data System (ADS)

    Belyanin, Maxim L.; Stepanova, Elena V.; Valiev, Rashid R.; Filimonov, Victor D.; Usov, Vladimir Y.; Borodin, Oleg Y.; Ågren, Hans

    2016-11-01

    In the present paper we describe the first synthesis and evaluation of a novel Mn (II) complex (DTPA-PPDA Mn (II)) which contains a C-15 fatty acid moiety that has high affinity to the heart muscle. The complexation energy of DTPA-PPDA Mn (II) evaluated by quantum chemistry methodology indicates that it essentially exceeds the corresponding value for the known DTPA Mn (II) complex. Molecular docking revealed that the affinity of the designed complex to the heart-type transport protein H-FABP well exceeds that of lauric acid. Phantom experiments in low-field MRI the designed contrast agent provides MR imaging comparable to gadopentetic acid.

  18. [In vitro comparative study of plasma protein binding of 99mTc-DTPA used in renal scintigraphy].

    PubMed

    Chemlal, L; Makram, S; Zoubir, B; Cherrah, Y; Faouzi, M A

    2013-11-01

    The radiopharmaceutical (99m)Tc-DTPA (diethylene-triamine-pentaacetic acid) is a tracer widely used in renal scintigraphy to assess glomerular filtration rate. The estimation of protein binding is very important due to its impact on clinical parameters biodistribution since only the free fraction is filtered by the kidney. A number of laboratory techniques have been developed to study protein binding. Precipitation and ultrafiltration are the mostly used techniques in pharmacology for studies of the binding between proteins and small molecules. The aim of this work is to apply and compare those two analytical methods in (99m)Tc-DTPA protein binding determination in vitro before in vivo application. The results obtained by precipitation with trichloroacetic acid are not enough reproducible, while those obtained by ultrafiltration seem more consistent and reproducible.

  19. Receptor-binding, biodistribution, dosimetry, and micro-SPECT/CT imaging of 111In-[DTPA(1), Lys(3), Tyr(4)]-bombesin analog in human prostate tumor-bearing mice.

    PubMed

    Ho, Chung-Li; Chen, Liang-Cheng; Lee, Wan-Chi; Chiu, Shu-Pei; Hsu, Wei-Chuan; Wu, Yu-Hsien; Yeh, Chung-Hsin; Stabin, Michael G; Jan, Meei-Ling; Lin, Wuu-Jyh; Lee, Te-Wei; Chang, Chih-Hsien

    2009-08-01

    Gastrin-releasing peptide receptors (GRPRs) are overexpressed on a variety of human tumors, such as prostate, breast, and lung cancer. Bombesin (BN) is a 14-amino-acid peptide with high affinity for these GRPRs. We synthesized DTPA-Q-K-Y-G-N-Q-W-A-V-G-H-L-M, a 13-amino-acid peptide chelated with diethylenetriaminepentaacetic acid (DTPA), and radiolabeled this BN analog with 111InCl(3). Biologic activity of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was evaluated in PC-3 prostate tumor-bearing severely compromised immunodeficient (SCID) mice. The purity of synthesized [DTPA(1), Lys(3), Tyr(4)]-BN was greater than 95%. The radiolabeling efficiency of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN was 96.9% +/- 2.46%. The IC(50) and K(i) of [DTPA(1), Lys(3), Tyr(4)]-BN in the human bombesin 2 receptor were 1.05 +/- 0.46 and 0.83 +/- 0.36 nM, respectively. The K(d) of 111In-[DTPA(1), Lys(3), Tyr(4)]-BN in GRPR-expressing PC-3 tumor cells was 22.9 +/- 6.81 nM. Both biodistribution and micro-SPECT/CT (single-photon emission computed tomography/computed tomography) imaging studies with 111In-[DTPA(1), Lys(3), Tyr(4)]-BN demonstrated the highest uptake at 8 hours postinjection. The Pearson correlation analysis showed a positive correlation of tumor uptake between biodistribution and micro-SPECT/CT semiquantification imaging analysis (r = 0.832). Our results revealed 111In-[DTPA(1), Lys(3), Tyr(4)]-BN has high affinity with BN type 2 receptor. The results demonstrated a good uptake in the GRPR-overexpression of PC-3 tumor-bearing SCID mice. 111In-[DTPA(1), Lys(3), Tyr(4)]-BN is a potential agent for imaging GRPR-positive tumors in humans.

  20. Spectral, thermal and electrochemical characterization of novel homo-dinuclear complexes [M 2(H 3DTPA)(H 2O) 6]Cl 2· xH 2O (M = Cr 2+, Mn 2+, Co 2+, Ni 2+ or Cu 2+)

    NASA Astrophysics Data System (ADS)

    Siddiqi, Zafar A.; Noor, Shabana; Shahid, M.; Khalid, Mohd

    2011-05-01

    The title complexes were prepared and characterized employing spectral (FAB-Mass, IR, electronic, 1H and 13C NMR), thermal and electrochemical techniques. Analytical and FAB-Mass data suggested a homo-dinuclear stoichiometry. IR and electronic ligand field spectral studies coupled with molecular model computations have indicated a distorted octahedral geometry where the ligand coordinates as a hexadentate dianionic [H 3DTPA] 2-(H 5DTPA = diethylenetriaminepentaacetic acid) moiety. The electrochemical redox properties and the antibacterial activities of the compounds were also investigated.

  1. Developing a physiologically based approach for modeling plutonium decorporation therapy with DTPA.

    PubMed

    Kastl, Manuel; Giussani, Augusto; Blanchardon, Eric; Breustedt, Bastian; Fritsch, Paul; Hoeschen, Christoph; Lopez, Maria Antonia

    2014-11-01

    To develop a physiologically based compartmental approach for modeling plutonium decorporation therapy with the chelating agent Diethylenetriaminepentaacetic acid (Ca-DTPA/Zn-DTPA). Model calculations were performed using the software package SAAM II (©The Epsilon Group, Charlottesville, Virginia, USA). The Luciani/Polig compartmental model with age-dependent description of the bone recycling processes was used for the biokinetics of plutonium. The Luciani/Polig model was slightly modified in order to account for the speciation of plutonium in blood and for the different affinities for DTPA of the present chemical species. The introduction of two separate blood compartments, describing low-molecular-weight complexes of plutonium (Pu-LW) and transferrin-bound plutonium (Pu-Tf), respectively, and one additional compartment describing plutonium in the interstitial fluids was performed successfully. The next step of the work is the modeling of the chelation process, coupling the physiologically modified structure with the biokinetic model for DTPA. RESULTS of animal studies performed under controlled conditions will enable to better understand the principles of the involved mechanisms.

  2. Chelating DTPA amphiphiles: ion-tunable self-assembly structures and gadolinium complexes.

    PubMed

    Moghaddam, Minoo J; de Campo, Liliana; Kirby, Nigel; Drummond, Calum J

    2012-10-05

    A series of chelating amphiphiles and their gadolinium (Gd(III)) metal complexes have been synthesized and studied with respect to their neat and lyotropic liquid crystalline phase behavior. These amphiphiles have the ability to form ion-tunable self-assembly nanostructures and their associated Gd(III) complexes have potential as magnetic resonance imaging (MRI) contrast enhancement agents. The amphiphiles are composed of diethylenetriaminepentaacetic acid (DTPA) chelates conjugated to one or two oleyl chain(s) (DTPA-MO and DTPA-BO), or isoprenoid-type chain(s) of phytanyl (DTPA-MP and DTPA-BP). The thermal phase behavior of the neat amphiphiles was examined by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and cross polarizing optical microscopy (POM). Self-assembly of neat amphiphiles and their associated Gd complexes, as well as their lyotropic phase behavior in water and sodium acetate solutions of different ionic strengths, were examined by POM and small and wide angle X-ray scattering (SWAXS). All neat amphiphiles exhibited lamellar structures. The non-complexed amphiphiles showed a variety of lyotropic phases depending on the number and nature of the hydrophobic chain in addition to the ionic state of the hydration. Upon hydration with increased Na-acetate concentration and the subtle changes in the effective headgroup size, the interfacial curvature of the amphiphile increased, altering the lyotropic liquid crystalline structures towards higher order mesophases such as the gyroid (Ia3d) bicontinuous cubic phase. The chelation of Gd with the DTPA amphiphiles resulted in lamellar crystalline structures for all the neat amphiphiles. Upon hydration with water, the Gd-complexed mono-conjugates formed micellar or vesicular self-assemblies, whilst the bis-conjugates transformed only partially into lyotropic liquid crystalline mesophases.

  3. Antibacterial activity of synthetic curcumin derivatives: 3,5-bis(benzylidene)-4-piperidone (EF24) and EF24-dimer linked via diethylenetriaminepentacetic acid (EF2DTPA).

    PubMed

    Vilekar, Prachi; King, Catherine; Lagisetty, Pallavi; Awasthi, Vibhudutta; Awasthi, Shanjana

    2014-04-01

    Curcumin is well known for its antimicrobial and anti-inflammatory properties. However, since systemic absorption and bioavailability of curcumin from gastrointestinal tract is considerably poor, synthetic curcuminoids are being developed as better alternatives. Two curcumin derivatives: 3,5-bis(benzylidene)-4-piperidone (EF24) and EF24-dimer linked via diethylenetriaminepentacetic acid (EF2DTPA), were included in this study. We investigated the antibacterial activity of EF24 and EF2DTPA against Gram-negative (Escherichia coli) and Gram-positive (Enterococcus faecalis, Staphylococcus aureus) bacteria. We also studied the effects of EF24 and EF2DTPA on uptake and localization of pHrodo-labeled E. coli in the acidic compartments (phagolysosomes) of dendritic cells (DCs) under in vitro conditions. Our results demonstrate that treatment with EF24 and EF2DTPA directly suppresses the bacterial growth. However, these compounds do not affect the bacterial uptake or localization in the DCs.

  4. Effectiveness of DTPA treatments following the injection of particulate plutonium.

    PubMed

    Bruenger, F W; Taylor, D M; Taylor, G N; Lloyd, R D

    1991-11-01

    A limited long-term experiment has been completed in which the chronic toxicity resulting from a single intravenous injection of 31.4 kBq of a poly-disperse 239Pu colloid sol per kg of body weight was tested in Beagle dogs. The Pu deposited mostly in the phagocytic cells of liver, spleen and to a lesser degree in lung and bone marrow. Slow solubilization of the Pu particles by endogenous ligands caused translocation of the nuclide and redeposition mostly as monomeric Pu in the skeleton and in liver hepatocytes. Thus, the deposit behaved as expected from a pulmonary or wound contamination in humans with a moderately soluble depot of Pu such as Class W hot particles. Therefore, this type of deposit provided the basis for a practical model to study the ensuing radiation effects under various experimental conditions. The dogs were divided into three groups of four animals each, and the following conditions were applied: (a) no further treatment was given, allowing free translocation of the Pu to its secondary deposition sites; (b) interception of the Pu translocation by weekly injections of 30 mumol of Ca-DTPA/kg of body weight (Ca-chelate of diethylene-triaminepentaacetic acid); and (c) interception of translocation by daily injections of 30 mumol/kg body weight of Zn-DTPA. For each of the groups (b) and (c), three dogs were used in a lifetime study, and one was sacrificed for nuclide distribution studies. Free translocation and subsequent deposition in the skeleton resulted in the death of each of the non-chelated dogs from osteosarcoma between 1267 and 1594 days after injection. Weekly treatment with Ca-DTPA reduced the total Pu burden significantly, but these dogs also died with osteosarcoma between 1462 and 1783 days. Daily injections with Zn-DTPA reduced the total Pu burden more efficiently than Ca-DTPA and prevented continuous deposition of solubilized Pu on bone surfaces. The mean post-injection survival of these dogs was 3520 days or about 2.1 times that of

  5. Enhanced Delivery of Plasmid Encoding Interleukin-12 Gene by Diethylene Triamine Penta-Acetic Acid (DTPA)-Conjugated PEI Nanoparticles.

    PubMed

    Dehshahri, Ali; Sadeghpour, Hossein; Keykhaee, Maryam; Khalvati, Bahman; Sheikhsaran, Fatemeh

    2016-05-01

    Recombinant therapeutic proteins have been considered as an efficient category of medications used for the treatment of various diseases. Despite their effectiveness, there are some reports on the systemic adverse effects of recombinant therapeutic proteins limiting their wide clinical applications. Among different cytokines used for cancer immunotherapy, interleukin-12 (IL-12) has shown great ability as a powerful antitumor and antiangiogenic agent. However, significant toxic reactions following the systemic administration of IL-12 have led researchers to seek for alternative approaches such as the delivery and local expression of the IL-12 gene inside the tumor tissues. In order to transfer the plasmid encoding IL-12 gene, the most extensively investigated polycationic polymer, polyethylenimine (PEI), was modified by diethylene triamine penta-acetic acid (DTPA) to modulate the hydrophobic-hydrophilic balance of the polymer as well as its toxicity. DTPA-conjugated PEI derivatives were able to form complexes in the size range around 100-180 nm with great condensation ability and protection of the plasmid against enzymatic degradation. The highest gene transfer ability was achieved by the DTPA-conjugated PEI at the conjugation degree of 0.1 % where the level of IL-12 production increased up to twofold compared with that of the unmodified PEI. Results of the present study demonstrated that modulation of the surface positive charge of PEI along with the improvement of the polymer hydrophobic balance could be considered as a successful strategy to develop safe and powerful nanocarriers.

  6. Efficacy of orally administered amphipathic polyaminocarboxylic acid chelators for the removal of plutonium and americium: comparison with injected Zn-DTPA in the rat.

    PubMed

    Miller, Scott C; Liu, Gang; Bruenger, Fred W; Lloyd, Ray D

    2006-01-01

    Chelators are used to promote excretion of actinides and some other metals, but few are orally effective. The relative efficacies of orally administered triethylenetetraminepentaacetic acids (TT) with varying lipophilic properties on the removal of 241Am and 239Pu and comparison with parenteral Zn-DTPA was determined. The actinides were administered to adult rats 2 weeks prior to initiation of 30 d of chelation treatment. The TT compounds were given orally while Zn-DTPA was given twice weekly by injection. Total body content of 241Am was measured before and during the treatment period and organ contents of 241Am and 239Pu were measured at the end of the study. Significant reductions in 241Am occurred within the first week, with Zn-DTPA being the most effective. By 3 weeks, the most lipophilic chelator, C22TT was as effective as Zn-DTPA. After 30 d, reductions in organ content of 239Pu and 241Am directly correlated with increasing lipophilicity of the TT chelators. Oral C22TT was as effective as injected Zn-DTPA in liver and bone, the major organs of actinide deposition. The removal of 239Pu from the liver and reduction of redeposition of 239Pu in newly formed bone by C22TT was confirmed by neutron-induced autoradiographs. The amphipathic TT chelators may be useful as orally administered alternatives to current parenteral DTPA for the removal of actinide elements from the body, particularly for longer-term therapeutic applications.

  7. Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo

    PubMed Central

    Xiao, Yan; Zhang, Huafang; Zhang, Zhaoguo; Yan, Mina; Lei, Ming; Zeng, Ke; Zhao, Chunshun

    2013-01-01

    For the purposes of obtaining a hepatocyte-selective drug delivery system, a novel tetravalent galactosylated diethylenetriaminepentaacetic acid-distearoyl phosphatidylethanolamine (4Gal-DTPA-DSPE) was synthesized. The chemical structure of 4Gal-DTPA-DSPE was confirmed by proton nuclear magnetic resonance and mass spectrometry. The four galactose-modified liposomes (4Gal-liposomes) were prepared by thin-film hydration method, then doxorubicin (DOX) was encapsulated into liposomes using an ammonium sulfate gradient loading method. The liposomal formulations with 4Gal-DTPA-DSPE were characterized by laser confocal scanning microscopy and flow cytometry analysis, and the results demonstrated that the 4Gal-liposomes facilitated the intracellular uptake of DOX into HepG2 cells via asialoglycoprotein receptor-mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of 4Gal-liposomes was higher than that of the conventional liposomes without the galactose. Additionally, pharmacokinetic experiments in rats revealed that the 4Gal-liposomes displayed slower clearance from the systemic circulation compared with conventional liposomes. The organ distributions in mice and the study on frozen sections of liver implied that the 4Gal-liposomes enhanced the intracellular uptake of DOX into hepatocytes and prolonged the circulation. Taken together, these results indicate that liposomes containing 4Gal-DTPA-DSPE have great potential as drug delivery carriers for hepatocyte-selective targeting. PMID:23976853

  8. Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte-targeting efficiency in vitro and in vivo.

    PubMed

    Xiao, Yan; Zhang, Huafang; Zhang, Zhaoguo; Yan, Mina; Lei, Ming; Zeng, Ke; Zhao, Chunshun

    2013-01-01

    For the purposes of obtaining a hepatocyte-selective drug delivery system, a novel tetravalent galactosylated diethylenetriaminepentaacetic acid-distearoyl phosphatidylethanolamine (4Gal-DTPA-DSPE) was synthesized. The chemical structure of 4Gal-DTPA-DSPE was confirmed by proton nuclear magnetic resonance and mass spectrometry. The four galactose-modified liposomes (4Gal-liposomes) were prepared by thin-film hydration method, then doxorubicin (DOX) was encapsulated into liposomes using an ammonium sulfate gradient loading method. The liposomal formulations with 4Gal-DTPA-DSPE were characterized by laser confocal scanning microscopy and flow cytometry analysis, and the results demonstrated that the 4Gal-liposomes facilitated the intracellular uptake of DOX into HepG2 cells via asialoglycoprotein receptor-mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of 4Gal-liposomes was higher than that of the conventional liposomes without the galactose. Additionally, pharmacokinetic experiments in rats revealed that the 4Gal-liposomes displayed slower clearance from the systemic circulation compared with conventional liposomes. The organ distributions in mice and the study on frozen sections of liver implied that the 4Gal-liposomes enhanced the intracellular uptake of DOX into hepatocytes and prolonged the circulation. Taken together, these results indicate that liposomes containing 4Gal-DTPA-DSPE have great potential as drug delivery carriers for hepatocyte-selective targeting.

  9. Species-Dependent Chelation of 241Am by DTPA Di-ethyl Ester

    PubMed Central

    Huckle, James E.; Sadgrove, Matthew P.; Mumper, Russell J.; Jay, Michael

    2014-01-01

    Diethylenetriaminepentaacetic acid (DTPA) is an FDA approved chelating agent for enhancing the elimination of transuranic elements such as americium from the body. Early access to therapy minimizes deposition of these radionuclides in tissues such as the bone. Due to its poor oral bioavailability, DTPA is administered as an IV injection, delaying access. Therefore a diethyl-ester analog of DTPA, named C2E2, was synthesized as a means to increase oral absorption. As a hexadentate ligand, it was hypothesized that C2E2 was capable of binding americium directly. Therefore, the protonation constants and americium stability constant for C2E2 were determined by potentiometric titration and a solvent extraction method, respectively. C2E2 was shown to bind americium with a log K of 19.6. The concentrations of C2E2, its metabolite C2E1, and DTPA required to achieve effective binding in rat, beagle, and human plasma were studied in vitro. Dose response curves for each ligand were established and the 50% maximal effective concentrations were determined for each species. As expected, higher concentrations of C2E2 were required to achieve the same degree of binding as DTPA. The results indicated that chelation in beagle plasma is more representative of the human response than rats. Finally, the pharmacokinetics of C2E2 were investigated in beagles and the data was fit to a two-compartment model with elimination from the central compartment, along with first-order absorption. Based on the in vitro data, a 100 mg kg−1 dose of C2E2 can be expected to have an effective duration of action of 3.8 hours in beagles. PMID:25706138

  10. Species-dependent chelation of (241)Am by DTPA Di-ethyl ester.

    PubMed

    Huckle, James E; Sadgrove, Matthew P; Mumper, Russell J; Jay, Michael

    2015-04-01

    Diethylenetriaminepentaacetic acid (DTPA) is an FDA-approved chelating agent for enhancing the elimination of transuranic elements such as americium from the body. Early access to therapy minimizes deposition of these radionuclides in tissues such as the bone. Due to its poor oral bioavailability, DTPA is administered as an IV injection, delaying access. Therefore, a diethyl-ester analog of DTPA, named C2E2, was synthesized as a means to increase oral absorption. As a hexadentate ligand, it was hypothesized that C2E2 was capable of binding americium directly. Therefore, the protonation constants and americium stability constant for C2E2 were determined by potentiometric titration and a solvent extraction method, respectively. C2E2 was shown to bind americium with a log K of 19.6. The concentrations of C2E2, its metabolite C2E1, and DTPA required to achieve effective binding in rat, beagle, and human plasma were studied in vitro. Dose response curves for each ligand were established, and the 50% maximal effective concentrations were determined for each species. As expected, higher concentrations of C2E2 were required to achieve the same degree of binding as DTPA. The results indicated that chelation in beagle plasma is more representative of the human response than rats. Finally, the pharmacokinetics of C2E2 were investigated in beagles, and the data was fit to a two-compartment model with elimination from the central compartment, along with first-order absorption. Based on the in vitro data, a 100 mg kg dose of C2E2 can be expected to have an effective duration of action of 3.8 h in beagles.

  11. Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI.

    PubMed

    Doiron, Amber L; Chu, Kevin; Ali, Adeel; Brannon-Peppas, Lisa

    2008-11-11

    Accurate imaging of atherosclerosis is a growing necessity for timely treatment of the disease. Magnetic resonance imaging (MRI) is a promising technique for plaque imaging. The goal of this study was to create polymeric particles of a small size with high loading of diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) and demonstrate their usefulness for MRI. A water-in-oil-in-oil double emulsion solvent evaporation technique was used to encapsulate the MRI agent in a poly(lactide-co-glycolide) (PLGA) or polylactide-poly(ethylene glycol) (PLA-PEG) particle for the purpose of concentrating the agent at an imaging site. PLGA particles with two separate average sizes of 1.83 microm and 920 nm, and PLA-PEG particles with a mean diameter of 952 nm were created. Loading of up to 30 wt % Gd-DTPA was achieved, and in vitro release occurred over 5 h. PLGA particles had highly negative zeta potentials, whereas the particles incorporating PEG had zeta potentials closer to neutral. Cytotoxicity of the particles on human umbilical vein endothelial cells (HUVEC) was shown to be minimal. The ability of the polymeric contrast agent formulation to create contrast was similar to that of Gd-DTPA alone. These results demonstrate the possible utility of the contrast agent-loaded polymeric particles for plaque detection with MRI.

  12. Cholesterol-diethylenetriaminepentaacetate complexed with thulium ions integrated into bicelles to increase their magnetic alignability.

    PubMed

    Liebi, Marianne; Kuster, Simon; Kohlbrecher, Joachim; Ishikawa, Takashi; Fischer, Peter; Walde, Peter; Windhab, Erich J

    2013-11-27

    Lanthanides have been used for several decades to increase the magnetic alignability of bicelles. DMPE-DTPA (1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylenetriaminepentaacetate) is commonly applied to anchor the lanthanides into the bicelles. However, because DMPE-DTPA has the tendency to accumulate at the highly curved edge region of the bicelles and if located there does not contribute to the magnetic orientation energy, we have tested cholesterol-DTPA complexed with thulium ions (Tm(3+)) as an alternative chelator to increase the magnetic alignability. Differential scanning calorimetric (DSC) measurements indicate the successful integration of cholesterol-DTPA into a DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) bilayer. Cryo transmission electron microscopy and small-angle neutron scattering (SANS) measurements show that the disklike structure, that is, bicelles, is maintained if cholesterol-DTPA·Tm(3+) is integrated into a mixture of DMPC, cholesterol, and DMPE-DTPA·Tm(3+). The size of the bicelles is increased compared to the size of the bicelles obtained from mixtures without cholesterol-DTPA·Tm(3+). Magnetic-field-induced birefringence and SANS measurements in a magnetic field show that with addition of cholesterol-DTPA·Tm(3+) the magnetic alignability of these bicelles is significantly increased compared to bicelles composed of DMPC, cholesterol, and DMPE-DTPA·Tm(3+) only.

  13. Aragonite–calcite–vaterite: A temperature influenced sequential polymorphic transformation of CaCO{sub 3} in the presence of DTPA

    SciTech Connect

    Gopi, Shanmukhaprasad; Subramanian, V.K.; Palanisamy, K.

    2013-05-15

    Highlights: ► Crystallization of CaCO{sub 3} between 60 and 230 °C in the presence of DTPA. ► Formation of exclusive and individual polymorphs at different temperatures. ► Violation of second law of thermodynamics/Ostwald rule of stages has been observed. - Abstract: Calcium carbonate was precipitated from calcium chloride using sodium carbonate in the presence of diethylenetriaminepentaacetic acid (DTPA) between 60 and 230 °C. The samples were characterized by FTIR, Raman, XRD and SEM techniques. CaCO{sub 3} with different crystal morphologies such as spherolite/datura pod, dumbbell, peanut, were obtained depending on the experimental conditions. The results showed that pure aragonite, calcite and vaterite were formed at low, moderate and high temperatures respectively. A binary mixture of calcite and vaterite was resulted between 150 and 200 °C. The data suggested an unusual conversion of stable calcite to meta stable vaterite at higher temperature in presence of DTPA. The study revealed a novel methodology for the exclusive/individual preparation of different crystalline polymorphs of CaCO{sub 3}. Formation of pure vaterite above 200 °C divulged the possibility of DTPA as a potential scale inhibitor and boiler sludge conditioner at elevated temperatures.

  14. Lectin conjugates as biospecific contrast agents for MRI. Coupling of Lycopersicon esculentum agglutinin to linear water-soluble DTPA-loaded oligomers.

    PubMed

    Pashkunova-Martic, Irena; Kremser, Christian; Galanski, Markus; Schluga, Petra; Arion, Vladimir; Debbage, Paul; Jaschke, Werner; Keppler, Bernhard

    2011-06-01

    Magnetic resonance imaging (MRI) requires synthesis of contrast media bearing targeting groups and numerous gadolinium chelating groups generating high relaxivity. This paper explores the results of linking the gadolinium chelates to the targeting group, a protein molecule, via various types of linkers. Polycondensates of diethylenetriaminepentaacetic acid (DTPA) with either diols or diamines were synthesised and coupled to the targeting group, a lectin (Lycopersicon esculentum agglutinin, tomato lectin) which binds with high affinity to specific oligosaccharide configurations in the endothelial glycocalyx. The polycondensates bear up to four carboxylic groups per constitutive unit. Gd-chelate bonds are created through dative interactions with the unshared pair of electrons on each oxygen and nitrogen atom on DTPA. This is mandatory for complexation of Gd(III) and avoidance of the severe toxicity of free gadolinium ions. The polymer-DTPA compounds were characterised by (1)H NMR and mass spectrometry. The final lectin-DTPA-polycondensate conjugates were purified by fast protein liquid chromatography (FPLC). The capacity for specific binding was assessed, and the MRI properties were examined in order to evaluate the use of these oligomers as components of selective perfusional contrast agents.

  15. Clinical assessment of myocardial viability using MRI during a constant infusion of Gd-DTPA.

    PubMed

    Pereira, R S; Wisenberg, G; Prato, F S; Yvorchuk, K

    2000-12-01

    This study assessed the accuracy and feasibility of magnetic resonance imaging (MRI) during a constant infusion of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) for the determination of myocardial viability in patients with recent acute myocardial infarction (AMI). Nine patients were studied within 10 days of AMI. Rest-redistribution 201Thallium (201Tl) single photon emission computed tomography (SPECT) was used as a gold standard for viability. Using MRI, regional perfusion was assessed using dynamic imaging during a bolus injection of Gd-DTPA and viability was assessed during a continuous infusion. Finally, cine MR images were acquired at baseline, during low-dose dobutamine infusion and after recovery. To assess viability, the left ventricle was divided into 16 segments and signal intensity in corresponding MRI and redistribution SPECT segments were compared. Wall thickening index (WTI) was determined at each step during the dobutamine study. The results revealed that in five patients, reduced perfusion in infarcted regions was observed qualitatively during dynamic first pass imaging. There was a significant inverse correlation between 201Tl uptake and MRI signal intensity, i.e. infarcted tissue (low 201Tl uptake) had increased MR signal intensity. Segments were separated into normal (201Tl uptake > 90%) and infarcted (< 601%). lnfarcted MRI segments had greater signal intensity than normal segments (179 +/- 50 vs. 102 +/- 14%; P < 0.0001). WTI in normal segments increased by 18 +/- 8.5% (P < 0.0001) from baseline to 10 microg/kg per min of dobutamine while infarcted tissue WTI decreased 2.8 +/- 7.2% (P = 0.17). Thus regions of myocardium that were infarcted as defined by reduced 201Tl uptake and absent contractile reserve showed greatly increased MRI signal intensity during a constant infusion of Gd-DTPA. The use of MRI during a constant infusion of Gd-DTPA is accurate and feasible for the determination of myocardial necrosis in a clinical setting.

  16. Variability in soil micronutrients extracted by DTPA and Mehlich-3 at the plot scale in an acidic environment

    NASA Astrophysics Data System (ADS)

    Paz-Ferreiro, Jorge; Lado, Marcos; de Abreu, Cleide A.

    2014-05-01

    Land use practices affect soil properties and nutrient supply. Very limited data are available on micronutrient extractability in northwest Spain. The aim of this study was to analyse long-term effects of land use on the concentration, variability and spatial distribution of soil nutrients. To this end, neighboring forest and cultivated stands were compared. The study was carried out in an acid, rich in organic matter soil developed over sediments at the province of Lugo, northwestern of Spain. Adjacent plots with a surface of 100 m2 were marked on regular square grids with 2-m spacing. Fe, Mn, Zn and Cu were extracted both by Mehlich-3 and DTPA solutions and determined by ICP-MS. General soil chemical and physical properties were routinely analyzed. In arable land, microelement concentration ranges were as follows: Fe (100 and 135 mg kg-1), Mn (7.6 and 21.5 mg kg-1), Zn (0.6 and 3.7 mg kg-1), and Cu (0.2 and 0.7 mg kg-1). In forest land, these ranges were: Fe (62 and 309 mg kg-1), Mn (0.2 and 2.1 mg kg-1), Zn (0.2 and 2.9 mg kg-1), and Cu (0.1 and 0.2 mg kg-1). With the exception of Fe-DTPA, microelement concentrations extracted both with DTPA and Mehlich-3 were higher in the cultivated than in the forest stand. Coefficients of variation were higher for the microelement content of the soil under forest. Principal component analysis was performed to evaluate associations between extractable microelements and general physico-chemical properties. At the studied scale, nutrient management was the main factor affecting the agricultural site, whereas soil-plant interactions were probably responsible for the higher variation within the forest site. Patterns of spatial variability of the studied nutrients at the small plot scale also were assessed by geostatistical techniques. Results were discussed in the frame of sustainable land use and organic matter decline with conventional tillage and sustainable land use

  17. Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours.

    PubMed

    Schreiter, Nils F; Brenner, Winfried; Nogami, Munenobu; Buchert, Ralph; Huppertz, Alexander; Pape, Ulrich-Frank; Prasad, Vikas; Hamm, Bernd; Maurer, Martin H

    2012-01-01

    Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies, (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide is still the current standard for diagnosis of neuroendocrine tumours (NET). The aim of this study was to compare the costs for the two diagnostic tests and the respective consequential costs. From January 2009 to July 2009, 51 consecutive patients with enteropancreatic NET who underwent contrast-enhanced (68)Ga-DOTATOC PET/CT (n = 29) or (111)In-DTPA-octreotide (mean 3 whole-body scans plus 1.6 low-dose single photon emission computed tomography/CT; n = 22) were included. For cost analysis, direct costs (equipment) and variable costs (material, labour) per examination were calculated. Additionally required CT and/or MRI examinations within the staging process were assessed as consequential costs. An additional deterministic sensitivity analysis was performed. A (68)Ga-DOTATOC PET/CT examination yielded total costs (equipment, personnel and material costs) of 548 euro. On the other hand, an (111)In-DTPA-octreotide examination resulted in 827 euro total costs. Costs for equipment and material had a share of 460 euro/720 euro for (68)Ga-DOTATOC/(111)In-DTPA-octreotide and labour costs of 89 euro/106 euro. With (68)Ga-DOTATOC additional MRI had to be performed in 7% of the patients resulting in a mean of 20 euro for supplementary imaging per patient; 82% of patients with (111)In-DTPA-octreotide needed additional MRI and/or CT resulting in mean additional costs of 161 euro per patient. (68)Ga-DOTATOC PET/CT was considerably cheaper than (111)In-DTPA-octreotide with respect to both material and personnel costs. Furthermore, by using (68)Ga-DOTATOC PET/CT considerably fewer additional examinations were needed reducing the consequential costs significantly.

  18. Inhomogeneous localization of radioactivity in the human kidney after injection of [(111)In-DTPA]octreotide.

    PubMed

    De Jong, Marion; Valkema, Roelf; Van Gameren, Arthur; Van Boven, Hester; Bex, Axel; Van De Weyer, Eric Pieter; Burggraaf, Jan Dirk; Körner, Meike; Reubi, Jean-Claude; Krenning, Eric P

    2004-07-01

    In peptide receptor radionuclide therapy (PRRT) using somatostatin analogs labeled with beta-emitters, the radiosensitive kidney is the dose-limiting organ, because of high uptake and retention of the radionuclides after glomerular filtration. Dosimetry calculations are mostly based on the MIRD scheme, assuming homogeneous renal radioactivity distribution. The aim of this study was to reveal the radioactivity distribution in the normal human kidney after intravenous injection of [(111)In-diethylenetriaminepentaacetic acid (DTPA)]octreotide. Three patients received intravenous injection of [(111)In-DTPA]octreotide before nephrectomy because of renal cancer. Distribution of radioactivity in the human kidney was investigated using SPECT scanning before and ex vivo autoradiography of the kidney after surgery. Radioactivity was localized predominantly in the cortex of the kidney. In the cortex, radioactivity was not distributed homogeneously but formed a striped pattern, with most of the radioactivity centered in the inner cortical zone. These findings show that average dose calculations using the MIRD scheme, assuming homogeneous renal radioactivity distribution, are inadequate to estimate the radiation dose to various parts of the kidney after PRRT. Different effects due to inhomogeneity can be expected from PRRT using radionuclides emitting particles with short particle ranges, for example, Auger electron emitters, alpha-emitters, and low-energy beta-emitters.

  19. 64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head Comparison with 111In-DTPA-Octreotide in 112 Patients.

    PubMed

    Pfeifer, Andreas; Knigge, Ulrich; Binderup, Tina; Mortensen, Jann; Oturai, Peter; Loft, Annika; Berthelsen, Anne Kiil; Langer, Seppo W; Rasmussen, Palle; Elema, Dennis; von Benzon, Eric; Højgaard, Liselotte; Kjaer, Andreas

    2015-06-01

    Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin analogs. We have previously shown the clinical potential of (64)Cu-DOTATATE in a small first-in-human feasibility study. The aim of the present study was, in a larger prospective design, to compare on a head-to-head basis the performance of (64)Cu-DOTATATE and (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide ((111)In-DTPA-OC) as a basis for implementing (64)Cu-DOTATATE as a routine. We prospectively enrolled 112 patients with pathologically confirmed NETs of gastroenteropancreatic or pulmonary origin. All patients underwent both PET/CT with (64)Cu-DOTATATE and SPECT/CT with (111)In-DTPA-OC within 60 d. PET scans were acquired 1 h after injection of 202 MBq (range, 183-232 MBq) of (64)Cu-DOTATATE after a diagnostic contrast-enhanced CT scan. Patients were followed for 42-60 mo for evaluation of discrepant imaging findings. The McNemar test was used to compare the diagnostic performance. Eighty-seven patients were congruently PET- and SPECT-positive. No SPECT-positive cases were PET-negative, whereas 10 false-negative SPECT cases were identified using PET. The diagnostic sensitivity and accuracy of (64)Cu-DOTATATE (97% for both) were significantly better than those of (111)In-DTPA-OC (87% and 88%, respectively, P = 0.017). In 84 patients (75%), (64)Cu-DOTATATE identified more lesions than (111)In-DTPA-OC and always at least as many. In total, twice as many lesions were detected with (64)Cu-DOTATATE than with (111)In-DTPA-OC. Moreover, in 40 of 112 cases (36%) lesions were detected by (64)Cu-DOTATATE in organs not identified as disease-involved by (111)In-DTPA-OC. With these results, we demonstrate that (64)Cu-DOTATATE is far superior to (111)In-DTPA-OC in diagnostic performance in NET patients. Therefore, we do not hesitate to recommend implementation of (64)Cu-DOTATATE as a replacement for (111)In-DTPA-OC. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  20. Diethylentriaminepenta acetic acid glucose conjugates as a cell permeable iron chelator

    PubMed Central

    Mosayebnia, Mona; Shafiee-Ardestani, Mehdi; Pasalar, Parvin; Mashayekhi, Mojgan; Amanlou, Massoud

    2014-01-01

    Objective: To find out whether DTPA-DG complex can enhance clearance of intracellular free iron. Materials and Methods: Diethylenetriaminepentaacetic acid-D-deoxy-glucosamine (DTPA-DG) was synthesized and examined for its activity as a cell-permeable iron chelator in human hepatocellular carcinoma (HEPG2) cell line exposed to high concentration of iron sulfate and compared with deferoxamine (DFO), a prototype iron chelator. The effect of DTPA-DG on cell viability was monitored using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide MTT assay as well. Results: There was a significant increase of iron level after iron overload induction in HEPG2 cell culture. DTPA-DG presented a remarkable capacity to iron burden reducing with estimated 50% inhibitory concentration value of 65.77 nM. In fact, glycosyl moiety was gained access of DTPA to intracellular iron deposits through glucose transporter systems. Conclusion: DTPA-DG, more potent than DFO to sequester deposits of free iron with no profound toxic effect. The results suggest the potential of DTPA-DG in chelating iron and permitting its excretion from primary organ storage. PMID:24554907

  1. 111In-benzyl-DTPA-ZHER2:342, an affibody-based conjugate for in vivo imaging of HER2 expression in malignant tumors.

    PubMed

    Tolmachev, Vladimir; Nilsson, Fredrik Y; Widström, Charles; Andersson, Karl; Rosik, Daniel; Gedda, Lars; Wennborg, Anders; Orlova, Anna

    2006-05-01

    Data on expression of the HER2 (erbB-2) receptor in breast carcinoma make it possible to select the most efficient treatment. There are strong indications that HER2 expression possesses prognostic and predictive values in ovarian, prostate, and lung carcinomas as well. Visualization of HER2 expression using radionuclide targeting can provide important diagnostic information. The Affibody Z(HER2:342) is a short (approximately 7 kDa) phage-display-selected protein that binds HER2 with an affinity of 22 pmol/L. The goal of this study was to evaluate whether (111)In-labeled HER2:342 can be used for imaging of HER2 overexpression in vivo. Z(HER2:342) was labeled with (111)In via isothiocyanate-benzyl-DTPA (DTPA is diethylenetriaminepentaacetic acid) and the conjugate was characterized in vitro and in vivo. (111)In-Benzyl-DTPA-Z(HER2:342) preserved the capacity to bind living HER2-expressing cells specifically. The affinity of In-benzyl-DTPA-Z(HER2:342) to HER2 was 21 pmol/L according to surface plasmon resonance measurements. In nude mice bearing HER2-expressing SKOV-3 xenografts, a tumor uptake of 12% +/- 3% injected activity per gram and a tumor-to-blood ratio of about 100 were obtained 4 h after injection. Tumor uptake in vivo was receptor specific, as it could be blocked with an excess of nonlabeled Z(HER2:342). HER2-expressing xenografts were clearly imaged 4 h after injection using a gamma-camera. (111)In-Benzyl-DTPA-Z(HER2:342) is a promising candidate for visualization of HER2 expression in carcinomas, using the single-photon detection technique.

  2. Epidermal growth factor receptor inhibition modulates the nuclear localization and cytotoxicity of the Auger electron emitting radiopharmaceutical 111In-DTPA human epidermal growth factor.

    PubMed

    Bailey, Kristy E; Costantini, Danny L; Cai, Zhongli; Scollard, Deborah A; Chen, Zhuo; Reilly, Raymond M; Vallis, Katherine A

    2007-09-01

    (111)In-DTPA-human epidermal growth factor ((111)In-DTPA-hEGF [DTPA is diethylenetriaminepentaacetic acid]) is an Auger electron-emitting radiopharmaceutical that targets EGF receptor (EGFR)-positive cancer. The purpose of this study was to determine the effect of EGFR inhibition by gefitinib on the internalization, nuclear translocation, and cytotoxicity of (111)In-DTPA-hEGF in EGFR-overexpressing MDA-MB-468 human breast cancer cells. Western blot analysis was used to determine the optimum concentration of gefitinib to abolish EGFR activation. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled hEGF were evaluated by confocal microscopy in MDA-MB-468 cells (1.3 x 10(6) EGFRs/cell) in the presence or absence of 1 microM gefitinib. The proportion of radioactivity partitioning into the cytoplasm and nucleus of MDA-MB-468 cells after incubation with (111)In-DTPA-hEGF for 24 h at 37 degrees C in the presence or absence of 1 microM gefitinib was measured by cell fractionation. DNA double-strand breaks caused by (111)In were quantified using the gamma-H2AX assay, and radiation-absorbed doses were estimated. Clonogenic survival assays were used to measure the cytotoxicity of (111)In-DTPA-hEGF alone or in combination with gefitinib. Gefitinib (1 microM) completely abolished EGFR phosphorylation in MDA-MB-468 cells. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled EGF were not diminished in gefitinib-treated cells compared with controls. The proportion of internalized (111)In that localized in the nucleus was statistically significantly greater when (111)In-DTPA-hEGF was combined with gefitinib compared with (111)In-DTPA-hEGF alone (mean +/- SD: 26.0% +/- 5.5% vs. 14.6% +/- 4.0%, respectively; P < 0.05). Induction of gamma-H2AX foci was greater in MDA-MB-468 cells that were treated with (111)In-DTPA-hEGF (250 ng/mL, 1.5 MBq/mL) plus gefitinib (1 microM ) compared with those treated with (111)In-DTPA-hEGF alone (mean

  3. Orally administered DTPA di-ethyl ester for decorporation of (241)Am in dogs: Assessment of safety and efficacy in an inhalation-contamination model.

    PubMed

    Huckle, James E; Sadgrove, Matthew P; Pacyniak, Erik; Leed, Marina G D; Weber, Waylon M; Doyle-Eisele, Melanie; Guilmette, Raymond A; Agha, Bushra J; Susick, Robert L; Mumper, Russell J; Jay, Michael

    2015-07-01

    Currently two injectable products of diethylenetriaminepentaacetic acid (DTPA) are U.S. Food and Drug Administration (FDA)-approved for decorporation of (241)Am; however, an oral product is considered more amenable in a mass casualty situation. The di-ethyl ester of DTPA, named C2E2, is being developed as an oral drug for treatment of internal radionuclide contamination. Single-dose decorporation efficacy of C2E2 administered 24-h post contamination was determined in beagle dogs using a (241)Am nitrate inhalation contamination model. Single and multiple dose toxicity studies in beagle dogs were performed as part of an initial safety assessment program. In addition, the genotoxic potential of C2E2 was evaluated by the in vitro bacterial reverse mutation Ames test, mammalian cell chromosome aberration cytogenetic assay and an in vivo micronucleus test. Oral administration of C2E2 significantly increased (241)Am elimination over untreated controls and significantly reduced the retention of (241)Am in tissues, especially liver, kidney, lung and bone. Daily dosing of 200 mg/kg/day for 10 days was well tolerated in dogs. C2E2 was found to be neither mutagenic or clastogenic. The di-ethyl ester of DTPA (C2E2) was shown to effectively enhance the elimination of (241)Am after oral administration in a dog inhalation-contamination model and was well tolerated in toxicity studies.

  4. Orally Administered DTPA Di-ethyl Ester for Decorporation of 241Am in dogs: Assessment of Safety and Efficacy in an Inhalation-Contamination Model

    PubMed Central

    Huckle, James E.; Sadgrove, Matthew P.; Pacyniak, Erik; Leed, Marina G. D.; Weber, Waylon M.; Doyle-Eisele, Melanie; Guilmette, Raymond A.; Agha, Bushra J.; Susick, Robert L.; Mumper, Russell J.; Jay, Michael

    2016-01-01

    Purpose Currently two injectable products of diethylenetriaminepentaacetic acid (DTPA) are U.S. Food and Drug Administration (FDA) approved for decorporation of 241Am, however, an oral product is considered more amenable in a mass casualty situation. The diethyl ester of DTPA, named C2E2, is being developed as an oral drug for treatment of internal radionuclide contamination. Materials and methods Single dose decorporation efficacy of C2E2 administered 24-hours post contamination was determined in beagle dogs using a 241Am nitrate inhalation contamination model. Single and multiple dose toxicity studies in beagle dogs were performed as part of an initial safety assessment program. In addition, the genotoxic potential of C2E2 was evaluated by the in vitro bacterial reverse mutation Ames test, mammalian cell chromosome aberration cytogenetic assay and an in vivo micronucleus test. Results Oral administration of C2E2 significantly increased 241Am elimination over untreated controls and significantly reduced the retention of 241Am in tissues, especially liver, kidney, lung and bone. Daily dosing of 200 mg/kg/day for 10 days was well tolerated in dogs. C2E2 was found to be neither mutagenic or clastogenic. Conclusions The di-ethyl ester of DTPA (C2E2) was shown to effectively enhance the elimination of 241Am after oral administration in a dog inhalation-contamination model and was well tolerated in toxicity studies. PMID:25912343

  5. Gd-DTPA-Dopamine-Bisphytanyl Amphiphile: Synthesis, Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents.

    PubMed

    Gupta, Abhishek; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; de Campo, Liliana; Hwang, Dennis W; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

    2015-09-28

    Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a Gd(III)-chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd-DTPA-dopamine-bisphytanyl (Gd-DTPA-Dop-Phy), which is readily capable of self-assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.40 T. Analysis of variable temperature (17)O NMR transverse relaxation measurements revealed the water exchange of the nanoassemblies to be faster than that previously reported for paramagnetic liposomes. Molecular reorientation dynamics were probed by (1)H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari-Szabo "model-free" approach. High payloads of Gd(III) ions in the liposomal nanoassemblies made solely from the Gd-DTPA-Dop-Phy amphiphiles, in combination with slow molecular reorientation and fast water exchange makes this novel amphiphile a suitable candidate to be investigated as an advanced MRI contrast agent.

  6. A kit to prepare (111)In-DTPA-trastuzumab (Herceptin) Fab fragments injection under GMP conditions for imaging or radioimmunoguided surgery of HER2-positive breast cancer.

    PubMed

    Scollard, Deborah A; Chan, Conrad; Holloway, Claire M B; Reilly, Raymond M

    2011-01-01

    The human epidermal growth factor receptor-2 (HER2) gene is amplified in 25% of invasive breast cancers, and receptor overexpression has been noted in up to 60% of early stages of the disease [ductal carcinoma in situ (DCIS)]. Preclinical studies have revealed high tumor/blood ratios (>27:1) for (111)In-labeled Fab fragments of the HER2 monoclonal antibody, trastuzumab (Herceptin) ((111)In-DTPA-trastuzumab Fab) at 72 h pi in athymic mice bearing subcutaneous human breast cancer xenografts. Our aim in this study was to formulate a kit for preparation of (111)In-DTPA-trastuzumab Fab injection under good manufacturing practice (GMP) conditions suitable for human administration in a Phase I clinical trial of imaging and radioimmunoguided surgery (RIGS) of HER2-positive breast cancer. Fab fragments were produced by digestion of trastuzumab IgG (Herceptin) with immobilized papain for 20 h at 37°C. Fab fragments were purified by ultrafiltration, then reacted with a 10-fold molar excess of diethylenetriaminepentaacetic acid (DTPA) dianhydride. DTPA-Fab fragments were purified, then sterilized by filtration into unit dose glass vials (kits). Kits were tested against specifications for volume (0.9-1.1 ml), protein concentration (0.45-0.55 mg/ml), pH (5.5-6.5), DTPA substitution (0.5-4.0 mol DTPA/mol Fab), appearance (clear, colorless and particle free), labeling efficiency (≥ 85%), and sterility and apyrogenicity (USP XXXII). Immunoreactivity of (111)In-DTPA-trastuzumab Fab towards HER2 was measured by saturation radioligand binding assays using SKBR-3 human breast cancer cells (specifications: K(a) = 0.6-9.6 × 10(7) L/mol; B(max) = 0.6-10.4 × 10(6) sites/cell). (111)In-DTPA-trastuzumab Fab injection was prepared by adding 80-100 MBq of (111)InCl(3) to a single kit vial and incubating for 30 min at room temperature. (111)In-DTPA-trastuzumab Fab was assayed for the amount of radioactivity and tested for pH, radiochemical purity (RCP), appearance and sterility. Pure and

  7. Complexation of Curium(III) with DTPA at 10–70 °C: Comparison with Eu(III)–DTPA in Thermodynamics, Luminescence, and Coordination Modes

    SciTech Connect

    Tian, Guoxin; Zhang, Zhiyong; Martin, Leigh R.; Rao, Linfeng

    2015-02-16

    Separation of trivalent actinides (An(III)) from trivalent lanthanides (Ln(III)) is a challenging task because of their nearly identical chemical properties. Diethylenetriaminepentaacetate (DTPA), a key reagent used in the TALSPEAK process that effectively separates An(III) from Ln(III), is believed to play a critical role in the An(III)/Ln(III) separation. However, the underlying principles for the separation based on the difference in the complexation of DTPA with An(III) and Ln(III) remain unclear. In this work, the complexation of DTPA with Cm(III) at 10-70 ºC was investigated by spectrophotometry, luminescence spectroscopy, and microcalorimetry, in conjunction with computational methods. The binding strength, the enthalpy of complexation, the coordination modes, and the luminescence properties are compared between the Cm(III)-DTPA and Eu(III)-DTPA systems. The experimental and computational data have demonstrated that the difference between Cm(III) and Eu(III) in the binding strength with DTPA can be attributed to the stronger covalence bonding between Cm(III) and the nitrogen donors of DTPA.

  8. Localization of neurofibromas by scanning with technetium-99m diethylene triamine-pentacetic acid (Tc-99 DTPA)

    SciTech Connect

    Mandell, G.A.; Herrick, W.C.; Harcke, H.T.; Sharkey, C.; Brooks, K.; MacEwen, G.D.

    1985-05-01

    Tc-99m DTPA is commonly utilized to evaluate renal function. Reports of a uterine myoma and a soft tissue sarcoma accumulating this radiopharmaceutical have also appeared in the literature. The authors have observed the affinity for plexiform as well as well circumscribed soft tissue tumors of neurofibromatosis for Tc-99m DTPA. In a series of 16 patients with clinical stigmata of neurofibromatosis, twenty-eight sites of abnormal soft tissue localization of the isotope were documented by clinical and radiographic (predominantly CT) correlation. The best visualization of the tumors occurred 1 to 3 hours post-injection of the radiopharmaceutical. Multiple images (150,000 to 500,000 counts) of areas suspected of having neurofibromatous involvement were obtained. Several unsuspected lesions were recognized. Similar images obtained in sixteen control patients showed no similar soft tissue localization. The smallest lesion detected was a 1.5-centimeter subcutaneous neurofibroma. The mechanism for selectivity of neurofibroma for Tc-99m DTPA does not appear to be related to hypervascularity or necrosis. Time activity curves of several lesions demonstrate gradual increase in their activity pointing to cellular uptake or stasis within the tumor as possible explanations. The significance of this observation relates to easy mapping of lesions with minimal radiation. Important implications of this discovery include sequential evaluation of tumor growth and detection of unsuspected lesions.

  9. Gd-EOB-DTPA-enhanced MRI for evaluation of liver function: Comparison between signal-intensity-based indices and T1 relaxometry

    PubMed Central

    Haimerl, Michael; Verloh, Niklas; Zeman, Florian; Fellner, Claudia; Nickel, Dominik; Lang, Sven A.; Teufel, Andreas; Stroszczynski, Christian; Wiggermann, Philipp

    2017-01-01

    Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a paramagnetic hepatobiliary magnetic resonance (MR) contrast agent. Due to its OATP1B1/B3-dependent hepatocyte-specific uptake and paramagnetic properties increasing evidence has emerged to suggest that Gd-EOB-DTPA-enhanced MRI can be potentially used for evaluation of liver function. In this paper we compare the diagnostic performance of Gd-EOB-DTPA-enhanced relaxometry-based and commonly used signal-intensity (SI)-based indices, including the hepatocellular uptake index (HUI) and SI-based indices corrected by spleen or muscle, for evaluation of liver function, determined using the Indocyanin green clearance (ICG) test. Simple linear regression model showed a significant correlation of the plasma disappearance rate of ICG (ICG-PDR) with all Gd-EOB-DTPA-enhanced MRI-based liver function indices with a significantly better correlation of relaxometry-based indices on ICG-PDR compared to SI-based indices. Among SI-based indices, HUI achieved best correlation on ICG-PDR and no significant difference of respective correlations on ICG-PDR could be shown. Assessment of liver volume and consecutive evaluation of multiple linear regression model revealed a stronger correlation of ICG-PDR with both (SI)-based and T1 relaxometry-based indices. Thus, liver function can be estimated quantitatively from Gd-EOB-DTPA–enhanced MRI-based indices. Here, indices derived from T1 relaxometry are superior to SI-based indices, and all indices benefit from taking into account respective liver volumes. PMID:28266528

  10. Fully automatic region of interest selection in glomerular filtration rate estimation from 99mTc-DTPA renogram.

    PubMed

    Lin, Kun-Ju; Huang, Jia-Yann; Chen, Yung-Sheng

    2011-12-01

    Glomerular filtration rate (GFR) is a common accepted standard estimation of renal function. Gamma camera-based methods for estimating renal uptake of (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) without blood or urine sampling have been widely used. Of these, the method introduced by Gates has been the most common method. Currently, most of gamma cameras are equipped with a commercial program for GFR determination, a semi-quantitative analysis by manually drawing region of interest (ROI) over each kidney. Then, the GFR value can be computed from the scintigraphic determination of (99m)Tc-DTPA uptake within the kidney automatically. Delineating the kidney area is difficult when applying a fixed threshold value. Moreover, hand-drawn ROIs are tedious, time consuming, and dependent highly on operator skill. Thus, we developed a fully automatic renal ROI estimation system based on the temporal changes in intensity counts, intensity-pair distribution image contrast enhancement method, adaptive thresholding, and morphological operations that can locate the kidney area and obtain the GFR value from a (99m)Tc-DTPA renogram. To evaluate the performance of the proposed approach, 30 clinical dynamic renograms were introduced. The fully automatic approach failed in one patient with very poor renal function. Four patients had a unilateral kidney, and the others had bilateral kidneys. The automatic contours from the remaining 54 kidneys were compared with the contours of manual drawing. The 54 kidneys were included for area error and boundary error analyses. There was high correlation between two physicians' manual contours and the contours obtained by our approach. For area error analysis, the mean true positive area overlap is 91%, the mean false negative is 13.4%, and the mean false positive is 9.3%. The boundary error is 1.6 pixels. The GFR calculated using this automatic computer-aided approach is reproducible and may be applied to help nuclear medicine physicians in

  11. The CONRAD approach to biokinetic modeling of DTPA decorporation therapy.

    PubMed

    Breustedt, Bastian; Blanchardon, Eric; Bérard, Philippe; Fritsch, Paul; Giussani, Augusto; Lopez, Maria Antonia; Luciani, Andrea; Nosske, Dietmar; Piechowski, Jean; Schimmelpfeng, Jutta; Sérandour, Anne-Laure

    2010-10-01

    Diethylene Triamine Pentaacetic Acid (DTPA) is used for decorporation of plutonium because it is known to be able to enhance its urinary excretion for several days after treatment by forming stable Pu-DTPA complexes. The decorporation prevents accumulation in organs and results in a dosimetric benefit, which is difficult to quantify from bioassay data using existing models. The development of a biokinetic model describing the mechanisms of actinide decorporation by administration of DTPA was initiated as a task in the European COordinated Network on RAdiation Dosimetry (CONRAD). The systemic biokinetic model from Leggett et al. and the biokinetic model for DTPA compounds of International Commission on Radiological Protection Publication 53 were the starting points. A new model for biokinetics of administered DTPA based on physiological interpretation of 14C-labeled DTPA studies from literature was proposed by the group. Plutonium and DTPA biokinetics were modeled separately. The systems were connected by means of a second order kinetics process describing the chelation process of plutonium atoms and DTPA molecules to Pu-DTPA complexes. It was assumed that chelation only occurs in the blood and in systemic compartment ST0 (representing rapid turnover soft tissues), and that Pu-DTPA complexes and administered forms of DTPA share the same biokinetic behavior. First applications of the CONRAD approach showed that the enhancement of plutonium urinary excretion after administration of DTPA was strongly influenced by the chelation rate constant. Setting it to a high value resulted in a good fit to the observed data. However, the model was not yet satisfactory since the effects of repeated DTPA administration in a short time period cannot be predicted in a realistic way. In order to introduce more physiological knowledge into the model several questions still have to be answered. Further detailed studies of human contamination cases and experimental data will be needed in

  12. Relationship between induction of phosphorylated H2AX and survival in breast cancer cells exposed to 111In-DTPA-hEGF.

    PubMed

    Cai, Zhongli; Chen, Zhuo; Bailey, Kristy E; Scollard, Deborah A; Reilly, Raymond M; Vallis, Katherine A

    2008-08-01

    The Auger electron-emitting radiopharmaceutical 111In-diethylenetriaminepentaacetic acid human epidermal growth factor (111In-DTPA-hEGF) binds the epidermal growth factor receptor (EGFR), is internalized, and translocates to the nucleus. The purpose of this study was to investigate the relationship between EGFR expression, DNA damage, and cytotoxicity in cells exposed to 111In-DTPA-hEGF. Breast cancer cell lines with a range of EGFR expression levels were exposed to 111In-DTPA-hEGF or gamma-radiation. The cell lines (followed by number of EGFR per cell in parentheses) were MDA-MB-468 (1.3 x 10(6)), MDA-MB-231 (1.3 x 10(5)), and MCF-7 (1.5 x 10(4)). The proportion of radioactivity partitioning into the nucleus was measured by cell fractionation. DNA double-strand breaks were evaluated using the gamma-H2AX assay. Clonogenic survival assays were used to measure cytotoxicity. All data are presented as mean +/- SD. The amount of 111In-DTPA-hEGF that translocated to the nucleus (in mBq/nucleus) in MDA-MB-468, MDA-MB-231, and MCF-7 cells incubated with 111In-DTPA-hEGF (5.2 MBq/mL, 43 nM) for 20 h was 131 +/- 6, 8.1 +/- 0.1, and 1.1 +/- 0.9, respectively. The number of gamma-H2AX foci per nucleus was 35 +/- 15, 19 +/- 10, and 1.7 +/- 0.3, respectively. A reduction in the surviving fraction (SF) in MDA-MB-468 (0.013 +/- 0.001) and MDA-MB-231 (0.5 +/- 0.1) but not in MCF-7 cells after exposure to 111In-DTPA-hEGF (5.2 MBq/mL, 43 nM) for 20 h has been demonstrated. The SF of MDA-MB-468 cells after exposure to DTPA-EGF (43 nM) and 111In-acetate (5.2 MBq/mL) for 20 h was 0.5 +/- 0.1 and 0.53 +/- 0.05, respectively. MDA-MB-468 was the most sensitive of the cell lines to gamma-irradiation, with an SF after 2 Gy of 0.45 +/- 0.04, compared with 0.7 +/- 0.1 and 0.8 +/- 0.1 for MCF-7 and MDA-MB-231, respectively. The number of gamma-H2AX foci per nucleus in MDA-MB-468 cells correlated with the concentration, specific activity, and incubation time of 111In-DTPA-hEGF. DNA damage caused

  13. Regional Myocardial Blood Volume and Flow: First-Pass MR Imaging with Polylysine-Gd-DTPA

    PubMed Central

    Wilke, Norbert; Kroll, Keith; Merkle, Hellmut; Wang, Ying; Ishibashi, Yukata; Xu, Ya; Zhang, Jiani; Jerosch-Herold, Michael; Mühler, Andreas; Stillman, Arthur E.; Bassingthwaighte, James B.; Bache, Robert; Ugurbil, Kamil

    2010-01-01

    The authors investigated the utility of an intravascular magnetic resonance (MR) contrast agent, poly-L-lysine-gadolinium diethylenetriaminepentaacetic acid (DTPA), for differentiating acutely ischemic from normally perfused myocardium with first-pass MR imaging. Hypoperfused regions, identified with microspheres, on the first-pass images displayed significantly decreased signal intensities compared with normally perfused myocardium (P < .0007). Estimates of regional myocardial blood content, obtained by measuring the ratio of areas under the signal intensity-versus-time curves in tissue regions and the left ventricular chamber, averaged 0.12 mL/g ± 0.04 (n = 35), compared with a value of 0.11 mL/g ± 0.05 measured with radiolabeled albumin in the same tissue regions. To obtain MR estimates of regional myocardial blood flow, in situ calibration curves were used to transform first-pass intensity-time curves into content-time curves for analysis with a multiple-pathway, axially distributed model. Flow estimates, obtained by automated parameter optimization, averaged 1.2 mL/min/g ± 0.5 [n = 29), compared with 1.3 mL/min/g ± 0.3 obtained with tracer microspheres in the same tissue specimens at the same time. The results represent a combination of T1-weighted first-pass imaging, intravascular relaxation agents, and a spatially distributed perfusion model to obtain absolute regional myocardial blood flow and volume. PMID:7766986

  14. Multi-functional chitosan nanoparticles encapsulating quantum dots and Gd-DTPA as imaging probes for bio-applications.

    PubMed

    Tan, Wee Beng; Zhang, Yong

    2007-07-01

    Chitosan was used to encapsulate both CdSe/ZnS quantum dots (QDs) and the magnetic resonance imaging (MRI) contrast agent gadolinium-diethylenetriaminepentaacetate (Gd-DTPA), forming multi-functional nanoparticles that can be used in a wide range of in vitro or in vivo studies as fluorescent biological labels as well as MRI contrast agents, respectively. Multi-color QDs at pre-determined molar ratios were encapsulated into chitosan nanoparticles to produce bar-coding fluorescent labels. The encapsulated QDs and Gd-DTPA still maintained their desirable optical properties and relatively high relaxivity, respectively. The chitosan nanoparticles also showed good aqueous stability and enhanced biocompatibility on myoblast cells.

  15. Effect of the EGFR density of breast cancer cells on nuclear importation, in vitro cytotoxicity, and tumor and normal-tissue uptake of [111In]DTPA-hEGF.

    PubMed

    Hu, Meiduo; Scollard, Deborah; Chan, Conrad; Chen, Paul; Vallis, Katherine; Reilly, Raymond M

    2007-11-01

    Our objective was to evaluate the effect of epidermal growth factor receptor(s) (EGFR) density on the importation and nuclear localization of 111In-labeled diethylenetriaminepentaacetic acid human epidermal growth factor ([111In]DTPA-hEGF) in breast cancer (BC) cells in vitro and in tumor xenografts and normal tissues in vivo in athymic mice, as well as on its cytotoxicity and tumor and normal-tissue distribution. The internalization and nuclear importation of [111In]DTPA-hEGF were measured in MCF-7, MDA-MB-231, BT-474 and MDA-MB-468 BC cells (10(4), 2 x 10(5), 6 x 10(5) and 10(6) EGFR/cell, respectively). The molecular size (Mr) distribution and immunoreactivity of nuclear radioactivity were characterized. Tumor and normal-tissue uptake of [111In]DTPA-hEGF in athymic mice implanted subcutaneously with BC xenografts were compared. Nuclear radioactivity in the tumor, lungs, liver, kidneys, spleen and colon was measured. There was a direct association between EGFR density and the nuclear localization of [111In]DTPA-hEGF in BC cells; nuclear importation approached saturation at 6 x 10(5) EGFR/cell. Almost all nuclear radioactivities exhibited an Mr of >100 kDa; immunoreactivity with anti-hEGF, anti-EGFR and anti-importin beta 1 antibodies was detected. The efflux of nuclear radioactivity was slowest for MDA-MB-468 cells. Cytotoxicity was correlated with EGFR expression. Uptake was greater in MDA-MB-468 than in MCF-7 xenografts and improved with preinjection of a 100-fold excess of unlabeled DTPA-hEGF. Nuclear importation was higher in liver, kidney and spleen cells than in tumor cells. [111In]DTPA-hEGF is translocated to the nucleus of BC cells complexed with EGFR and importin beta1. Nuclear importation and cytotoxicity are effected by EGFR density. The absence of hepatic and renal toxicities in [111In]DTPA-hEGF cannot be explained by a low efficiency of nuclear importation.

  16. ¹¹¹In-Bn-DTPA-nimotuzumab with/without modification with nuclear translocation sequence (NLS) peptides: an Auger electron-emitting radioimmunotherapeutic agent for EGFR-positive and trastuzumab (Herceptin)-resistant breast cancer.

    PubMed

    Fasih, Aisha; Fonge, Humphrey; Cai, Zhongli; Leyton, Jeffrey V; Tikhomirov, Ilia; Done, Susan J; Reilly, Raymond M

    2012-08-01

    Increased expression of epidermal growth factor receptors (EGFR) in breast cancer (BC) is often associated with trastuzumab (Herceptin)-resistant forms of the disease and represents an attractive target for novel therapies. Nimotuzumab is a humanized IgG(1) monoclonal antibody that is in clinical trials for treatment of EGFR-overexpressing malignancies. We show here that nimotuzumab derivatized with benzylisothiocyanate diethylenetriaminepentaacetic acid for labelling with the subcellular range Auger electron-emitter, (111)In and modified with nuclear translocation sequence (NLS) peptides ((111)In-NLS-Bn-DTPA-nimotuzumab) was bound, internalized and transported to the nucleus of EGFR-positive BC cells. Emission of Auger electrons in close proximity to the nucleus caused multiple DNA double-strand breaks which diminished the clonogenic survival (CS) of MDA-MB-468 cells that have high EGFR density (2.4 × 10(6) receptors/cell) to less than 3 %. (111)In-Bn-DTPA-nimotuzumab without NLS peptide modification was sevenfold less effective for killing MDA-MB-468 cells. (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification were equivalently cytotoxic to MDA-MB-231 and TrR1 BC cells that have moderate EGFR density (5.4 × 10(5) or 4.2 × 10(5) receptors/cell, respectively) reducing their CS by twofold. MDA-MB-231 cells have intrinsic trastuzumab resistance due to low HER2 density, whereas TrR1 cells have acquired resistance despite HER2 overexpression. Biodistribution and microSPECT/CT imaging revealed that (111)In-NLS-Bn-DTPA-nimotuzumab exhibited more rapid elimination from the blood and lower tumour uptake than (111)In-Bn-DTPA-nimotuzumab. Tumour uptake of the radioimmunoconjugates in mice with MDA-MB-468 xenografts was high (8-16 % injected dose/g) and was blocked by administration of an excess of unlabelled nimotuzumab, demonstrating EGFR specificity. We conclude that (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification are promising Auger

  17. Solution structure and dynamics of lanthanide complexes of the macrocyclic polyamino carboxylate DTPA-dien. NMR study and crystal structures of the lanthanum(III) and europium(III) complexes

    SciTech Connect

    Franklin, S.J.; Raymond, K.N.

    1994-12-07

    An 18-membered macrocyclic DTPA-bis(amide) ligand (DTPA = diethylenetriaminepentaacetic acid) containing a heteroatom in the amide link has been prepared via the condensation of DTPA-dianhydride and diethylenetriamine. The solution structures of the two isomeric pairs present in the Ln(III) complexes of DTPA-dien have been investigated by {sup 1}H NMR. The structures of the lanthanum(III) and europium(III) DTPA-dien complexes have been determined by X-ray analysis. [La(DTPA-dienH{sup +})H{sub 2}O]{sub 2}(CF{sub 3}SO{sub 3}{sup -}){sub 2}{center_dot}18H{sub 2}O (I) crystallizes as a carboxylate-bridged dimer about a center of inversion in the orthorhombic space group Pbca with a = 12.626(2) {angstrom}, b = 21.405(3) {angstrom}, c = 26.422(9) {angstrom}, and Z = 8. Each lanthanum ion is 11-coordinate with octadentate ligand coordination, an {eta}{sup 2} bridging carboxylate, and one water. [Eu(DTPA-dienH{sup +})]{sub 4}(CF{sub 3}SO{sub 3}{sup -}){sub 4}{center_dot}6NaCF{sub 3}SO{sub 3}{center_dot}20H{sub 2}O (II) crystallizes as a carboxylate-bridged tetramer with two crystallographically independent Eu(III) positions (Z = 8 for each) in the monoclinic space group C2/c: a = 30.94(1) {angstrom}, b = 23.456(3) {angstrom}, c = 22.611(4) {angstrom}, {beta} = 105.78(2){degrees}. The coordination geometries about Eu1 and Eu2 are nearly identical and are described as a nine-coordinate tricapped trigonal prism with octadentate ligand coordination plus an {eta}{sup 1} bridging carboxylate. The tendency to oligomerize is attributed to the constraints imposed by the macrocycle and the hydrogen bonding available with the link heteroatom. The structural differences between the two complexes are attributed to a difference in La(III) and Eu(III) ionic size.

  18. The role of Tc-99m DTPA aerosol scintigraphy in the differential diagnosis of COPD and asthma.

    PubMed

    Karacavus, Seyhan; Intepe, Yavuz S

    2015-04-01

    Chronic obstructive lung disease (COPD) and asthma are characterized as similar to each other in causing airway obstruction and being an inflammatory process. The purpose of this study was to investigate whether technetium-99m diethylenetriaminepentaacetic acid ((99m) Tc-DTPA) aerosol scintigraphy could be used in the differential diagnosis of asthma and COPD. Eighty-four patients (male/female: 32/52; mean age 50.2 ± 12.7 years) with obstructive lung disease and 30 healthy volunteers as the control group were enrolled in the study. The patients were divided into two groups as COPD and asthma and also smoking subgroups. Alveolar clearance study was performed using a radiolabeled aerosol of (99m) Tc-DTPA. Mucociliary clearance was evaluated with T½ , cap value and penetration index parameters. All patient underwent pulmonary function tests and Forced expiratory volume (FEV1 ), forced vital capacity (FVC) and FEV1 /FVC parameters were obtained. The mean of T½ values of (99m) Tc-DTPA aerosol and FEV1 /FVC value among spirometric tests of the nonsmoking COPD patients were significantly lower than nonsmoking asthma patients (46.1 ± 14.3, 62.3 ± 18.7, P = 0.02; 65.2 ± 10.8, 81.4 ± 16.5, P = 0.04, respectively). The cap value was significantly higher in nonsmoking COPD patients (1.21 ± 0.49, 0.76 ± 0.22, P = 0.03). While there were no statistically and significantly different between control and asthmatic groups at the scintigraphic parameters and spirometric parameters, the mean of T½ values, cap value and spirometric parameters were statistically different between control and COPD groups (P < 0.05). We showed that assessment of mucociliary permeability with (99m) Tc-DTPA aerosol scintigraphy was a useful, easy to apply and a noninvasive technique to use in the differential diagnosis of nonsmoker COPD and asthma. © 2014 John Wiley & Sons Ltd.

  19. Synthesis and Physicochemical Characterization of a Diethyl Ester Prodrug of DTPA and Its Investigation as an Oral Decorporation Agent in Rats.

    PubMed

    Huckle, James E; Sadgrove, Matthew P; Leed, Marina G D; Yang, Yu-Tsai; Mumper, Russell J; Semelka, Richard C; Jay, Michael

    2016-07-01

    The increasing threats of nuclear terrorism have made the development of medical countermeasures a priority for international security. Injectable formulations of diethylenetriaminepentaacetic acid (DTPA) have been approved by the FDA; however, an oral formulation is more amenable in a mass casualty situation. Here, the diethyl ester of DTPA, named C2E2, is investigated for potential as an oral treatment for internal radionuclide contamination. C2E2 was synthesized and characterized using NMR, MS, and elemental analysis. The physiochemical properties of solubility, lipophilicity, and stability were investigated in order to predict its oral bioavailability. Finally, an animal efficacy study was conducted in Sprague Dawley rats pre-contaminated by intramuscular injection with (241)Am(NO3)3 to establish effectiveness of the therapy via the oral route. Synthesis of C2E2 yielded a crystalline powder with high solubility and improved lipophilicity over DTPA. The ester was stable in both simulated gastric and intestinal fluids over the anticipated time course of absorption. Capsules containing C2E2 were demonstrated to be stable for 12 months under accelerated stability conditions. After a single dose, C2E2 enhanced the elimination of (241)Am in a dose-dependent manner. Significant improvement was seen in both total (241)Am decorporation and reduction of (241)Am liver and skeletal burden. C2E2 was concluded to be effective when orally administered to (241)Am-contaminated rats. It may therefore have potential for medical countermeasure in treating humans contaminated with (241)Am or other transuranic elements. An oral capsule or powder for reconstitution may be suitable formulations for future development based on the physiochemical properties and anticipated dose required for efficacy.

  20. Adsorption characteristics of Ni(II) onto MA-DTPA/PVDF chelating membrane.

    PubMed

    Zhao, Xiaodan; Song, Laizhou; Fu, Jie; Tang, Pei; Liu, Feng

    2011-05-30

    The melamine-diethylenetriaminepentaacetic acid/polyvinylidene fluoride (MA-DTPA/PVDF) chelating membrane bearing polyaminecarboxylate groups was prepared for the removal of Ni(II) from wastewater effluents. The membrane was characterized by SEM, (13)C NMR and FTIR techniques. Quantitative adsorption experiments were performed in view of pH, contact time, temperature, the presence of Ca(II) and lactic acid as the controlling parameters. Adsorption kinetics and equilibrium were examined regarding the single Ni(II) system, binary Ni(II) and Ca(II) system and nickel-lactic acid complexes system. The desorption efficiency was also evaluated, and the adsorption mechanism was suggested based on experimental data. The results show that the sorption kinetics fit well to Lagergren second-order equation and the isotherms can be well described by Langmuir model. At 298 K, the second-order rate constant is calculated to be 4.171, 11.39, 6.203 cm(2)/(mg min) and the equilibrium uptake is 0.0264, 0.0211 and 0.0216 mg/cm(2) in the aforementioned three systems. The distribution coefficient of Ni(II) slowly decreases from 4.27 to 2.72, and the separation factor (f(Ni(II)/Ca(II))) increases from 3.10 to 8.46 when the initial Ca(II) concentration varies from 20 to 200mg/L. This reveals the chelating membrane shows more affinity for Ni(II) than Ca(II) ions. In the studied range of lactic acid concentration, Ni(II) uptake decreases with the maximum ratio of 10%. Chemical bonding (chelation) dominates in the adsorption process, and the negative ΔG° and ΔH° indicate the spontaneous and exothermic nature of adsorption.

  1. Regional respiratory clearance of aerosolized /sup 99m/Tc-DTPA: posture and smoking effects

    SciTech Connect

    Dusser, D.J.; Minty, B.D.; Collignon, M.A.; Hinge, D.; Barritault, L.G.; Huchon, G.J.

    1986-06-01

    We studied 10 healthy nonsmokers and 8 healthy smokers, in both the upright and supine position, to investigate whether regional differences in respiratory clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid /sup 99m/Tc-DTPA (RC-DTPA) existed and to assess the influence of posture and smoking on the regional RC-DTPA. RC-DTPA was assessed by the lung clearance rates (%/min) of aerosolized /sup 99m/Tc-DTPA (0.8 micron MMD; 2.4 GSD), using data corrected for recirculating radioactivity, in the upper (zone 1), middle (zone 2), and lower (zone 3) posterior lung fields. In nonsmokers, RC-DTPA in zone 1 was faster than in zone 2 or 3 in both the upright (P less than 0.001) and supine positions (P less than 0.0). No effect was produced by changes in posture on the regional RC-DTPA. In smokers, RC-DTPA was increased in all zones compared with the nonsmokers (P = 0.004), with a further increase in RC-DTP in zone 1 in the upright posture compared with the other regions (P less than 0.001). We conclude that in nonsmokers regional RC-DTPA is faster in zone 1 than in other zones, and this is not related to recirculation of radioactivity; posture does not modify the regional RC-DTPA of nonsmokers; smoking increases RC-DTPA in all zones and more in zone 1 in the upright posture.

  2. A simplified determination of glomerular filtration rate with 99Tcm-DTPA.

    PubMed

    Galli, G; Rufini, V; Meduri, G

    1994-10-01

    Using 99Tcm-diethylenetriaminepentaacetate (DTPA) an acceptable estimate of glomerular filtration rate (GFR) can be obtained in adult patients by the equation GF (ml/min) = (0.14 x W + 5) x 1000 x k, where W is the 'ideal' body mass (kg) and k the slope determined by two plasma samples. This has been verified in comparison with the results of the Russell (two samples) and Christensen (one sample) methods in 50 patients. The procedure, which does not require determination of the injected dose, could be useful in patients undergoing sequential renal scintigraphy with 99Tcm-DTPA, for example, to check a doubtful value of glomerular filtration obtained by external counting.

  3. Calcium and zinc DTPA administration for internal contamination with plutonium-238 and americium-241.

    PubMed

    Kazzi, Ziad N; Heyl, Alexander; Ruprecht, Johann

    2012-08-01

    The accidental or intentional release of plutonium or americium can cause acute and long term adverse health effects if they enter the human body by ingestion, inhalation, or injection. These effects can be prevented by rapid removal of these radionuclides by chelators such as calcium or zinc diethylenetriaminepentaacetate (calcium or zinc DTPA). These compounds have been shown to be efficacious in enhancing the elimination of members of the actinide family particularly plutonium and americium when administered intravenously or by nebulizer. The efficacy and adverse effects profile depend on several factors that include the route of internalization of the actinide, the type, and route time of administration of the chelator, and whether the calcium or zinc salt of DTPA is used. Current and future research efforts should be directed at overcoming limitations associated with the use of these complex drugs by using innovative methods that can enhance their structural and therapeutic properties.

  4. Gadolinium-DTPA enhancement of lung radiation fibrosis

    SciTech Connect

    Werthmuller, W.C.; Schiebler, M.L.; Whaley, R.A.; Mauro, M.A.; McCartney, W.H. )

    1989-11-01

    Gadolinium-diethylenetriamine pentaacetic acid (DTPA) enhancement of radiation-induced apical pulmonary fibrosis was observed in two patients previously treated for breast cancer. In one case the fibrosis was biopsied twice, with no change in its CT appearance over 3 years. Gadolinium-DTPA may enhance benign apical fibrosis after radiation therapy and should not, in and of itself, be used as evidence of recurrent malignancy.

  5. DTPA complexation of bismuth in human blood serum.

    PubMed

    Montavon, G; Le Du, A; Champion, J; Rabung, T; Morgenstern, A

    2012-07-28

    The in vivo(212)Pb/(212)Bi generator is promising for application in targeted alpha therapy (TAT) of cancer. One main limitation of its therapeutic application is due to potential release of (212)Bi from the radioconjugate upon radioactive decay of the mother nuclide (212)Pb, potentially leading to irradiation of healthy tissue. The objective of the present work is to assess whether the chelate CHX-A''-DTPA (N-(2-aminoethyl)-trans-1,2-diaminocyclohexane-N,N',N''-pentaacetic acid) bound to a biological carrier molecule may be able to re-complex released (212)Bi under in vivo conditions to limit its translocation from the target site. CHX-A''-DTPA was bound to bovine gamma globulin (BGG) to mimic a model conjugate and the stability of the Bi-CHX-A''-DTPA-BGG conjugate was studied in blood serum by ultrafiltration. TRLFS experiments using Cm(III) as a fluorescent probe demonstrated that linking CHX-A''-DTPA to BGG does not affect the coordination properties of the ligand. Furthermore, comparable stability constants were observed between Bi(III) and free CHX-A''-DTPA, BGG-bound CHX-A''-DTPA and DTPA. The complexation constants determined between Bi(III) and the chelate molecules are sufficiently high to allow ultra trace amounts of the ligand to efficiently compete with serum transferrin controlling Bi(III) speciation in blood plasma conditions. Nevertheless, CHX-A''-DTPA is not able to complex Bi(III) generated in blood serum because of the strong competition between Bi(III) and Fe(II) for the ligand. In other words, CHX-A''-DTPA is not "selective" enough to limit Bi(iii) release in the body when applying the (212)Pb/(212)Bi in vivo generator.

  6. Gastrointestinal transit measurements in mice with 99mTc-DTPA-labeled activated charcoal using NanoSPECT-CT

    PubMed Central

    2013-01-01

    Background Gastrointestinal (GI) disorders are commonly associated with chronic conditions such as diabetes, obesity, and hypertension. Direct consequences are obstipation or diarrhea as opposite aspects of the irritable bowel syndrome, and more indirectly, alteration of appetite, feeling of fullness, flatulence, bloatedness, and eventually leading to altered absorption of nutrients. Moreover, GI retention and passage times have been recognized as important factors in determining the release site and hence the bioavailability of orally administered drugs. To facilitate the understanding of physiological and pathological processes involved, it is necessary to monitor the gut motility in animal models. Here, we describe a method for studying the GI transit time using technetium-labeled activated charcoal diethylenetriaminepentaacetic acid (99mTc-Ch-DTPA) detected by single-photon emission computed tomography (SPECT). Methods Tc-DTPA was adsorbed onto activated charcoal and administered orally to trypan blue-tainted (n = 4) 129SvEv mice (50 to 80 MBq/animal, n = 11). The exact distribution and movement of radioactivity in the gastrointestinal tract was measured at intervals of 1, 3, 6, 12, and 22 h by SPECT-CT. In addition, in order to validate the imaging of GI transient time, loperamide (0.25 mg/animal, n = 3) was used to delay the GI transit. Results The transit time measured as the peak radioactivity occurring in the rectum was 6 to 7 h after gavaging of 99mTc-Ch-DTPA. After 1 h, the bolus had passed into the small intestine and entered the cecum and the colon. At 6 and 8 h, the cecum, the ascending, transverse, and descending colon, and the rectum showed significant labeling. Several pellets were stored in the rectum for defecation. After 22 h, little activity remained in the stomach and none was detected in the transverse colon or other GI locations. In contrast, 6 h after administration of loperamide, only the cecum and part of the transverse colon were labeled

  7. Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.

    PubMed

    Li, Guolin; Slansky, Adam; Dobhal, Mahabeer P; Goswami, Lalit N; Graham, Andrew; Chen, Yihui; Kanter, Peter; Alberico, Ronald A; Spernyak, Joseph; Morgan, Janet; Mazurchuk, Richard; Oseroff, Allan; Grossman, Zachary; Pandey, Ravindra K

    2005-01-01

    A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important

  8. Renal damage caused by warm ischaemia during laparoscopic and robot-assisted partial nephrectomy: an assessment using Tc 99m-DTPA glomerular filtration rate.

    PubMed

    Choi, Jae Duck; Park, Jong Wook; Choi, Joon Young; Kim, Hong Seok; Jeong, Byong Chang; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Seo, Seong Il

    2010-12-01

    Few studies assessing the functional change of each kidney following warm ischaemia after partial nephrectomy are available. Our aim was to identify the effects of the warm ischaemic time (WIT) on renal function after partial nephrectomy under the pneumoperitoneum. Forty-four consecutive patients who underwent laparoscopic partial nephrectomy (LPN) or robot-assisted partial nephrectomy (RAPN) from June 2008 to May 2009 for a single cT1 renal tumour were included in this prospective protocol. Technetium Tc 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scintigraphy was used to determine the glomerular filtration rate (GFR) of both kidneys and each kidney individually. Tc 99m-DTPA GFR was performed preoperatively and 3 mo postoperatively. In addition, we analysed Tc 99m-DTPA scintigraphy GFR regionally in the healthy areas of the affected kidney. Patients with WIT > 28 min had a significantly greater decrease in the GFR of the affected kidney (p = 0.031). The GFR of the affected kidney showed a significant decrease perioperatively (46.4 ± 14.3 to 37.9 ± 11.9 ml/min per 1.73 m²; p = 0.003). The functional change of the nonaffected kidney showed an increasing trend (47.5 ± 13.8 to 51.4 ± 14.3 ml/min per 1.73 m²), although it was not statistically significant (p=0.103). Regional Tc 99m-DTPA GFR of both affected kidney and nonaffected kidney showed no significant differences perioperatively (6.3 ± 1.8 to 6.1 ± 1.9 ml/min per 1.73 m²; p = 0.641; 6.6 ± 1.9 to 7.1 ± 2.0 ml/min per 1.73 m² ; p = 0.200). On multivariate analysis, preoperative GFR, resected volume of marginal healthy tissue, and WIT were independent predictors for functional reduction of the affected kidney (p < 0.05). The study was limited by small numbers and short follow-up periods. Stationary overall renal function after LPN or RAPN is masked possibly by functional compensation of the contralateral healthy kidney. The damage of the affected kidney estimated by scintigraphy occurs

  9. Growth and reactivity of silver clusters in amino polycarboxylic acid solutions.

    PubMed

    Kapoor, Sudhir; Mukherjee, Tulsi

    2003-08-01

    Reduction and subsequent aggregation of silver ions in the presence of various chelating agents such as trans-1,2-diaminocyclohexanetetraacetic acid (DCTA) 1,2-propylenediaminetetraacetic acid (PDTA), diethylenetriaminepentaacetic acid (DTPA), and triethylenetetraaminehexaacetic acid (TTHA) have been studied by pulse radiolysis. Rate constants of formation and transient absorption spectra for the ligand-complexed Ag(0) and Ag(2)(+) have been determined. The redox potential of Ag(+)(L)/Ag(0)(L) becomes more negative than that of Ag(+)/Ag(0). Growth and reactivity of silver clusters were also studied in the presence of methyl viologen (MV(2+)). The kinetics of formation of the MV(+*) radical, produced by the same pulse as in the case of silver atoms, confirms the catalytic electron transfer toward super critical silver clusters in the presence of ligands. The results suggest that catalytic electron transfer activity of silver clusters depends on the ligand.

  10. Spectroscopic studies on interaction of BSA and Eu(III) complexes with H5ph-dtpa and H5dtpa ligands

    NASA Astrophysics Data System (ADS)

    Kong, Deyong; Qin, Cui; Fan, Ping; Li, Bing; Wang, Jun

    2015-04-01

    An novel aromatic aminopolycarboxylic acid ligand, N-(2-N,N-Dicarboxymethylaminophenyl) ethylenediamine-N,N‧,N‧-triacetic acid (H5ph-dtpa), was synthesized by improving experimental method and its corresponding Eu(III) complex, Na2[EuIII(ph-dtpa)(H2O)]·6H2O, was successfully prepared through heat-refluxing method. As a comparison, the Eu(III) complex with diethylenetriamine-N,N,N‧,N‧,N″-pentaacetic acid (H5dtpa) ligand, Na2[EuIII(dtpa)(H2O)]·6H2O, was also prepared by the same method. And then, the interaction between prepared Eu(III) complexes ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) and bovine serum albumin (BSA) in aqueous solution were studied by the combination of ultraviolet-visible (UV-vis), fluorescence and circular dichroism (CD) spectroscopies. In addition, the binding sites of Eu(III) complexes ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) to BSA molecules were also estimated by synchronous fluorescence. Moreover, the theoretical and experimental results show that the Van der Waals, hydrogen bond and π-π stacking interactions are the mainly impulse to the reaction. The binding distances (r) between Eu(III) complexes ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) and BSA were obtained according to Förster's non-radiative energy transfer theory. Also, the determined UV-vis absorption spectroscopy, synchronous fluorescence and circular dichroism (CD) spectra showed that the conformation of BSA could be changed in the presence of Eu(III) complexes. The obtained results can help understand the action mode between rare earth metal complexes of aminopolycarboxylic acid ligands with BSA and they are also expected to provide important information of designs of new inspired drugs.

  11. Comparison of Renal Function between Robot-Assisted and Open Partial Nephrectomy as Determined by Tc 99m-DTPA Renal Scintigraphy

    PubMed Central

    2016-01-01

    We compared postoperative renal function impairment between patients undergoing robot-assisted partial nephrectomy (RAPN) and those undergoing open partial nephrectomy (OPN) by using Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. Patients who underwent partial nephrectomy by a single surgeon between 2007 and 2013 were eligible and were matched by propensity score, based on age, tumor size, exophytic properties of tumor, and location relative to the polar lines. Of the 403 patients who underwent partial nephrectomy, 114 (28%) underwent RAPN and 289 (72%) underwent OPN. Mean follow-up duration was 35.2 months. Following propensity matching, there were no significant differences between the two groups in tumor exophytic properties (P = 0.818) or nephrometry score (P = 0.527). Renal ischemic time (24.4 minutes vs. 17.8 minutes, P < 0.001) was significantly longer in the RAPN group than in the OPN group, while the other characteristics were similar. Multivariate analysis showed that greater preoperative renal unit function (P = 0.011) and nephrometry score (P = 0.041) were independently correlated with a reduction in glomerular filtration rate. The operative method did not correlate with renal function impairment (P = 0.704). Postoperative renal function impairment was similar between patients who underwent OPN and those who underwent RAPN, despite RAPN having a longer ischemic time. PMID:27134496

  12. Comparison of Renal Function between Robot-Assisted and Open Partial Nephrectomy as Determined by Tc 99m-DTPA Renal Scintigraphy.

    PubMed

    Lee, Chanwoo; Kwon, Taekmin; Yoo, Sangjun; Jung, Jaeyoon; Lee, Chunwoo; You, Dalsan; Jeong, In Gab; Kim, Choung-Soo

    2016-05-01

    We compared postoperative renal function impairment between patients undergoing robot-assisted partial nephrectomy (RAPN) and those undergoing open partial nephrectomy (OPN) by using Tc-99m diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. Patients who underwent partial nephrectomy by a single surgeon between 2007 and 2013 were eligible and were matched by propensity score, based on age, tumor size, exophytic properties of tumor, and location relative to the polar lines. Of the 403 patients who underwent partial nephrectomy, 114 (28%) underwent RAPN and 289 (72%) underwent OPN. Mean follow-up duration was 35.2 months. Following propensity matching, there were no significant differences between the two groups in tumor exophytic properties (P = 0.818) or nephrometry score (P = 0.527). Renal ischemic time (24.4 minutes vs. 17.8 minutes, P < 0.001) was significantly longer in the RAPN group than in the OPN group, while the other characteristics were similar. Multivariate analysis showed that greater preoperative renal unit function (P = 0.011) and nephrometry score (P = 0.041) were independently correlated with a reduction in glomerular filtration rate. The operative method did not correlate with renal function impairment (P = 0.704). Postoperative renal function impairment was similar between patients who underwent OPN and those who underwent RAPN, despite RAPN having a longer ischemic time.

  13. Liquid hyper-absorption as a cause of increased DTPA clearance in the cystic fibrosis airway

    PubMed Central

    2013-01-01

    Background Airway liquid hyper-absorption is a key pathophysiological link between the genetic mutations of cystic fibrosis (CF) and the development of lung disease. Here we consider whether the clearance of radiolabeled diethylene triamine pentaacetic acid (DTPA) might be used to detect changes in airway liquid absorption. Methods Tc99m-DTPA was added to the apical (luminal) surface of primary human bronchial epithelial cell cultures from CF and non-CF lungs. Liquid absorption rates were assessed using an optical method and compared to DTPA absorption rates. Measurements of transepithelial electrical resistance (TER) were made to determine the effect of epithelial permeability. DTPA absorption was assessed after stimuli known to influence liquid absorption (volume addition and osmotic gradients) and in cultures containing different proportions of CF and non-CF cells. Results DTPA absorption rate was increased in CF cultures matching previous in vivo studies in individuals with CF. DTPA and liquid absorption rates were proportional. There was no relationship between TER and DTPA absorption rate when measured in individual cultures. Apical volume addition increased both DTPA and liquid absorption rates. DTPA absorption increased in a dose-dependent manner after basolateral mannitol addition was used to create transepithelial osmotic gradients favoring liquid absorption. Conversely, apical mannitol (a candidate therapy) slowed DTPA absorption in CF cultures. Conclusions These results imply that DTPA absorption is directly related to liquid absorption, consistent with increased rates of airway surface liquid absorption in the CF airway, and that modification of liquid absorption from osmotic therapies might be detectable through DTPA absorption measurements in vivo. Trial registration none PMID:23446051

  14. Influence of DTPA Treatment on Internal Dose Estimates.

    PubMed

    Davesne, Estelle; Blanchardon, Eric; Peleau, Bernadette; Correze, Philippe; Bohand, Sandra; Franck, Didier

    2016-06-01

    In case of internal contamination with plutonium materials, a treatment with diethylene triamine pentaacetic acid (DTPA) can be administered in order to reduce plutonium body burden and consequently avoid some radiation dose. DTPA intravenous injections or inhalation can start almost immediately after intake, in parallel with urinary and fecal bioassay sampling for dosimetric follow-up. However, urine and feces excretion will be significantly enhanced by the DTPA treatment. As internal dose is calculated from bioassay results, the DTPA effect on excretion has to be taken into account. A common method to correct bioassay data is to divide it by a factor representing the excretion enhancement under DTPA treatment by intravenous injection. Its value may be based on a nominal reference or observed after a break in the treatment. The aim of this study was to estimate the influence of this factor on internal dose by comparing the dose estimated using default or upper and lower values of the enhancement factor for 11 contamination cases. The observed upper and lower values of the enhancement factor were 18.7 and 63.0 for plutonium and 24.9 and 28.8 for americium. For americium, a default factor of 25 is proposed. This work demonstrates that the use of a default DTPA enhancement factor allows the determination of the magnitude of the contamination because dose estimated could vary by a factor of 2 depending on the value of the individual DTPA enhancement factor. In case of significant intake, an individual enhancement factor should be determined to obtain a more reliable dose assessment.

  15. Comparative biodistribution of potential anti-glioblastoma conjugates [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF in normal mice.

    PubMed

    Tolmachev, Vladimir; Orlova, Anna; Wei, Qichun; Bruskin, Alexander; Carlsson, Jörgen; Gedda, Lars

    2004-08-01

    EGF-receptors (EGFR) are overexpressed in gliomas, as well as in tumors of breast, lung, and urinary bladder. For this reason, EGFR may be an attractive target for both visualization and therapy of malignant tumors using radioactive nuclides. Natural ligand of EGFR, epidermal growth factor (EGF) is a small 53-amino-acid protein. Low molecular weight of EGF may enable better intratumoral penetration in comparison to antibodies. [111In]DTPA-EGF was proposed for the targeting of glioblastoma and breast cancer, and its tumor-seeking properties were confirmed in animal studies. The aim of this study was to evaluate how the substitution of heptadentate DTPA for octadentate benzyl-DTPA (Bz-DTPA) effects the biodistribution of indium-labeled human EGF (hEGF) in normal NMRI mice. [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF, obtained by the coupling of ITC-benzyl-DTPA to hEGF, were injected into the tail vein. At 0.5, 1, 4, and 24 hours postinjection, the animals were sacrificed, and radioactivity in different organs was measured. The blood clearance of both conjugates was fast. The uptake of both conjugates in the liver, spleen, stomach, pancreas, intestines, and submaxillary gland was most likely receptor-mediated. The uptake in a majority of organs was similar. However, indium uptake in the case of [111In]DTPA-hEGF was significantly higher in the kidneys and bones. In conclusion, [111In]Bz-DTPA-hEGF seems to have more favourable in vivo distribution in comparison to [111In]DTPA-hEGF.

  16. Tin-117m-labeled stannic (Sn/sup 4 +/) chelate of diethylenetriamine pentaacetic acid (DTPA) for application in diagnosis and therapy

    DOEpatents

    Srivastava, S.C.; Meinken, G.E.; Richards, P.

    1983-08-25

    The radiopharmaceutical reagents of this invention and the class of Tin-117m radiopharmaceuticals are therapeutic and diagnostic agents that incorporate gamma-emitting nuclides that localize in bone after intravenous injection in mammals (mice, rats, dogs, and rabbits). Images reflecting bone structure or function can then be obtained by a scintillation camera that detects the distribution of ionizing radiation emitted by the radioactive agent. Tin-117m-labeled chelates of stannic tin localize almost exclusively in cortical bone. Upon intravenous injection of the reagent, the preferred chelates are phosphonate compounds, preferable, PYP, MDP, EHDP, and DTPA. This class of reagents is therapeutically and diagnostically useful in skeletal scintigraphy and for the radiotherapy of bone tumors and other disorders.

  17. Bifunctional DTPA-type ligand

    SciTech Connect

    Gansow, O.A.; Brechbiel, M.W.

    1990-03-26

    The subject matter of the invention relates to bifunctional cyclohexyl DTPA ligands and methods of using these compounds. Specifically, such ligands are useful for radiolabeling proteins with radioactive metals, and can consequently be utilized with respect to radioimmunoimaging and/or radioimmunotherapy.

  18. Ventilation-perfusion SPECT with 99mTc-DTPA versus Technegas: a head-to-head study in obstructive and nonobstructive disease.

    PubMed

    Jögi, Jonas; Jonson, Björn; Ekberg, Marie; Bajc, Marika

    2010-05-01

    Lung scintigraphy is primarily used to diagnose pulmonary embolism. Ventilation imaging is often performed using (99m)Tc-DTPA or Technegas, an ultrafine dispersion of (99m)Tc-labeled carbon. Despite the common use of these radioaerosols, they have not been compared in an intraindividual study, and not with ventilation-perfusion (V/P) SPECT. The aim of the present head-to-head study was to systematically investigate differences in ventilation studies performed with (99m)Tc-diethylenetriaminepentaacetate (DTPA) and Technegas. Sixty-three patients, 28 without and 35 with obstructive lung disease, were examined with V/P SPECT using both (99m)Tc-DTPA and Technegas. V/P SPECT images were randomized and assessed independently by 2 masked physicians according to a predefined scoring system. A paired comparison was performed using the Wilcoxon signed-rank test. In both obstructive and nonobstructive disease, the overall unevenness of radiotracer deposition and the degree of central deposition were more pronounced in (99m)Tc-DTPA than Technegas studies. Because of better peripheral penetration, the extent of reverse mismatch was less when Technegas was used. Additionally, in obstructive disease, the degree of focal deposition in distal airways was more pronounced with (99m)Tc-DTPA. Mismatched perfusion defects were more frequently found with Technegas in obstructive disease. This intraindividual comparative study shows that Technegas is the preferred radioaerosol, particularly in obstructive disease.

  19. Adsorption of Pb and Zn from binary metal solutions and in the presence of dissolved organic carbon by DTPA-functionalised, silica-coated magnetic nanoparticles.

    PubMed

    Hughes, D L; Afsar, A; Harwood, L M; Jiang, T; Laventine, D M; Shaw, L J; Hodson, M E

    2017-09-01

    The ability of diethylenetriaminepentaacetic acid (DTPA)-functionalised, silica-coated magnetic nanoparticles to adsorb Pb and Zn from single and bi-metallic metal solutions and from solutions containing dissolved organic carbon was assessed. In all experiments 10 mL solutions containing 10 mg of nanoparticles were used. For single metal solutions (10 mg L(-1) Pb or Zn) at pH 2 to 8, extraction efficiencies were typically >70%. In bi-metallic experiments, examining the effect of a background of either Zn or Pb (0.025 mmol L(-1)) on the adsorption of variable concentrations (0-0.045 mmol L(-1)) of the other metal (Pb or Zn, respectively) adsorption was well modelled by linear isotherms (R(2) > 0.60; p ≤ 0.001) and Pb was preferentially adsorbed relative to Zn. In dissolved organic carbon experiments, the presence of fulvic acid (0, 2.1 and 21 mg DOC L(-1)) reduced Pb and Zn adsorption from 0.01, 0.1 and 1.0 mmol L(-1) solutions. However, even at 21 mg DOC L(-1) fulvic acid, extraction efficiencies from 0.01 to 0.1 mmol L(-1) solutions remained >80% (Pb) and >50% (Zn). Decreases in extraction efficiency were significant between initial metal concentrations of 0.1 and 1.0 mmol L(-1) indicating that at metal loadings between c. 100 mg kg(-1) and 300 mg kg(-1) occupancy of adsorption sites began to limit further adsorption. The nanoparticles have the potential to perform effectively as metal adsorbents in systems containing more than one metal and dissolved organic carbon at a range of pH values. Copyright © 2017. Published by Elsevier Ltd.

  20. Preparation of 111In-DTPA morpholino oligomer for low abdominal accumulation

    PubMed Central

    Liu, Guozheng; Dou, Shuping; Rusckowski, Mary; Greiner, Dale; Hnatowich, Donald

    2010-01-01

    An ability to quantitate the beta cell mass by noninvasive nuclear imaging will be very useful in the prevention, diagnosis, and treatment of diabetes. However, to be successful, radioactivity from the pancreas must not be obscured by the background radioactivity in the abdomen. Pretargeting offers the promise of achieving high target organ to normal tissue ratios. In preparation for pancreas imaging studies by pretargeting using morpholino oligomers (MORF/cMORF), it was necessary to develop a simple and efficient method to radiolabel the cMORF effector. Because we have shown that labeling the cMORF with 111In via DTPA reduces excretion into the intestines compared to labeling with 99mTc via MAG3, the conjugation of DTPA to cMORF were investigated for the 111In labeling. The amine-derivatized cMORF was conjugated with DTPA using EDC (1-Ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride) as an alternative to the conventional cyclic anhydride. The conjugation efficiency (represented by the number of DTPA groups attached per cMORF) was investigated by changing the EDC, DTPA and cMORF molar ratios. Different open columns were considered for the purification of DTPA-cMORF. Before conjugation, each cMORF molecule was confirmed to have an amine by trinitrobenzene sulfonic acid (TNBS) assay using the ω-amino butyric acid as positive standrad and the non-amine derivatized cMORF as negative standard. The average number of DTPA groups per cMORF was 0.15–0.20 following the conjugation with DTPA over a cMORF/DTPA molar ratio of 0.5 to 5 and over a cMORF/EDC molar ratio of 20 to 60. The conjugation efficiency was lower than expected probably due to steric hindrance. A 1×50 cm P-4 column using ammonia acetate as eluting buffer provided an adequate separation of DTPA-cMORF from free DTPA. The 111In labeling efficiency by transchelation from acetate exceeded 95%, thus avoiding the need for postlabeling purification. Despite the lower than expected conjugation efficiency

  1. MADOR: a new tool to calculate decrease of effective doses in human after DTPA therapy.

    PubMed

    Fritsch, P; Grémy, O; Hurtgen, C; Bérard, P; Grappin, L; Poncy, J L

    2011-03-01

    Abstract models have been developed to describe dissolution of Pu/Am/Cm after internal contamination by inhalation or wound, chelation of actinides by diethylene triamine penta acetic acid (DTPA) in different retention compartments and excretion of actinide-DTPA complexes. After coupling these models with those currently used for dose calculation, the modelling approach was assessed by fitting human data available in IDEAS database. Good fits were obtained for most studied cases, but further experimental studies are needed to validate some modelling hypotheses as well as the range of parameter values. From these first results, radioprotection tools are being developed: MAnagement of DOse Reduction after DTPA therapy.

  2. Molecular imaging of alpha v beta3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA.

    PubMed

    Burtea, Carmen; Laurent, Sophie; Murariu, Oltea; Rattat, Dirk; Toubeau, Gérard; Verbruggen, Alfons; Vansthertem, David; Vander Elst, Luce; Muller, Robert N

    2008-04-01

    The integrin alpha v beta3 is highly expressed in atherosclerotic plaques by medial and intimal smooth muscle cells and by endothelial cells of angiogenic microvessels. In this study, we have assessed non-invasive molecular magnetic resonance imaging (MRI) of plaque-associated alpha v beta3 integrin expression on transgenic ApoE-/- mice with a low molecular weight peptidomimetic of Arg-Gly-Asp (mimRGD) grafted to gadolinium diethylenetriaminepentaacetate (Gd-DTPA-g-mimRGD). The analogous compound Eu-DTPA-g-mimRGD was employed for an in vivo competition experiment and to confirm the molecular targeting. The specific interaction of mimRGD conjugated to Gd-DTPA or to 99mTc-DTPA with alpha v beta3 integrin was furthermore confirmed on Jurkat T lymphocytes. The mimRGD was synthesized and conjugated to DTPA. DTPA-g-mimRGD was complexed with GdCl3.6H2O, EuCl3.6H2O, or with [99mTc(CO)3(H2O)3]+. MRI evaluation was performed on a 4.7 T Bruker imaging system. Blood pharmacokinetics of Gd-DTPA-g-mimRGD were assessed in Wistar rats and in c57bl/6j mice. The presence of angiogenic blood vessels and the expression of alpha v beta3 integrin were confirmed in aorta specimens by immunohistochemistry. Gd-DTPA-g-mimRGD produced a strong enhancement of the external structures of the aortic wall and of the more profound layers (possibly tunica media and intima). The aortic lumen seemed to be restrained and distorted. Pre-injection of Eu-DTPA-g-mimRGD diminished the Gd-DTPA-g-mimRGD binding to atherosclerotic plaque and confirmed the specific molecular targeting. A slower blood clearance was observed for Gd-DTPA-g-mimRGD, as indicated by a prolonged elimination half-life and a diminished total clearance. The new compound is potentially useful for the diagnosis of vulnerable atherosclerotic plaques and of other pathologies characterized by alpha v beta3 integrin expression, such as cancer and inflammation. The delayed blood clearance, the significant enhancement of the signal

  3. Spectroscopic studies on interaction of BSA and Eu(III) complexes with H5ph-dtpa and H5dtpa ligands.

    PubMed

    Kong, Deyong; Qin, Cui; Fan, Ping; Li, Bing; Wang, Jun

    2015-04-05

    An novel aromatic aminopolycarboxylic acid ligand, N-(2-N,N-Dicarboxymethylaminophenyl) ethylenediamine-N,N',N'-triacetic acid (H5ph-dtpa), was synthesized by improving experimental method and its corresponding Eu(III) complex, Na2[EuIII(ph-dtpa)(H2O)]·6H2O, was successfully prepared through heat-refluxing method. As a comparison, the Eu(III) complex with diethylenetriamine-N,N,N',N',N″-pentaacetic acid (H5dtpa) ligand, Na2[Eu(III)(dtpa)(H2O)]·6H2O, was also prepared by the same method. And then, the interaction between prepared Eu(III) complexes ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) and bovine serum albumin (BSA) in aqueous solution were studied by the combination of ultraviolet-visible (UV-vis), fluorescence and circular dichroism (CD) spectroscopies. In addition, the binding sites of Eu(III) complexes ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) to BSA molecules were also estimated by synchronous fluorescence. Moreover, the theoretical and experimental results show that the Van der Waals, hydrogen bond and π-π stacking interactions are the mainly impulse to the reaction. The binding distances (r) between Eu(III) complexes ([EuIII(dtpa)(H2O)]2- and [EuIII(ph-dtpa)(H2O)]2-) and BSA were obtained according to Förster's non-radiative energy transfer theory. Also, the determined UV-vis absorption spectroscopy, synchronous fluorescence and circular dichroism (CD) spectra showed that the conformation of BSA could be changed in the presence of Eu(III) complexes. The obtained results can help understand the action mode between rare earth metal complexes of aminopolycarboxylic acid ligands with BSA and they are also expected to provide important information of designs of new inspired drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Complications in complexation kinetics for lanthanides with DTPA using dye probe molecules in aqueous solution

    DOE PAGES

    Larsson, K.; Cullen, T. D.; Mezyk, S. P.; ...

    2017-05-17

    The complexation kinetics for the polyaminopolycarboxylic ligand DTPA to lanthanides in acidic aqueous solution were investigated using the dye ligand displacement technique and stopped-flow spectroscopy. Significant rate differences were obtained for different dye probes used, indicating that the kinetics of the dissociation of the dye molecule significantly impacts the overall measured kinetics when using this common methodology. The conditions of the solution also influenced the dye-lanthanide-DTPA interactions, which reconciled previously disparate data in the literature.

  5. Preparation of (111)In-DTPA morpholino oligomer for low abdominal accumulation.

    PubMed

    Liu, Guozheng; Dou, Shuping; Rusckowski, Mary; Greiner, Dale; Hnatowich, Donald

    2010-09-01

    An ability to quantitate the beta cell mass by noninvasive nuclear imaging will be very useful in the prevention, diagnosis, and treatment of diabetes. However, to be successful, radioactivity from the pancreas must not be obscured by the background radioactivity in the abdomen. Pretargeting offers the promise of achieving high target organ to normal tissue ratios. In preparation for pancreas imaging studies by pretargeting using morpholino oligomers (MORF/cMORF), it was necessary to develop a simple and efficient method to radiolabel the cMORF effector. Because we have shown that labeling the cMORF with (111)In via DTPA reduces excretion into the intestines compared to labeling with (99m)Tc via MAG(3), the conjugation of DTPA to cMORF was investigated for (111)In labeling. The amine-derivatized cMORF was conjugated with DTPA using 1-ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) as an alternative to the conventional cyclic anhydride. The conjugation efficiency (represented by the number of DTPA groups attached per cMORF) was investigated by changing the EDC, DTPA, and cMORF molar ratios. Different open columns were considered for the purification of DTPA-cMORF. Before conjugation, each cMORF molecule was confirmed to have an amine by trinitrobenzene sulfonic acid (TNBS) assay using the omega-amino butyric acid as positive standard and the non-amine derivatized cMORF as negative standard. The average number of DTPA groups per cMORF was 0.15-0.20 following the conjugation over a cMORF/DTPA molar ratio of 0.5-5 and over a cMORF/EDC molar ratio of 20-60. The conjugation efficiency was lower than expected probably due to steric hindrance. A 1 x 50cm P-4 column using ammonium acetate as eluting buffer provided an adequate separation of DTPA-cMORF from free DTPA. The (111)In labeling efficiency by transchelation from acetate exceeded 95%, thus avoiding the need for postlabeling purification. Despite the lower than expected conjugation efficiency in which

  6. Effects of sustained exercise on pulmonary clearance of aerosolized sup 99m Tc-DTPA

    SciTech Connect

    Lorino, A.M.; Meignan, M.; Bouissou, P.; Atlan, G. )

    1989-11-01

    The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized {sup 99m}Tc-labeled diethylenetriaminepentaacetate ({sup 99m}Tc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. {sup 99m}Tc-DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O{sub 2} uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency.

  7. Tracheal blood flow and luminal clearance of [sup 99m][Tc]-DTPA in sheep

    SciTech Connect

    Hanafi, Z.; Corfield, D.R.; Webber, S.E.; Widdicombe, J.G. )

    1992-10-01

    Tracheal blood flow and [sup 99m][Tc]-labeled diethylenetriamine pentaacetic acid (DTPA) clearance were measured in the sheep trachea in vivo. The tracheal arteries were isolated and perfused. An isolated segment of tracheal lumen was filled with Krebs-Henseleit solution containing [sup 99m][Tc]-DTPA, and radioactivity was measured in blood from a catheterized tracheal vein. Infusions at constant pressure of methacholine (n=5), albuterol (n=6), and histamine (n=5) increased arterial inflow and venous outflow but decreased [sup 99m][Tc]-DTPA output and concentration. Phenylephrine (n=9) decreased arterial inflow and venous outflow but increased [sup 99m][Tc]-DTPA output and concentration. When the tracheal arteries were initially perfused at constant flow and the flow rate was then changed, 50% increases in flow (n=5) increased perfusion pressure and venous outflow but decreased [sup 99m][Tc]-DTPA output and concentration. Decreases in flow of 50% (n=3) and 100% (n=10) decreased perfusion pressure and venous outflow but increased [sup 99m][Tc]-DTPA output and concentration. Infusion of the same drugs at constant flow produced significant changes in perfusion pressure but no significant changes in venous outflow or, except for histamine, in [sup 99m][Tc]-DTPA output. Thus [sup 99m][Tc]-DTPA output was inversely related to both mechanically and drug-induced changes in tracheal blood flow but, except for histamine, was not directly affected by the drugs. The results may be due to redistribution of blood between collateral circuits and altered interstitial fluid volume affecting [sup 99m][Tc]-DTPA transport across the interstitium. 24 refs., 6 figs., 3 tabs.

  8. Preclinical pharmacokinetic, biodistribution, toxicology, and dosimetry studies of 111In-DTPA-human epidermal growth factor: an auger electron-emitting radiotherapeutic agent for epidermal growth factor receptor-positive breast cancer.

    PubMed

    Reilly, Raymond M; Chen, Paul; Wang, Judy; Scollard, Deborah; Cameron, Ross; Vallis, Katherine A

    2006-06-01

    Our objective was to evaluate the pharmacokinetics, normal tissue distribution, radiation dosimetry, and toxicology of human epidermal growth factor (hEGF) labeled with (111)In ((111)In-diethylenetriaminepentaacetic acid [DTPA]-hEGF) in mice and rabbits. (111)In-DTPA-hEGF (3.6 MBq; 1.3 or 13 microg) was administered intravenously to BALB/c mice. The blood concentration-time data were fitted to a 3-compartment model. Acute toxicity was studied with female BALB/c mice at 42 times the maximum planned human dose (MBq/kg) or with New Zealand White rabbits at 1 times the maximum planned human dose (MBq/kg) for a phase I clinical trial. Toxicity was evaluated by monitoring body weight, by determination of hematology and clinical biochemistry parameters, and by morphologic examination of tissues. Radiation dosimetry projections in humans were estimated on the basis of the residence times in mice by use of the OLINDA version 1.0 computer program. The largest amounts of radioactivity were taken up by the liver (41.3 +/- 7.8 [mean +/- SD] percentage injected dose [%ID] at 1 h after injection and decreasing to 4.9 +/- 0.3 %ID at 72 h after injection) and kidneys (18.6 +/- 0.8 %ID at 1 h and decreasing to 4.5 +/- 0.2 %ID at 72 h after injection). (111)In-DTPA-hEGF was cleared rapidly from the blood, with a half-life at alpha-phase of 2.7-6.2 min and a half-life at beta-phase of 24.0-36.3 min. The half-life of the long terminal phase could not be accurately determined. The volume of distribution of the central compartment was 340-375 mL/kg, and the volume of distribution at steady state was 430-685 mL/kg. There was no significant difference in the ratio of body weight at 15 d to pretreatment weight for mice administered (111)In-DTPA-hEGF (1.02 +/- 0.01) and mice administered unlabeled DTPA-hEGF (1.01 +/- 0.01). Erythrocyte, leukocyte, and platelet counts and serum alanine aminotransferase and creatinine levels remained in the normal ranges. No morphologic changes were observed

  9. Predictive performance of eGFR equations in South Africans of African and Indian ancestry compared with ⁹⁹mTc-DTPA imaging.

    PubMed

    Madala, Nomandla D; Nkwanyana, Ntombifikile; Dubula, Thozama; Naiker, Indiran P

    2012-06-01

    South African guidelines for early detection and management of chronic kidney disease (CKD) recommend using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations for calculating estimated glomerular filtration rate (eGFR) with the correction factor, 1.212, included for MDRD-eGFR in black patients. We compared eGFR against technetium-99m-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) imaging. Using clinical records, we retrospectively recorded demographic, clinical, and laboratory data as well as (99m)Tc-DTPA-measured GFR (mGFR) results obtained from routine visits. Data from 148 patients of African (n = 91) and Indian (n = 57) ancestry were analyzed. Median (IQR) mGFR was 38.5 (44) ml/min/1.73 m(2), with no statistical difference between African and Indian patients (P = 0. 573). In African patients with stage 3 CKD, MDRD-eGFR (unadjusted for black ethnicity) overestimated mGFR by 5.3% [2.0 (16.0) ml/min/1.73 m(2)] compared to CG-eGFR and MDRD-eGFR (corrected for black ethnicity) that overestimated mGFR by 17.7% [6.0 (15.0) ml/min/1.73 m(2)] and 17.1% [6.0 (17.5) ml/min/1.73 m(2)], respectively. In stage 1-2, CKD eGFR overestimated mGFR by 52.5, 38.0, and 19.3% for CG, MDRD (ethnicity-corrected), and MDRD (without correction), respectively. In Indian stage 3 CKD patients, MDRD-eGFR underestimated mGFR by 35.6% [-21.0 (6.5) ml/min/1.73 m(2)] and CG-eGFR by 4.4% [-2.0 (27.0) ml/min/1.73 m(2)], while in stage 1-2 CKD, CG-eGFR and MDRD-eGFR overestimated mGFR by 13.8 and 6.3%, respectively. MDRD-eGFR calculated without the African-American correction factor improved GFR prediction in African CKD patients and using the MDRD correction factor of 1.0 in Indian patients as in Caucasians may be inappropriate.

  10. Evaluation of 188Re-DTPA-deoxyglucose as a potential cancer radiopharmaceutical.

    PubMed

    Chen, Yue; Xiong, Qing-Feng; Yang, Xi-Qun; He, Ling; Huang, Zhan-Wen

    2010-03-01

    We aimed to synthesize diethylenetriamine pentaacetic acid-deoxyglucose (DTPA-DG) radiolabeled with (188)Re and to evaluate its biologic characteristics using mammary tumor-bearing mice. The biodistribution of the radiolabeled compound was determined by tissue counting at 3, 12, and 24 hours after injection in experimental animals. Scintigraphic examinations of nude mice bearing breast cancer (MCF-7 cells) were performed after (188)Re-DTPA-DG (18.5 MBq) was injected in the tail vein. For the tumor inhibitory portion of this work, tumor volumes were measured and recorded every 3 days until the 21st day after injection. The radiochemical purity of (188)Re-DTPA-DG was 95.0%. Based on biodistribution measurements, (188)Re-DTPA-DG was taken up at high levels by the tumor. The mean tumoral percent injected dosages per gram (% ID/g) were 1.98 +/- 0.29 (SD), 2.89 +/- 0.43, and 0.42 +/- 0.06 % ID/g at 3, 12, and 24 hours, respectively, after injection. In the (188)Re-DTPA-DG scintigraphic examinations, the tumors were clearly delineated on the images recorded 2, 4, 8, 12, and 24 hours after injection. In the tumor inhibitory evaluations, the tumor volume of the (188)Re-DTPA-DG-treated group increased more slowly than that of the control groups, which were treated with (188)Re-perrhenate or saline (p < 0.01). Rhenium-188-DTPA-DG showed excellent tumor targeting and tumor growth suppression properties on MCF-7 tumor cells. Rhenium-188-DTPA-DG may be a potential agent for the diagnosis and radiotherapy of tumors.

  11. Redesign of negatively charged (111)In-DTPA-octreotide derivative to reduce renal radioactivity.

    PubMed

    Oshima, Nobuhiro; Akizawa, Hiromichi; Kawashima, Hidekazu; Zhao, Songji; Zhao, Yan; Nishijima, Ken-Ichi; Kitamura, Yoji; Arano, Yasushi; Kuge, Yuji; Ohkura, Kazue

    2017-05-01

    Radiolabeled octreotide derivatives have been studied as diagnostic and therapeutic agents for somatostatin receptor-positive tumors. To prevent unnecessary radiation exposure during their clinical application, the present study aimed to develop radiolabeled peptides which could reduce radioactivity levels in the kidney at both early and late post-injection time points by introducing a negative charge with an acidic amino acid such as L-aspartic acid (Asp) at a suitable position in (111)In-DTPA-conjugated octreotide derivatives. Biodistribution of the radioactivity was evaluated in normal mice after administration of a novel radiolabeled peptide by a counting method. The radiolabeled species remaining in the kidney were identified by comparing their HPLC data with those obtained by alternative synthesis. The designed and synthesized radiolabeled peptide (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide exhibited significantly lower renal radioactivity levels than those of the known (111)In-DTPA-d-Phe(1)-octreotide at 3 and 24h post-injection. The radiolabeled species in the kidney at 24h after the injection of new octreotide derivative represented (111)In-DTPA-d-Phe-OH and (111)In-DTPA-d-Phe-Asp-OH as the metabolites. Their radiometabolites and intact (111)In-DTPA-conjugated octreotide derivative were observed in urine within 24h post-injection. The present study provided a new example of an (111)In-DTPA-conjugated octreotide derivative having the characteristics of both reduced renal uptake and shortened residence time of radioactivity in the kidney. It is considered that this kinetic control was achieved by introducing a negative charge on the octreotide derivative thereby suppressing the reabsorption in the renal tubules and affording the radiometabolites with appropriate lipophilicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Combining octyl(phenyl)-N,N-diisobutyl-carbamoylmethylphosphine oxide and bis-(2-ethylhexyl)phosphoric acid extractants for recovering transuranic elements from irradiated nuclear fuel

    SciTech Connect

    Lumetta, Gregg J.; Carter, Jennifer C.; Gelis, Artem V.; Vandegrift, George F.

    2009-10-14

    Advanced concepts for closing the nuclear fuel cycle include separating Am and Cm from other fuel components. Separating these elements from the lanthanide elements at an industrial scale remains a significant technical challenge. We describe here a chemical system in which a neutral extractant--octyl(phenyl)-N,N-diisobutyl-carbamoylmethyl-phosphine oxide (CMPO)--is combined with an acidic extractant--bis-(2-ethylhexyl)phosphoric acid (HDEHP)--to form a single process solvent (with dodecane as the diluent) for separating Am and Cm from the other components of irradiated nuclear fuel. Continuous variation experiments in which the relative CMPO and HDEHP concentrations are varied indicate a synergistic relationship between the two extractants in the extraction of Am from buffered diethylenetriaminepentaacetic acid (DTPA) solutions. A solvent mixture consisting or 0.1 M CMPO + 1 M HDEHP in dodecane offers acceptable extraction efficiency for the trivalent lanthanides and actinides from 1 M HNO3 while maintaining good lanthanide/actinide separation factors in the stripping regime (buffered DTPA solutions with pH 3.5 to 4). Using citrate buffer instead of lactate buffer results in improved lanthanide/actinide separation factors.

  13. 2,4-Dichlorophenoxyacetic acid (2,4-D) degradation promoted by nanoparticulate zerovalent iron (nZVI) in aerobic suspensions.

    PubMed

    Correia de Velosa, Adriana; Pupo Nogueira, Raquel F

    2013-05-30

    Reactive species generated by Fe(0) oxidation promoted by O2 (catalyzed or not by ligands) are able to degrade contaminant compounds like the herbicide 2,4-dichlorophenoxyacetic acid. The degradation of 2,4-D was influenced by the concentrations of zero valent iron (ZVI) and different ligands, as well as by pH. In the absence of ligands, the highest 2,4-D degradation rate was obtained at pH 3, while the highest percentage degradation (50%) was achieved at pH 5 after 120 min of reaction. Among the ligands studied (DTPA, EDTA, glycine, oxalate, and citrate), only ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) significantly enhanced oxidation of 2,4-D. This increase in oxidation was observed at all pH values tested (including neutral to alkaline conditions), indicating the feasibility of the technique for treatment of contaminated water. In the presence of EDTA, the oxidation rate was greater at pH 3 than at pH 5 or 7. Increasing the EDTA concentration increased the rate and percentage of 2,4-D degradation, however increasing the Fe(0) concentration resulted in the opposite behavior. It was found that degradation of EDTA and 2,4-D occurred simultaneously, and that the new methodology avoided any 2,4-D removal by adsorption/coprecipitation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. DISTRIBUTION OF LANTHANIDE AND ACTINIDE ELEMENTS BETWEEN BIS-(2-ETHYLHEXYL)PHOSPHORIC ACID AND BUFFERED LACTATE SOLUTIONS CONTAINING SELECTED COMPLEXANTS

    SciTech Connect

    Rudisill, Tracy S.; Diprete, David P.; Thompson, Major C.

    2013-04-15

    With the renewed interest in the closure of the nuclear fuel cycle, the TALSPEAK process is being considered for the separation of Am and Cm from the lanthanide fission products in a next generation reprocessing plant. However, an efficient separation requires tight control of the pH which likely will be difficult to achieve on a large scale. To address this issue, we measured the distribution of lanthanide and actinide elements between aqueous and organic phases in the presence of complexants which were potentially less sensitive to pH control than the diethylenetriaminepentaacetic (DTPA) used in the process. To perform the extractions, a rapid and accurate method was developed for measuring distribution coefficients based on the preparation of lanthanide tracers in the Savannah River National Laboratory neutron activation analysis facility. The complexants tested included aceto-, benzo-, and salicylhydroxamic acids, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), and ammonium thiocyanate (NH{sub 4}SCN). The hydroxamic acids were the least effective of the complexants tested. The separation factors for TPEN and NH{sub 4}SCN were higher, especially for the heaviest lanthanides in the series; however, no conditions were identified which resulted in separations factors which consistently approached those measured for the use of DTPA.

  15. Design and synthesis of novel adenine fluorescence probe based on Eu(III) complexes with dtpa-bis(guanine) ligand

    NASA Astrophysics Data System (ADS)

    Tian, Fengyun; Jiang, Xiaoqing; Dou, Xuekai; Wu, Qiong; Wang, Jun; Song, Youtao

    2017-05-01

    A novel adenine (Ad) fluorescence probe (EuIII-dtpa-bis(guanine)) was designed and synthesized by improving experimental method based on the Eu(III) complex and dtpa-bis(guanine) ligand. The dtpa-bis(guanine) ligand was first synthesized by the acylation action between dtpaa and guanine (Gu), and the corresponding Eu(III) complex was successfully prepared through heat-refluxing method with dtpa-bis(guanine) ligand. As a novel fluorescence probe, the EuIII-dtpa-bis(guanine) complex can detect adenine (Ad) with characteristics of strong targeting, high specificity and high recognition ability. The detection mechanism of the adenine (Ad) using this probe in buffer solution was studied by ultraviolet-visible (UV-vis) and fluorescence spectroscopy. When the EuIII-dtpa-bis(guanine) was introduced to the adenine (Ad) solution, the fluorescence emission intensity was significantly enhanced. However, adding other bases such as guanine (Gu), xanthine (Xa), hypoxanthine (Hy) and uric acid (Ur) with similar composition and structure to that of adenine (Ad) to the EuIII-dtpa-bis(guanine) solution, the fluorescence emission intensities are nearly invariable. Meanwhile, the interference of guanine (Gu), xanthine (Xa), hypoxanthine (Hy) and uric acid (Ur) on the detection of the adenine using EuIII-dtpa-bis(guanine) probe was also studied. It was found that presence of these bases does not affect the detection of adenine (Ad). A linear response of fluorescence emission intensities of EuIII-dtpa-bis(guanine) at 570 nm as a function of adenine (Ad) concentration in the range of 0.00-5.00 × 10- 5 mol L- 1 was observed. The detection limit is about 4.70 × 10- 7 mol L- 1.

  16. Design and synthesis of novel adenine fluorescence probe based on Eu(III) complexes with dtpa-bis(guanine) ligand.

    PubMed

    Tian, Fengyun; Jiang, Xiaoqing; Dou, Xuekai; Wu, Qiong; Wang, Jun; Song, Youtao

    2017-02-24

    A novel adenine (Ad) fluorescence probe (Eu(III)-dtpa-bis(guanine)) was designed and synthesized by improving experimental method based on the Eu(III) complex and dtpa-bis(guanine) ligand. The dtpa-bis(guanine) ligand was first synthesized by the acylation action between dtpaa and guanine (Gu), and the corresponding Eu(III) complex was successfully prepared through heat-refluxing method with dtpa-bis(guanine) ligand. As a novel fluorescence probe, the Eu(III)-dtpa-bis(guanine) complex can detect adenine (Ad) with characteristics of strong targeting, high specificity and high recognition ability. The detection mechanism of the adenine (Ad) using this probe in buffer solution was studied by ultraviolet-visible (UV-vis) and fluorescence spectroscopy. When the Eu(III)-dtpa-bis(guanine) was introduced to the adenine (Ad) solution, the fluorescence emission intensity was significantly enhanced. However, adding other bases such as guanine (Gu), xanthine (Xa), hypoxanthine (Hy) and uric acid (Ur) with similar composition and structure to that of adenine (Ad) to the Eu(III)-dtpa-bis(guanine) solution, the fluorescence emission intensities are nearly invariable. Meanwhile, the interference of guanine (Gu), xanthine (Xa), hypoxanthine (Hy) and uric acid (Ur) on the detection of the adenine using Eu(III)-dtpa-bis(guanine) probe was also studied. It was found that presence of these bases does not affect the detection of adenine (Ad). A linear response of fluorescence emission intensities of Eu(III)-dtpa-bis(guanine) at 570nm as a function of adenine (Ad) concentration in the range of 0.00-5.00×10(-5)molL(-1) was observed. The detection limit is about 4.70×10(-7)molL(-1).

  17. Synthesis and evaluation of novel polysaccharide-Gd-DTPA compounds as contrast agent for MRI

    NASA Astrophysics Data System (ADS)

    Sun, Guoying; Feng, Jianghua; Jing, Fengying; Pei, Fengkui; Liu, Maili

    2003-09-01

    Macromolecular conjugates of two kinds of natural polysaccharides, that from Panax quinquefolium linn (PQPS) and Ganoderma applanatum pat (GAPS), with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) have been synthesized and characterized by means of FTIR, elementary analysis and ICP-AES. Their stability was investigated by competition study with Ca 2+, EDTA (ethylenediaminetetraacetic acid) and DTPA. Polysaccharide-bound complexes exhibit T1 relaxivities of 1.5-1.7 times that of Gd-DTPA in D 2O at 25°C and 9.4 T. MR imaging of Sprague-Dawley (SD) rats showed remarkable enhancement in rat liver and kidney after i.v. injection of these two complexes: liver parenchyma 60.9±5.6%, 57.8±7.4% at 65-85 min; kidney 144.9±14.5%, 199.9±25.4% at 10-30 min for PQPS-Gd-DTPA, GAPS-Gd-DTPA at gadolinium dose of 0.083 and 0.082 mmol/kg, respectively. Our preliminary in vivo and in vitro study indicates that the two kinds of polysaccharide-bound complexes are potential tissue-specific contrast agents for MRI.

  18. Evaluations of cellular proliferation and chromosome breakages after in vitro exposure of human lymphocytes to calcium or zinc DTPA

    SciTech Connect

    Littlefield, L.G.; Joiner, E.E.; Colyer, S.P.; DuFrain, R.J.; Washburn, L.C.

    1984-07-01

    The analysis of mitotic indices (MI) and chromosome breakages in metaphases of 50-hr lymphocyte cultures exposed to the calcium or zinc chelates of diethylenetriamine pentaacetic acid (DTPA) demonstrated: (1) an 80% reduction in MI in cultures from three women but no reduction in those from two men after in vitro exposure to CaDTPA in concentrations as low as 10..mu..g/ml culture medium, and complete suppression of mitoses in cultures from men and women after exposure to 40 ..mu..g/ml CaDTPA; (2) minor suppression in MI in cultures from women and none in those from men after exposure to 40 or 80 ..mu..g/ml ZnDTPA; (3) no ring or dicentric chromosomes in 1700 metaphases from DTPA-treated cultures. Likewise, the authors observed no differences in the frequency or distributions of rings and dicentrics in lymphocyte cultures from two persons after in vitro exposure to 250-R /sup 60/Co ..gamma.. radiation in the presence or absence of 10 ..mu..g/ml CaDTPA or 10 or 80 ..mu..g/ml ZnDTPA.

  19. Evaluating the toxicity of novel Zn-DTPA tablet formulation in dogs and rats.

    PubMed

    Shankar, Gita N; Potharaju, Suresh; Green, Carol E

    2014-02-01

    The purpose of this research work is to evaluate toxicity of diethylenetriamine pentaacetic acid zinc trisodium salt (Zn-DTPA) tablets, a novel oral solid dosage form containing permeation enhancers in beagle dogs and Sprague Dawley rats. (Zn-DTPA) in tablet dosage form was administered once daily for 7 days to beagle dogs at low (840 mg/dog/day), mid (2520 mg/dog/day), or high (7560 mg/dog/day). On day 8, all treated and control groups were necropsied. The novel Zn-DTPA tablet formulation showed rapid absorption with the T(max) at 1 h. Plasma concentrations as high as 270 μg/mL were observed after 7 days of administration. Exposure to DTPA, based on area under the curve (AUC(last)) and maximum concentration (C(max)), was dose dependent but not dose proportional. No biologically relevant changes in hematology or clinical chemistry that were related to DTPA exposure were observed, and there were no changes in body weight in treated dogs compared with controls. Zn-DTPA was well tolerated, with minor toxicological effects of emesis and diarrhea, following oral tablet administration for 7 consecutive days. Based on the endpoints evaluated in this study, the maximum tolerated dose is considered to be greater than 7560 mg/dog/day (2535 μmol/kg/day, 1325 mg/kg/day), and the no-observed-adverse-effect level (NOAEL) is considered to be approximately 1325 mg/kg/day per oral when given to male and female beagle dogs. For rats, the NOAEL was estimated to be greater than 1000 mg/kg/day when administered by oral gavage of the crushed Zn-DTPA tablets as suspension once daily (qd) to male and female Sprague Dawley rats. © 2013 Wiley Periodicals, Inc.

  20. Assessment of Gd-EOB-DTPA-enhanced MRI for HCC and dysplastic nodules and comparison of detection sensitivity versus MDCT.

    PubMed

    Inoue, Tatsuo; Kudo, Masatoshi; Komuta, Mina; Hayaishi, Sosuke; Ueda, Taisuke; Takita, Masahiro; Kitai, Satoshi; Hatanaka, Kinuyo; Yada, Norihisa; Hagiwara, Satoru; Chung, Hobyung; Sakurai, Toshiharu; Ueshima, Kazuomi; Sakamoto, Michiie; Maenishi, Osamu; Hyodo, Tomoko; Okada, Masahiro; Kumano, Seishi; Murakami, Takamichi

    2012-09-01

    We aimed to evaluate gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinomas (HCCs) and dysplastic nodules (DNs) compared with dynamic multi-detector row computed tomography (MDCT), and to discriminate between HCCs and DNs. Eighty-six nodules diagnosed as HCC or DNs were retrospectively investigated. Gd-EOB-DTPA-enhanced MRI and dynamic MDCT were compared with respect to their diagnostic ability for hypervascular HCCs and detection sensitivity for hypovascular tumors. The ability of hepatobiliary images of Gd-EOB-DTPA-enhanced MRI to discriminate between these nodules was assessed. We also calculated the EOB enhancement ratio of the tumors. For hypervascular HCCs, the diagnostic ability of Gd-EOB-DTPA-enhanced MRI was significantly higher than that of MDCT for tumors less than 2 cm (p = 0.048). There was no difference in the detection of hypervascular HCCs between hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI (43/45: 96%) and dynamic MDCT (40/45: 89%), whereas the detection sensitivity of hypovascular tumors by Gd-EOB-DTPA-enhanced MRI was significantly higher than that by dynamic MDCT (39/41: 95% vs. 25/41: 61%, p = 0.001). EOB enhancement ratios were decreased in parallel with the degree of differentiation in DNs and HCCs, although there was no difference between DNs and hypovascular well-differentiated HCCs. The diagnostic ability of Gd-EOB-DTPA-enhanced MRI for hypervascular HCCs less than 2 cm was significantly higher than that of MDCT. For hypovascular tumors, the detection sensitivity of hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI was significantly higher than that of dynamic Gd-EOB-DTPA-enhanced MRI and dynamic MDCT. It was difficult to distinguish between DNs and hypovascular well-differentiated HCCs based on the EOB enhancement ratio.

  1. An Evaluation of the Chelating Agent EDDS for Marigold Production

    USDA-ARS?s Scientific Manuscript database

    Aminopolycarboxylic acid (APCA) ligands (chelating agents) like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are commonly used in soluble fertilizers to supply copper (Cu), iron (Fe), manganese (Mn), and/or zinc (Zn) to plants. The offsite runoff and contamina...

  2. Neurofibromas: location by scanning with Tc-99m DTPA. Work in progress

    SciTech Connect

    Mandell, G.A.; Herrick, W.C.; Harcke, H.T.; Sharkey, C.; Brooks, K.M.; MacEwen, G.D.

    1985-12-01

    The accumulation of technetium-99m diethylenetriamine pentaacetic acid (Tc-99m DTPA) in benign soft-tissue neurofibromatosis tumors is reported. In a series of 16 patients with clinical stigmata of neurofibromatosis, 28 sites of abnormal soft-tissue localization of the isotope observed scintigraphically were documented to be sites of soft-tissue tumor by clinical and/or radiographic (predominantly computed tomographic) correlations. The smallest lesion detected was a 1.5-cm subcutaneous neurofibroma. Normal physiologic nonrenal distribution of the Tc-99m DTPA was established by scintigraphic imaging of a control population.

  3. Thermodynamic stability and kinetic inertness of a Gd-DTPA bisamide complex grafted onto gold nanoparticles.

    PubMed

    Mogilireddy, Vijetha; Déchamps-Olivier, Isabelle; Alric, Christophe; Laurent, Gautier; Laurent, Sophie; Vander Elst, Luce; Muller, Robert; Bazzi, Rana; Roux, Stéphane; Tillement, Olivier; Chuburu, Françoise

    2015-01-01

    Gold nanoparticles coated by gadolinium (III) chelates (Au@DTDTPA) where DTDTPA is a dithiolated bisamide derivative of diethylenetriamine-N,N,N',N'',N''-pentaacetic acid (DTPA), constituted contrast agents for both X-ray computed tomography and magnetic resonance imaging. In an MRI context, highly stable Gd(3+) complexes are needed for in vivo applications. Thus, knowledge of the thermodynamic stability and kinetic inertness of these chelates, when grafted onto gold nanoparticles, is crucial since bisamide DTPA chelates are usually less suited for Gd(3+) coordination than DTPA. Therefore, these parameters were evaluated by means of potentiometric titrations and relaxivity measurements. The results showed that, when the chelates were grafted onto the nanoparticle, not only their thermodynamic stability but also their kinetic inertness were improved. These positive effects were correlated to the chelate packing at the nanoparticle surface that stabilized the corresponding Gd(3+) complexes and greatly enhanced their kinetic inertness.

  4. Complexation of DTPA and EDTA with Cd(2+): stability constants and thermodynamic parameters at the soil-water interface.

    PubMed

    Karak, Tanmoy; Paul, Ranjit Kumar; Das, Dilip Kumar; Boruah, Romesh Kumar

    2016-12-01

    Two alkaline soils collected from the surface horizon (0-15 cm) of two agricultural fields Lakshmikantapur (LKP; 22° 06' 03″ N and 88° 18' 19″ E) and Diamond Harbour (DHB; 22° 11' N and 88° 14' E) of West Bengal, India were studied to observe the stability of cadmium (Cd) chelate complexes with diethylenetriaminepentaacetatic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA), removing organic matter (OM). The objective of the present study is "determination of the stability constants and the thermodynamic parameters of Cd-DTPA and Cd-EDTA complexes at different pH and temperatures at the soil-water interface". Complex formation of soil Cd with DTPA and EDTA at the soil-water interface was studied under different ligand-to-metal ratios, pHs and temperatures. Apparent conditional stability constants (log k´) were calculated from the concentrations of Cd chelates and free Cd(2+), estimated by solid phase extraction with an ion exchanger. Standard Gibbs energy (ΔG°), standard enthalpy (ΔH°) and standard entropy (ΔS°) of formation were calculated at three different temperatures. The higher stability constants of Cd-DTPA than Cd-EDTA indicated longer persistence of Cd-DTPA at the soil solution interface than Cd-EDTA complex. Increase of ΔG°, ΔH° and ΔS° with progress of temperature revealed that Cd-complex formation was facilitated by temperature. Highly negative ΔG° and positive ΔH° for Cd-complex formation indicated the reaction spontaneous and exothermic. In general, both ligands complexed high percentages of cadmium signalling their role in enhancing remobilization of Cd present in soil and preventing exchange of contaminated Cd from external source with soil mineral matrix; these phenomena may greatly reduce hazard for environment and human health. The result of this study support that DTPA increases solubility and more persistence of Cd in acidic soils within the range of temperature and mole fraction (MF = moles of Cd(2+)

  5. Easy and efficient (111)indium labeling of long-term stored DTPA conjugated protein.

    PubMed

    Nalla, Amarnadh; Buch, Inge; Hesse, Birger

    2011-01-01

    The labelling efficiency of long-term stored DTPA-conjugates has not been reported previously even though DTPA has been in extensive use as metal chelator in the development of radiopharmaceuticals and contrast agents. DTPA is often used as a bifunctional chelating agent conjugated to tumor targeting vehicles such as monoclonal antibodies and receptor directed peptides. The purpose of this study was to monitor the labelling efficiency of a DTPA-conjugate on long-term storage using 111In-chloride at two different temperatures and incubation times for the In-labelling. Cyclic-diethylene-triamine-pentaacetic acid (cDTAP) was conjugated to a polyclonal immunoglobulin-G (IgG) in borate buffer, pH 8.2 at +4?C for 4 hours. Then the DTPA-conjugate was dialyzed against 50 mmol/l sodium citrate buffer saline, pH 6.0 and stored at -80° C in aliquots of 1 mg/0.5 ml. The DTPA-conjugate was labeled with 111In-chloride in citrate buffer, pH 6. The labelling reaction was incubated at room temperature (RT) for 30 min and at +4?C for 90 min. Determination of labelling efficiency was performed using ITLC and an instant chromatography scanner equipped with a NaI crystal. The labelling efficiency of the DTPA-conjugate was monitored every third month for 12 months. The median labelling efficiencies varied between 92 and 96% during the whole period. The two combinations of incubation times and temperatures (30 min at RT and 90 min at +4°C) had no affect on labelling efficiency of the DTPA-conjugate, stored for 12 months. Our study shows that 111In-labelling can easily be performed within 30 min at RT for thermo-stable proteins like polyclonal, DTPA-conjugated IgG stored long-term at -80°C with a high 111In-labelling efficiency.

  6. Computational analysis of the number, area and density of gamma-H2AX foci in breast cancer cells exposed to (111)In-DTPA-hEGF or gamma-rays using Image-J software.

    PubMed

    Cai, Zhongli; Vallis, Katherine A; Reilly, Raymond M

    2009-03-01

    To develop a simple method for the quantification of gamma-H2AX focus number, density and size. MDA-MB-468 human breast cancer cells were treated overnight with (111)In-diethylenetriaminepentaacetic acid human epidermal growth factor ((111)In-DTPA-hEGF, 0-142 kBq/pmol) or exposed to gamma-radiation to induce DNA double strand breaks (DSB). DNA DSB formation was evaluated by detection of phosphorylated histone H2AX on serine 139 (gamma-H2AX) using immunofluorescence. Confocal microscopy was used to capture images of gamma-H2AX foci and cell nuclei. Image-J software with customized macros was used to quantify gamma-H2AX foci. The number of gamma-H2AX foci per nucleus scored using Image-J correlated strongly with the number scored using direct visual confirmation (coefficient of determination, R(2) = 0.950; 60 nuclei scored). The mean density (grayscale values per pixel), area and integrated density (IntDen) of individual foci increased linearly as the specific radioactivity (SR) increased up to 67 kBq/pmol (R(2) values of 0.826, 0.964, 0.978, respectively). The mean number of foci per nucleus, the combined area of gamma-H2AX foci per nucleus and the IntDen per nucleus also increased linearly with SR, giving R(2) values of 0.926, 0.974 and 0.983, respectively. Similar linear relationships were observed with the gamma-ray absorbed dose up to 3.0 Gy. The density, area and IntDen of individual foci, as well as the number of gamma-H2AX foci, total focus area and IntDen per nucleus were successfully quantified using Image-J with customized macros.

  7. (68)Ga labeled fatty acids for cardiac metabolic imaging: Influence of different bifunctional chelators.

    PubMed

    Jain, Akanksha; Mathur, Anupam; Pandey, Usha; Sarma, Haladhar Dev; Dash, Ashutosh

    2016-12-01

    Development of (68)Ga labeled fatty acids is of immense interest due to the availability of (68)Ga through a generator and its superiority over SPECT based tracers in carrying out dynamic imaging on a PET scanner. Our present work explores the influence of different chelators on the cardiac uptake and pharmacokinetics of the (68)Ga-labeled fatty acids. Two new (68)Ga labeled fatty acids were synthesized by conjugation of 11-aminoundecanoic acid with the bifunctional chelators (BFCs) viz. p-SCN-Bn-DTPA (S-2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid) and p-SCN-Bn-NODAGA (S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1-glutaric acid-4,7-acetic acid) and their comparison was carried out with the previously reported (68)Ga-NOTA-undecanoic acid. Both the conjugates were radiolabeled with (68)Ga in high yields and purities (>95%). Their formation was established by preparation and characterization of their inactive analogs with (nat)Ga at macroscopic levels. Biodistribution studies of the complexes in Swiss mice showed lower initial myocardial uptake for (68)Ga-NODAGA-undecanoic acid (3.8±0.6%ID/g) and (68)Ga-DTPA-undecanoic acid (1.3±0.5%ID/g) complexes in comparison to previously reported (68)Ga-NOTA-undecanoic acid complex (7.4±2.8%ID/g) at 2min p.i. However, significant retention of the tracer in the myocardium was observed in the case of (68)Ga-NODAGA-undecanoic complex, which led to improved heart/non-target ratios of the complex over time in comparison to the other (68)Ga complexes. Similarly, the DTPA complex exhibited increased washout from the liver in comparison to other (68)Ga derivatives. The β oxidation mechanism in myocytes was investigated by isolating the myocardial extract post intravenous injection of the respective (68)Ga complexes and analyzing them by radio-HPLC, which showed metabolic transformation of the parent fatty acid complex peak in all the three complexes. This study has provided an insight into the design

  8. ( sup 111 In-DTPA-D-Phe sup 1 )-octreotide, a potential radiopharmaceutical for imaging of somatostatin receptor-positive tumors: Synthesis, radiolabeling and in vitro validation

    SciTech Connect

    Bakker, W.H.; Albert, R.; Bruns, C.; Breeman, W.A.P.; Hofland, L.J.; Marbach, P.; Pless, J.; Pralet, D.; Stolz, B.; Koper, J.W.; Lamberts, S.W.J.; Visser, T.J.; Krenning, E.P. Sandoz Pharma AG, Basel )

    1991-01-01

    As starting material for a potentially convenient radiopharmaceutical, a diethylenetriaminopentaacetic acid (DTPA) conjugated derivative of octreotide (SMS 201-995) was prepared. This peptide, (DTPA-D-Phe{sup 1})-octreotide (SDZ 215-811) binds more than 95% of added {sup 111}In in an easy, single-step labeling procedure without necessity of further purification. The specific somatostatin-like biologic effect of these analogues was proven by the inhibition of growth hormone secretion by cultured rat pituitary cells in a dose-dependent fashion by octreotide, (DTPA-D-Phe{sup 1})-octreotide and non-radioactive ({sup 115}In-DTPA-D-Phe{sup 1})-octreotide. The binding of ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide to rat brain cortex membranes proved to be displaced similarly by natural somatosatin as well as by octreotide, suggesting specific binding of ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide to somatostatin receptors. The binding of the indium-labeled compound showed a somewhat lower affinity when compared with the iodinated (Tyr{sup 3})-octreotide, but indium-labeled (DTPA-D-Phe{sup 1})-octreotide still binds with nanomolar affinity. In conjunction with in vivo studies, these results suggest that ({sup 111}In-DTPA-D-Phe{sup 1})-octreotide is a promising radiopharmaceutical for scintigraphic imaging of somatostatin receptor-positive tumors.

  9. Brain Delivery of Drug and MRI Contrast Agent: Detection and Quantitative Determination of Brain Deposition of CPT-Glu Using LC-MS/MS and Gd-DTPA Using Magnetic Resonance Imaging

    PubMed Central

    Tabanor, Kayann; Lee, Phil; Kiptoo, Paul; Choi, In-Young; Sherry, Erica B.; Eagle, Cheyenne Sun; Williams, Todd D.; Siahaan, Teruna J.

    2015-01-01

    Successful treatment and diagnosis of neurological diseases depend on reliable delivery of molecules across the blood-brain barrier (BBB), which restricts penetration of pharmaceutical drugs and diagnostic agents into the brain. Thus, developing new non-invasive strategies to improve drug delivery across the BBB is critically needed. This study was aimed at evaluating the activity of HAV6 peptide (Ac-SHAVSS-NH2) in improving brain delivery of camptothecin-glutamate (CPT-Glu) conjugate and gadolinium-diethylenetriaminepentaacetate (Gd-DTPA) contrast agent in Sprague-Dawley rats. Brain delivery of both CPT-Glu and Gd-DTPA was evaluated in an in situ rat brain perfusion model in the presence and absence of HAV6 peptide (1.0 mM). Gd-DTPA (0.6 mmol/kg) was intravenously (i.v.) administered with and without HAV6 peptide (0.019 mmol/kg) in rats. The detection and quantification of CPT-Glu and Gd-DTPA in the brain were carried out by LC-MS/MS and quantitative magnetic resonance imaging (MRI), respectively. Rats perfused with CPT-Glu in combination with HAV6 had significantly higher deposition of drug in the brain compared to CPT-Glu alone. MRI results also showed that administration of Gd-DTPA in the presence of HAV6 peptide led to significant accumulation of Gd-DTPA in various regions of the brain in both the in situ rat brain perfusion and in vivo studies. All observations taken together indicate that HAV6 peptide can disrupt the BBB and enhance delivery of small molecules into the brain. PMID:26705088

  10. Brain Delivery of Drug and MRI Contrast Agent: Detection and Quantitative Determination of Brain Deposition of CPT-Glu Using LC-MS/MS and Gd-DTPA Using Magnetic Resonance Imaging.

    PubMed

    Tabanor, Kayann; Lee, Phil; Kiptoo, Paul; Choi, In-Young; Sherry, Erica B; Eagle, Cheyenne Sun; Williams, Todd D; Siahaan, Teruna J

    2016-02-01

    Successful treatment and diagnosis of neurological diseases depend on reliable delivery of molecules across the blood-brain barrier (BBB), which restricts penetration of pharmaceutical drugs and diagnostic agents into the brain. Thus, developing new noninvasive strategies to improve drug delivery across the BBB is critically needed. This study was aimed at evaluating the activity of HAV6 peptide (Ac-SHAVSS-NH2) in improving brain delivery of camptothecin-glutamate (CPT-Glu) conjugate and gadolinium-diethylenetriaminepentaacetate (Gd-DTPA) contrast agent in Sprague-Dawley rats. Brain delivery of both CPT-Glu and Gd-DTPA was evaluated in an in situ rat brain perfusion model in the presence and absence of HAV6 peptide (1.0 mM). Gd-DTPA (0.6 mmol/kg) was intravenously (iv) administered with and without HAV6 peptide (0.019 mmol/kg) in rats. The detection and quantification of CPT-Glu and Gd-DTPA in the brain were carried out by LC-MS/MS and quantitative magnetic resonance imaging (MRI), respectively. Rats perfused with CPT-Glu in combination with HAV6 had significantly higher deposition of drug in the brain compared to CPT-Glu alone. MRI results also showed that administration of Gd-DTPA in the presence of HAV6 peptide led to significant accumulation of Gd-DTPA in various regions of the brain in both the in situ rat brain perfusion and in vivo studies. All observations taken together indicate that HAV6 peptide can disrupt the BBB and enhance delivery of small molecules into the brain.

  11. Environmentally relevant concentrations of aminopolycarboxylate chelating agents mobilize Cd from humic acid.

    PubMed

    North, Ashley E; Sarpong-Kumankomah, Sophia; Bellavie, Andrew R; White, Wade M; Gailer, Jürgen

    2017-07-01

    Although Cd is a pollutant of public health relevance, many dietary sources from which it can be absorbed into human tissues remain unknown. While it is well established that the biogeochemical cycle of Cd involves its complexation with environment-derived ligands (e.g., humic acids, HAs) and anthropogenic ones (e.g., chelating agents, CAs), the interaction of Cd with both of these ligands is less well understood. To gain insight, a HA-Cd complex was injected on a size-exclusion chromatography (SEC) column coupled on-line with a flame atomic absorption spectrometer (FAAS) using 10mmol/L Tris buffer (pH8.0) as the mobile phase. This approach allowed us to observe the intact HA-Cd complex and the retention behavior of Cd as a function of 2-20μmol/L concentrations of ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA) or methylglycinediacetic acid (MGDA) that were added to the mobile phase. An increase of the retention time of Cd was indicative of a partial or complete abstraction of Cd from HA. Our results revealed that all CAs abstracted Cd from the HA-Cd complex at concentrations of 5μmol/L, while MGDA and DTPA were effective at 2μmol/L. The bioavailability of some of the on-column formed CA-Cd complexes explains the previously reported increased accumulation of Cd in periphyton in the ecosystem downstream of wastewater treatment plants. In addition, our results imply that the use of effluents which contain CAs and Cd for the irrigation of food crops can introduce Cd into the food supply and compromise food safety. Copyright © 2017. Published by Elsevier B.V.

  12. COMBINING NEUTRAL AND ACIDIC EXTRACTANTS FOR RECOVERING TRANSURANIC ELEMENTS FROM NUCLEAR FUEL

    SciTech Connect

    Lumetta, Gregg J.; Neiner, Doinita; Sinkov, Sergey I.; Carter, Jennifer C.; Braley, Jenifer C.; Latesky, Stanley; Gelis, Artem V.; Tkac, Peter; Vandegrift, George F.

    2011-10-03

    We have been investigating a solvent extraction system that combines a neutral extractant--octyl(phenyl)-N,N-diisobutyl-carbamoylmethylphosphine oxide (CMPO)--with an acidic extractant--bis(2-ethylhexyl)phosphoric acid (HDEHP)--to form a single process solvent for separating Am and Cm from the other components of irradiated nuclear fuel. It was originally hypothesized that the extraction chemistry of CMPO would dominate under conditions of high acidity (> 1 M HNO3), resulting in co-extraction of the transuranic and lanthanide elements into the organic phase. Contacting the loaded solvent with a solution of diethylenetriaminepentaacetate (DTPA) buffered with lactic or citric acid at pH {approx}3 to 4 would result in a condition in which the HDEHP chemistry dominates. Although the data somewhat support this hypothesis, it is clear that there are interactions between the two extractants such that they do not act independently in the extraction and stripping regimes. We report here studies directed at determining the nature and extent of interaction between CMPO and HDEHP, the synergistic behavior of CMPO and HDEHP in the extraction of americium and neodymium, and progress towards determining the thermodynamics of this extraction system. Neodymium and americium behave similarly in the combined solvent system, with a significant synergy between CMPO and HDEHP in the extraction of both of these trivalent elements from lactate-buffered DTPA solutions. In contrast, a much weaker synergistic behaviour is observed for europium. Thus, investigations into the fundamental chemistry involved in this system have focused on the neodymium extraction. The extraction of neodymium has been systematically investigated, individually varying the HDEHP concentration, the CMPO concentration, or the aqueous phase composition. Thermodynamic modeling of the neodymium extraction system has been initiated. Interactions between CMPO and HDEHP in the organic phase must be taken into account in

  13. Heavy metal uptake and leaching from polluted soil using permeable barrier in DTPA-assisted phytoextraction.

    PubMed

    Zhao, Shulan; Shen, Zhiping; Duo, Lian

    2015-04-01

    Application of sewage sludge (SS) in agriculture is an alternative technique of disposing this waste. But unreasonable application of SS leads to excessive accumulation of heavy metals in soils. A column experiment was conducted to test the availability of heavy metals to Lolium perenne grown in SS-treated soils following diethylene triamine penta acetic acid (DTPA) application at rates of 0, 10 and 20 mmol kg(-1) soil. In order to prevent metal leaching in DTPA-assisted phytoextraction process, a horizontal permeable barrier was placed below the treated soil, and its effectiveness was also assessed. Results showed that DTPA addition significantly increased metal uptake by L. perenne shoots and metal leaching. Permeable barriers increased metal concentrations in plant shoots and effectively decreased metal leaching from the treated soil. Heavy metals in SS-treated soils could be gradually removed by harvesting L. perenne many times in 1 year and adding low dosage of DTPA days before each harvest.

  14. Biodistribution of Ru-97-labeled DTPA, DMSA and transferrin. [Diagnostic potential

    SciTech Connect

    Som, P; Oster, Z H; Fairchild, R G; Atkins, H L; Brill, A B; Gil, M C; Srivastava, S C; Meinken, G E; Goldman, A G; Richards, P

    1980-01-01

    Ruthenium-97 is being produced at the Brookhaven Linac Isotope Producer (BLIP). The favorable physical properties of Ru-97 and chemical reactivity of ruthenium offer a potential for using this isotope to label compounds useful for delayed scanning. Diethylenetriamine pentaacetic acid (DTPA), 2,3-Dimercaptosuccinic acid (DMSA), and Transferrin (TF) were labeled with Ru-97-chloride. Ru-97-DTPA and In-111-DTPA, injected intravenously, showed similar organ distribution, kinetics, and more than 80% excretion by 0.5 h. Ru-97-DTPA and In-111-DTPA injected into the cisterna magna of dogs showed similar kinetics in brain, blood, and urinary bladder. The energy deposited by 1 mCi In-111-DTPA is twice that from 1 mCi Ru-97-DTPA. High quality camera images of the CSF space in the dog were obtained with both isotopes. Ru-97-DMSA was prepared with and without the addition of SnCl/sub 2/.2H/sub 2/O. Tin-free DMSA was rapidly excreted via the kidneys, whereas for maximum cortical deposition, the tin-containing preparation was superior. This compound is suitable for delayed imaging of both normal and impaired kidneys. Tissue distribution studies were performed in abscess-bearing rats with Ru-97-transferrin. Although blood levels were higher than with Ga-67-citrate, the abscess had twice as much Ru-97-TF as Ga-67-citrate and the Ru-97 muscle activity was one-third that of Ga-67. Imaging of abscess-bearing rabbits with Ru-97-TF visualized the abscesses as early as 1/2 hr after injection. Since the initial images visualize the abscess so clearly and since the TF portion of the compound binds to the abscess, Tc-99m-TF is being studied for the same purpose. Ru-97-labeled compounds are a promising replacement for In-111 and possibly also for Ga-67 compounds with the advantages of lower radiation dose and high quality image. (ERB)

  15. Magnetic Resonance Imaging of Acute Reperfused Myocardial Infarction: Intraindividual Comparison of ECIII-60 and Gd-DTPA in a Swine Model

    SciTech Connect

    Jin Jiyang; Teng Gaojun; Feng Yi; Wu Yanping; Jin Qindi; Wang Yu; Wang Zhen; Lu Qin; Jiang Yibo; Wang Shengqi; Chen Feng; Marchal, Guy; Ni Yicheng

    2007-04-15

    Purpose. To compare a necrosis-avid contrast agent (NACA) bis-Gd-DTPA-pamoic acid derivative (ECIII-60) after intracoronary delivery with an extracellular agent Gd-DTPA after intravenous injection on magnetic resonance imaging (MRI) in a swine model of acute reperfused myocardial infarction (MI). Methods. Eight pigs underwent 90 min of transcatheter coronary balloon occlusion and 60 min of reperfusion. After intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg, all pigs were scanned with T1-weighted MRI until the delayed enhancement of MI disappeared. Then they were intracoronarily infused with ECIII-60 at 0.0025 mmol/kg and imaged for 5 hr. Signal intensity, infarct-over-normal contrast ratio and relative infarct size were quantified, compared, and correlated with the results of postmortem MRI and triphenyltetrazolium chloride (TTC) histochemical staining. Results. A contrast ratio over 3.0 was induced by both Gd-DTPA and ECIII-60. However, while the delayed enhancement with Gd-DTPA virtually vanished in 1 hr, ECIII-60 at an 80x smaller dose depicted the MI accurately over 5 hr as proven by ex vivo MRI and TTC staining. Conclusion. Both Gd-DTPA and ECIII-60 strongly enhanced acute MI. Comparing with fading contrast in a narrow time window with intravenous Gd-DTPA, intracoronary ECIII-60 persistently demarcated the acute MI, indicating a potential method for postprocedural assessment of myocardial viability after coronary interventions.

  16. Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA

    NASA Astrophysics Data System (ADS)

    Mroue, Kamal H.; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H.; Morris, Michael D.; Ramamoorthy, Ayyalusamy

    2014-07-01

    Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA = Diethylene triamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the 1H T1 values were calculated from data collected by 1H spin-inversion recovery method detected in natural-abundance 13C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the 1H T1 values can be successfully reduced by a factor of 3.5 using as low as 10 mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the 13C CPMAS spectra. These results obtained from 13C-detected CPMAS experiments were further confirmed using 1H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans.

  17. Scavenging of free-radical metabolites of aniline xenobiotics and drugs by amino acid derivatives: toxicological implications of radical-transfer reactions.

    PubMed

    Michail, Karim; Baghdasarian, Argishti; Narwaley, Malyaj; Aljuhani, Naif; Siraki, Arno G

    2013-12-16

    We investigated a novel scavenging mechanism of arylamine free radicals by poly- and monoaminocarboxylates. Free radicals of arylamine xenobiotics and drugs did not react with oxygen in peroxidase-catalyzed reactions; however, they showed marked oxygen uptake in the presence of an aminocarboxylate. These free-radical intermediates were identified using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and electron paramagnetic resonance (EPR) spectrometry. Diethylenetriaminepentaacetic acid (DTPA), a polyaminocarboxylate, caused a concentration-dependent attenuation of N-centered radicals produced by the peroxidative metabolism of arylamines with the subsequent formation of secondary aliphatic carbon-centered radicals stemming from the cosubstrate molecule. Analogously, N,N-dimethylglycine (DMG) and N-methyliminodiacetate (MIDA), but not iminodiacetic acid (IDA), demonstrated a similar scavenging effect of arylamine-derived free radicals in a horseradish peroxidase/H2O2 system. Using human promyelocytic leukemia (HL-60) cell lysate as a model of human neutrophils, DTPA, MIDA, and DMG readily reduced anilinium cation radicals derived from the arylamines and gave rise to the corresponding carbon radicals. The rate of peroxidase-triggered polymerization of aniline was studied as a measure of nitrogen-radical scavenging. Although, IDA had no effect on the rate of aniline polymerization, this was almost nullified in the presence of DTPA and MIDA at half of the molar concentration of the aniline substrate, whereas a 20 molar excess of DMPO caused only a partial inhibition. Furthermore, the yield of formaldehyde, a specific reaction endproduct of the oxidation of aminocarboxylates by aniline free-radical metabolites, was quantitatively determined. Azobenzene, a specific reaction product of peroxidase-catalyzed free-radical dimerization of aniline, was fully abrogated in the presence of DTPA, as confirmed by GC/MS. Under aerobic conditions, a radical-transfer reaction

  18. A systematic study on the utility of CHX-A''-DTPA-NCS and NOTA-NCS as bifunctional chelators for (177)Lu radiopharmaceuticals.

    PubMed

    Pandey, Usha; Gamre, Naresh; Lohar, Sharad Pandurang; Dash, Ashutosh

    2017-09-01

    This paper describes the evaluation of [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA-NCS) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) as bifunctional chelators for (177)Lu. While (177)Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of (177)Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of (177)Lu-NOTA-NCS significantly as compared to (177)Lu-CHX-A''-DTPA-NCS. In vitro stability of (177)Lu-CHX-A''-DTPA-NCS was also superior to (177)Lu-NOTA-NCS. It could be concluded from this study that among the two chelators evaluated, CHX-A''-DTPA-NCS is more appropriate for preparation of (177)Lu radiopharmaceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Plutonium-DTPA Model Application with USTUR Case 0269.

    PubMed

    Konzen, Kevin; Brey, Richard; Miller, Scott

    2016-01-01

    A plutonium-DTPA (Pu-DTPA) biokinetic model was introduced that had originated from the study of a plutonium-contaminated wound. This work evaluated the extension of the Pu-DTPA model to United States Transuranium and Uranium Registry (USTUR) Case 0269 involving an acute inhalation of a plutonium nitrate aerosol. Chelation was administered intermittently for the first 7 mo as Ca-EDTA, mostly through intravenous injection, with Ca-DTPA treatments administered approximately 2.5 y post intake. Urine and fecal bioassays were collected following intake for several years. Tissues were collected and analyzed for plutonium content approximately 38 y post intake. This work employed the Pu-DTPA model for predicting the urine and fecal bioassay and final tissue quantity at autopsy. The Pu-DTPA model was integrated with two separate plutonium systemic models (i.e., ICRP Publication 67 and its proposed modification). This work illustrated that the Pu-DTPA model was useful for predicting urine and fecal bioassay, including final tissue quantity, 38 y post intake.

  20. Kinetics of formation for lanthanide (III) complexes of DTPA-(Me-Trp)2 used as imaging agent.

    PubMed

    Tiwari, Anjani K; Sinha, Deepa; Datta, Anupama; Kakkar, Dipti; Mishra, Anil K

    2011-05-01

    Diethlenetriamine-N,N,N'N''N''-pentaacetic acid (DTPA)-bis (amide) analogs have been synthesized and evaluated as a potential biomedical imaging agents. Imaging and biodistribution studies were performed in mice that showed a significant accumulation of DTPA analogs in brain. The stability and protonation constants of the complexes formed between the ligand [DTPA-(Me-Trp)(2)] and Gd(3+), Eu(3+), and Cu(2+) have been determined by pH potentiometry (Gd(3+), Eu(3+)) and spectrophotometry (Cu(2+)) at 25 °C and at constant ionic strength maintained by 0.10 M KCl. The kinetic inertness of Gd [DTPA-(Me-Trp)(2)] was characterized by the rates of exchange reactions with Zn(2+) and Eu(3+). In the Eu(3+) exchange, a second-order [H(+)] dependence was found for the pseudo-first-order rate constant [k(0) = (4.5 ± 1.2) × 10(-6)/s; k(1) = 0.58 ± 0.1 /M/s, k(2) = (6.6 ± 0.2) × 10(4) /M(2)/s, k(3) = (4.8 ± 0.8) × 10(-4) /M/s]. In the Eu(3+) exchange, at pH <5.0, the rate decreases with increasing concentration of the exchanging ion. At physiological pH, the kinetic inertness of [DTPA-(Me-Trp)(2)] is more inert than GdDTPA(2-), the most commonly used MRI contrast agent (t(1/2) = 127 h). High kinetic stability is an important requirement for the Gd complexes used as contrast enhancement agents in magnetic resonance imaging. © 2011 John Wiley & Sons A/S.

  1. Coupling Gd-DTPA with a bispecific, recombinant protein anti-EGFR-iRGD complex improves tumor targeting in MRI

    PubMed Central

    XIN, XIAOYAN; SHA, HUIZI; SHEN, JINGTAO; ZHANG, BING; ZHU, BIN; LIU, BAORUI

    2016-01-01

    Recombinant anti-epidermal growth factor receptor-internalizing arginine-glycine-aspartic acid (anti-EGFR single-domain antibody fused with iRGD peptide) protein efficiently targets the EGFR extracellular domain and integrin αvβ/β5, and shows a high penetration into cells. Thus, this protein may improve penetration of conjugated drugs into the deep zone of gastric cancer multicellular 3D spheroids. In the present study, a novel tumor-targeting contrast agent for magnetic resonance imaging (MRI) was developed, by coupling gadolinium-diethylene triamine pentaacetate (Gd-DTPA) with the bispecific recombinant anti-EGFR-iRGD protein. The anti-EGFR-iRGD protein was extracted from Escherichia coli and Gd was loaded onto the recombinant protein by chelation using DTPA anhydride. Single-targeting agent anti-EGFR-DTPA-Gd, which served as the control, was also prepared. The results of the present study showed that anti-EGFR-iRGD-DTPA-Gd exhibited no significant cyto toxicity to human gastric carcinoma cells (BGC-823) under the experimental conditions used. Compared with a conventional contrast agent (Magnevist), anti-EGFR-iRGD-DTPA-Gd showed higher T1 relaxivity (10.157/mM/sec at 3T) and better tumor-targeting ability. In addition, the signal intensity and the area under curve for the enhanced signal time in tumor, in vivo, were stronger than Gd-DTPA alone or the anti-EGFR-Gd control. Thus, Gd-labelled anti-EGFR-iRGD has potential as a tumor-targeting contrast agent for improved MRI. PMID:27035336

  2. Permeability of ferret trachea in vitro to {sup 99m}{Tc}-DTPA and [{sup 14}C]antipyrine

    SciTech Connect

    Hanafi, Z.; Webber, S.E.; Widdicombe, J.G.

    1994-09-01

    Platelet-activating factor (PAF) and vasoactive drugs were tested on permeability of ferret trachea in vitro by measuring fluxes of {sup 99m}{Tc}-diethylenetriamine pentaacetic acid ({sup 99m}{Tc}-DTPA; hydrophilic) and [{sup 14}C]antipyrine ([{sup 14}C]AP; lipophilic) across the tracheal wall. Tracheae were bathed on both sides with Krebs-Henseleit buffer, with luminal buffer containing either {sup 99m}{Tc}-DTPA or [{sup 14}C]AP. Luminal and abluminal radioactivities, potential difference, and tracheal smooth muscle tone were measured. Baseline {sup 99m}{Tc}-DTPA and [{sup 14}C]AP permeability coefficients were - 4.7 {+-} 0.6 (SE) x 10{sup {minus}7} and -2.2 {+-} 0.1 x 10{sup {minus}5} cm/s, respectively. PAF (10 {mu}M) increased permeability to {sup 99m}{Tc}-DTPA to -35.3 {+-} 7.6 x 10{sup {minus}7} cm/s (P < 0.05), but permeability to [{sup 14}C]AP did not change, suggesting that paracellular but not transcellular transport was affected. Abluminal and luminal applications of methacholine (MCh, 20 {mu}M), phenylephrine (PE, 100 {mu}M), and albuterol (Alb, 100 {mu}M) caused no change in permeability to {sup 99m}{Tc}-DTPA before or after exposure to luminal PAF, but abluminal histamine (Hist, 10 {mu}M) significantly increased permeability. Abluminal Hist decreased permeability to [{sup 14}C]AP before and after exposure to PAF. MCh, PE, and Hist increased smooth muscle tone; Alb and PAF had no effect. Thus, only PAF and Hist altered permeability to {sup 99m}{Tc}-DTPA, and MCh, PE, and Hist changed smooth muscle tone. Tracheal permeability changes were greater for the hydrophilic than for the lipophilic agent. 37 refs., 11 figs., 1 tab.

  3. Photo-cured PMMA/PEI core/shell nanoparticles surface-modified with Gd-DTPA for T1 MR imaging.

    PubMed

    Ratanajanchai, Montri; Lee, Don Haeng; Sunintaboon, Panya; Yang, Su-Geun

    2014-02-01

    Herein, we introduced amine-functionalized core-shell nanoparticles (Polymethyl methacrylate/Polyethyleneimine; PMMA/PEI) with surface primary amines (3.15×10(5) groups/particle) and uniform size distribution (150-200nm) that were prepared by one-step photo-induced emulsion polymerization. Further PEI-surface was modified with diethylenetriamine pentaacetic acid (DTPA) and introduced with Gd(III). The modified particles possessing DTPA can entrap a high content of Gd(III) ions of over 5.5×10(4)Gd/particle with stable chelation (no release of free Gd) at least 7h. The Gd-DTPA-conjugated core-shell nanoparticles (PMMA/PEI-DTPA-Gd NPs) enhanced the MRI intensity more than Primovist (a commercial hepatic contrast agent). Moreover, the PMMA/PEI-DTPA-Gd NPs showed non-cytotoxicity up to 250μM in normal liver cells. Thus, in vitro data suggested the PMMA/PEI-DTPA-Gd NPs is promising delivery system as a superior MRI contrast agent, especially for hepatic lesion targeted MR imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Contrast agent Gd-EOB-DTPA (EOB·Primovist®) for low-field magnetic resonance imaging of canine focal liver lesions.

    PubMed

    Yonetomi, Daisuke; Kadosawa, Tsuyoshi; Miyoshi, Kenjirou; Nakao, Yukie; Homma, Emi; Hanazono, Kiwamu; Yamada, Eriko; Nakamura, Kozo; Ijiri, Atsuki; Minegishi, Noriyuki; Maetani, Shigeki; Hirayama, Kazuko; Taniyama, Hiroyuki; Nakade, Tetsuya

    2012-01-01

    Contrast-enhanced magnetic resonance (MR) imaging with a new liver-specific contrast agent gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA; EOB·Primovist®) was studied in 14 normal beagles and 9 dogs with focal liver lesions. Gd-EOB-DTPA accumulates in normally functioning hepatocytes 20 min after injection. As with Gd-DTPA, it is also possible to perform a dynamic multiphasic examination of the liver with Gd-EOB-DTPA, including an arterial phase and a portal venous phase. First, a reliable protocol was developed and the appropriate timings for the dynamic study and the parenchymal phase in normal dogs using Gd-EOB-DTPA were determined. Second, the patterns of these images were evaluated in patient dogs with hepatic masses. The optimal time of arterial imaging was from 15 s after injection, and the optimal time for portal venous imaging was from 40 s after injection. Meanwhile, the optimal time to observe changes during the hepatobiliary phase was from 20 min after injection. In patient dogs, 11 lesions were diagnosed as malignant tumors; all were hypointense to the surrounding normal liver parenchyma during the hepatobiliary phase. Even with a low-field MR imaging unit, the sequences afforded images adequate to visualize the liver parenchyma and to detect tumors within an appropriate scan time. Contrast-enhanced MR imaging with Gd-EOB-DTPA provides good demarcation on low-field MR imaging for diagnosing canine focal liver lesions.

  5. Rapid and reversible enhancement of blood–brain barrier permeability using lysophosphatidic acid

    PubMed Central

    On, Ngoc H; Savant, Sanjot; Toews, Myron; Miller, Donald W

    2013-01-01

    The present study characterizes the effects of lysophosphatidic acid (LPA) on blood–brain barrier (BBB) permeability focusing specifically on the time of onset, duration, and magnitude of LPA-induced changes in cerebrovascular permeability in the mouse using both magnetic resonance imaging (MRI) and near infrared fluorescence imaging (NIFR). Furthermore, potential application of LPA for enhanced drug delivery to the brain was also examined by measuring the brain accumulation of radiolabeled methotrexate. Exposure of primary cultured brain microvessel endothelial cells (BMECs) to LPA produced concentration-dependent increases in permeability that were completely abolished by clostridium toxin B. Administration of LPA disrupted BBB integrity and enhanced the permeability of small molecular weight marker gadolinium diethylenetriaminepentaacetate (Gd-DTPA) contrast agent, the large molecular weight permeability marker, IRdye800cwPEG, and the P-glycoprotein efflux transporter probe, Rhodamine 800 (R800). The increase in BBB permeability occurred within 3 minutes after LPA injection and barrier integrity was restored within 20 minutes. A decreased response to LPA on large macromolecule BBB permeability was observed after repeated administration. The administration of LPA also resulted in 20-fold enhancement of radiolabeled methotrexate in the brain. These studies indicate that administration of LPA in combination with therapeutic agents may increase drug delivery to the brain. PMID:24045401

  6. Synthesis and characterization of a novel chemically designed (Globo)3-DTPA-KLH antigen.

    PubMed

    Hajmohammadi, Mehdi; Siadat, Seyed Davar; Ghorbani, Masoud; Shafiee Ardestani, Mehdi; Teimourian, Shahram; Asgari, Vahid; Ahangari Cohan, Reza; Hajmohammadi, Mostafa; Hajmohammadi, Akram; Behzadi, Ramezan; Rajab Nezhad, Saied; Namvar Asl, Nabiollah

    2015-01-01

    In recent years, many experiments have been conducted for the production and evaluation of anticancer glycoconjugated vaccines in developed countries and many achievements have been accomplished with Globo H derivatives. In the current experiment, a new chemically designed triplicate version of (Globo H)3-diethylenetriamine pentaacetic acid (DTPA)-KLH antigen was synthesized and characterized. Immunization with (Globo H)3-DTPA-KLH, a hexasaccharide that is a member of a family of antigenic carbohydrates that are highly expressed in various types of cancers conjugated with DTPA and KLH protein, induced a high level of antibody titer along with an elevated level of IL-4 in mice. Treatment of tumors with the collected sera from immunized mice decreased the tumor size in nude mice as well. None of the immunized mice illustrated any sign of tumor growth after injection of MCF-7 cells compared to the control animals. These findings, based on the newly presented structure of the Globo H antigen, lend exciting and promising evidence for clinical advancement in the development of a therapeutic vaccine in the future.

  7. MR imaging of the cochlear modiolus after intratympanic administration of Gd-DTPA.

    PubMed

    Kawai, Hisashi; Naganawa, Shinji; Ishihara, Shunichi; Sone, Michihiko; Nakashima, Tsutomu

    2010-01-01

    We evaluated whether enhancement of the cochlear modiolus could be visualized 24 hours after intratympanic injection of gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) using a 3-dimensional real inversion recovery sequence combined with a 32-channel head coil at 3 tesla. Intratympanic injection of Gd-DTPA has been reported for visualizing endolymphatic hydrops in Meniere's disease, and its use has shown communication between the cochlear perilymph and cerebrospinal fluid in the internal auditory canal. Although the cochlear modiolus has been considered the route for this communication, this has not been confirmed through direct visualization of its enhancement. We qualitatively and quantitatively evaluated the presence of contrast enhancement in the modiolus in 19 patients with clinically suspected endolymphatic hydrops or hearing loss who underwent imaging as described above. The contrast ratio (CR) between the cochlear modiolus and cerebellar white matter on the injected side was 1.09+/-1.23, and that on the non-injected side was -0.48+/-0.38 (P<0.01). In all subjects, the CR value was larger on the injected than non-injected side, and enhancement of the cochlear modiolus was also recognized visually. Intratympanic Gd-DTPA can be administered to visualize enhancement of the cochlear modiolus and may thereby reveal its functional anatomy.

  8. DTPA aerosol in ventilation/perfusion scintigraphy for diagnosing pulmonary embolism.

    PubMed

    Trujillo, N P; Pratt, J P; Talusani, S; Quaife, R A; Kumpe, D; Lear, J L

    1997-11-01

    The use of lung scintigraphy in evaluating suspected pulmonary embolism (PE) is controversial. Several diagnostic methods have been described for lung scans, of which the most widely applied uses 99mTc-MAA for perfusion, 133Xe for ventilation and PIOPED diagnostic criteria. This study evaluates the accuracy of lung scintigraphy using an alternative ventilation agent, 99mTc-diethylenetriamine pentacetic acid (DTPA) aerosol, and specific criteria. Diagnostic criteria for DTPA aerosol ventilation were prospectively applied to 5017 patients over a 9-yr period. Lung scan interpretations were analyzed for frequency of occurrence, and results were compared to those of angiography in 455 patients. Scans were interpreted as normal, low or high probability in 79% of patients and as either indeterminate or medium probability in 21% of patients. Three patients had normal scans and negative angiography. In patients with low-probability scans, 111 angiograms were performed: 103 (93%) were negative, and 8 (7%) were positive. In patients with indeterminate scans, 114 angiograms were performed: 85 (75%) were negative, and 29 (25%) were positive. In patients with medium-probability scans, 149 angiograms were performed: 86 (58%) were negative, and 63 (42%) were positive. In patients with high-probability scans, 78 angiograms were performed: 6 (8%) were negative, and 72 (92%) were positive. These results indicate that lung scintigraphy using DTPA aerosol and our criteria is accurate in diagnosing and stratifying risk of pulmonary embolic disease. Compared with 133Xe and PIOPED criteria, DTPA ventilation and our criteria reduced the false-negative rate in low-probability scans (7% versus 16%, p < 0.005) and decreased the fraction of intermediate-probability scans (21 % versus 39%, p < 0.01).

  9. Development of the Plutonium-DTPA Biokinetic Model.

    PubMed

    Konzen, Kevin; Brey, Richard

    2015-06-01

    Estimating radionuclide intakes from bioassays following chelation treatment presents a challenge to the dosimetrist due to the observed excretion enhancement of the particular radionuclide of concern where no standard biokinetic model exists. This document provides a Pu-DTPA biokinetic model that may be used for making such determination for plutonium intakes. The Pu-DTPA biokinetic model is intended to supplement the standard recommended biokinetic models. The model was used to evaluate several chelation strategies that resulted in providing recommendations for effective treatment. These recommendations supported early treatment for soluble particle inhalations and an initial 3-day series of DTPA treatments for wounds. Several late chelation strategies were also compared where reduced treatment frequencies proved to be as effective as multiple treatments. The Pu-DTPA biokinetic model can be used to assist in estimating initial intakes of transuranic radionuclides and for studying the effects of different treatment strategies.

  10. Development of the Plutonium-DTPA biokinetic model

    DOE PAGES

    Konzen, Kevin; Brey, Richard

    2015-06-01

    Estimating radionuclide intakes from bioassays following chelation treatment presents a challenge to the dosimetrist due to the observed excretion enhancement of the particular radionuclide of concern, where no standard biokinetic model exists. This document provides a Pu-DTPA biokinetic model that may be used for making such determination for plutonium intakes. The Pu-DTPA biokinetic model is intended to supplement the standard recommended biokinetic models. The model was used to evaluate several chelation strategies that resulted in providing recommendations for effective treatment. These recommendations supported early treatment for soluble particle inhalations and an initial 3-day treatment series of DTPA treatments for wounds.more » Several late chelation strategies were also compared where reduced treatment frequencies proved to be as effective as multiple treatments. Furthermore, the Pu-DTPA biokinetic model can be used to assist in estimating initial intakes of transuranic radionuclides, and for studying the effects of different treatment strategies.« less

  11. Development of the Plutonium-DTPA biokinetic model

    SciTech Connect

    Konzen, Kevin; Brey, Richard

    2015-06-01

    Estimating radionuclide intakes from bioassays following chelation treatment presents a challenge to the dosimetrist due to the observed excretion enhancement of the particular radionuclide of concern, where no standard biokinetic model exists. This document provides a Pu-DTPA biokinetic model that may be used for making such determination for plutonium intakes. The Pu-DTPA biokinetic model is intended to supplement the standard recommended biokinetic models. The model was used to evaluate several chelation strategies that resulted in providing recommendations for effective treatment. These recommendations supported early treatment for soluble particle inhalations and an initial 3-day treatment series of DTPA treatments for wounds. Several late chelation strategies were also compared where reduced treatment frequencies proved to be as effective as multiple treatments. Furthermore, the Pu-DTPA biokinetic model can be used to assist in estimating initial intakes of transuranic radionuclides, and for studying the effects of different treatment strategies.

  12. Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?

    PubMed

    Le Du, Alicia; Sabatié-Gogova, Andrea; Morgenstern, Alfred; Montavon, Gilles

    2012-04-01

    The interaction between thorium and human serum components was studied using difference ultraviolet spectroscopy (DUS), ultrafiltration and high-pressure-anion exchange chromatography (HPAEC) with external inductively conducted plasma mass spectrometry (ICP-MS) analysis. Experimental data are compared with modelling results based on the law of mass action. Human serum transferrin (HSTF) interacts strongly with Th(IV), forming a ternary complex including two synergistic carbonate anions. This complex governs Th(IV) speciation under blood serum conditions. Considering the generally used Langmuir-type model, values of 10(33.5) and 10(32.5) were obtained for strong and weak sites, respectively. We showed that trace amounts of diethylene triamine pentaacetic acid (DTPA) cannot complex Th(IV) in the blood serum at equilibrium. Unexpectedly this effect is not related to the competition with HSTF but is due to the strong competition with major divalent metal ions for DTPA. However, Th-DTPA complex was shown to be stable for a few hours when it is formed before addition in the biological medium; this is related to the high kinetic stability of the complex. This makes DTPA a potential chelating agent for synthesis of (226)Th-labelled biomolecules for application in targeted alpha therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Potential Role of Tc-99m DTPA Diuretic Renal Scan in the Diagnosis of Calyceal Diverticulum in Children

    PubMed Central

    Lin, Chun-Chen; Shih, Bing-Fu; Shih, Shin-Lin; Tsai, Jeng-Daw

    2015-01-01

    Abstract The aim of the study was to assess the usefulness of Technetium-99m diethylene triamine pentaacetic acid (Tc-99m DTPA) diuretic scan to diagnose calyceal diverticulum (CD). From January 2000 to June 2014, children with evidence of renal cystic lesions of undetermined diagnosis on ultrasound were enrolled. Computed tomography urography (CTU) and Tc-99m DTPA diuretic scan were performed to characterize the precise anatomy. The diagnosis of CD depended on visualization of a renal cystic lesion with filling of contrast material or radiotracer from the collecting system on CTU or diuretic renal scan. Children who had positive findings of CD on 1 or both imaging studies were selected and analyzed. Both CTU and Tc-99m DTPA diuretic renal scan were performed in 39 children. A total of 9 (23.1 %) children with CD were diagnosed. All 9 children had positive diagnosis of CD on diuretic renal scan. Only 6 (66.7%) children could be diagnosed by CTU, and CD was missed by CTU in 3 subjects. The differential renal functions in patients with CD were 46% to 55%. The time of radiotracer appearance in the CD ranged from the 8th to the 24th minute. Seven patients had persistent accumulation of radiotracer in their CD at the end of the study. Tc-99m DTPA diuretic renal scan seems to be more sensitive than CTU in diagnosing CD. The possible reasons of higher sensitivity are discussed. Additional advantages that Tc-99m DTPA diuretic renal scan provides include the following: continuous monitoring, less radiation doses, and information on renal function, making it an attractive alternative to CTU for diagnosis of CD. PMID:26091475

  14. The efficiency of Gd-EOB-DTPA-enhanced magnetic resonance cholangiography in living donor liver transplantation: a preliminary study.

    PubMed

    Ogul, Hayri; Kantarci, Mecit; Pirimoglu, Berhan; Karaca, Leyla; Aydinli, Bulent; Okur, Aylin; Ozturk, Gurkan; Kizrak, Yesim

    2014-03-01

    The aim of this study was to evaluate utility of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiography (MRC) for the detection of biliary complications after living donor liver transplantation (LDLT). A total of 18 patients with suspected biliary complications underwent MRC. T2-weighted MRC and contrast-enhanced MRC (CE-MRC) were used to identify the biliary complications. MRC included routine breath-hold T2-weighted MRC using half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences and Gd-EOB-DTPA-enhanced MRC T1-weighted volumetric interpolated breath-hold examination (VIBE) sequences. Before confirming the biliary complications, one observer reviewed the MRC images and the CE-MRC images separately. The verification procedures and MRC findings were compared, and the sensitivity, specificity, and accuracy of both techniques were calculated for the identification of biliary complications. The observer found six of seven biliary complications using CE-MRC. The sensitivity was 85.7% and the accuracy was 94.4%. Using MRC alone, sensitivity was 57.1% and accuracy was 55.5%. The accuracy of Gd-EOB-DTPA-enhanced MRC was superior to MRC in locating biliary leaks (p < 0.05). The usage of Gd-EOB-DTPA-enhanced MRC yields information that complements the MRC findings that improve the identification of biliary complications. We recommend the use of MRC in addition to Gd-EOB-DTPA-enhanced MRC to increase the preoperative accuracy when assessing the biliary complications after LDLT.

  15. Improved labelling of DTPA- and DOTA-conjugated peptides and antibodies with 111In in HEPES and MES buffer.

    PubMed

    Brom, Maarten; Joosten, Lieke; Oyen, Wim Jg; Gotthardt, Martin; Boerman, Otto C

    2012-01-27

    In single photon emission computed tomography [SPECT], high specific activity of 111In-labelled tracers will allow administration of low amounts of tracer to prevent receptor saturation and/or side effects. To increase the specific activity, we studied the effect of the buffer used during the labelling procedure: NaAc, NH4Ac, HEPES and MES buffer. The effect of the ageing of the 111InCl3 stock and cadmium contamination, the decay product of 111In, was also examined in these buffers. Escalating amounts of 111InCl3 were added to 1 μg of the diethylene triamine pentaacetic acid [DTPA]- and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA]-conjugated compounds (exendin-3, octreotide and anti-carbonic anhydrase IX [CAIX] antibody). Five volumes of 2-(N-morpholino)ethanesulfonic acid [MES], 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid [HEPES], NH4Ac or NaAc (0.1 M, pH 5.5) were added. After 20 min at 20°C (DTPA-conjugated compounds), at 95°C (DOTA-exendin-3 and DOTA-octreotide) or at 45°C (DOTA-anti-CAIX antibody), the labelling efficiency was determined by instant thin layer chromatography. The effect of the ageing of the 111InCl3 stock on the labelling efficiency of DTPA-exendin-3 as well as the effect of increasing concentrations of Cd2+ (the decay product of 111In) were also examined. Specific activities obtained for DTPA-octreotide and DOTA-anti-CAIX antibody were five times higher in MES and HEPES buffer. Radiolabelling of DTPA-exendin-3, DOTA-exendin-3 and DTPA-anti-CAIX antibody in MES and HEPES buffer resulted in twofold higher specific activities than that in NaAc and NH4Ac. Labelling of DTPA-exendin-3 decreased with 66% and 73% for NaAc and NH4Ac, respectively, at day 11 after the production date of 111InCl3, while for MES and HEPES, the maximal decrease in the specific activity was 10% and 4% at day 11, respectively. The presence of 1 pM Cd2+ in the labelling mixture of DTPA-exendin-3 in NaAc and NH4Ac markedly reduced the labelling

  16. Simultaneous determination of DTPA, EDTA, and NTA by UV-visible spectrometry and HPLC.

    PubMed

    Laine, Pirita; Matilainen, Rose

    2005-08-01

    In this study, UV-visible spectrophotometry (UV-Vis) and high-performance liquid chromatography (HPLC) were used for simultaneous analysis of chelating agents diethylenetriamine pentaacetic acid (DTPA), ethylenediamine tetraacetic acid (EDTA), and nitrilotriacetic acid (NTA), as their metal chelates in dishwashing detergents, natural waters, and pulp mill water. The total amounts of the chelating agents in dishwashing detergents were verified by potentiometric titration with Fe(III) solution. Nickel(II) chelates were determined by UV-Vis and iron(III)chelates by HPLC and titration. Recoveries of DTPA, EDTA, and NTA from a standard mixture of analytes by UV-Vis were 107+/-7, 101+/-12 and 94+/-13%, respectively, and the recovery of the total amount of complexing agents was 99+/-4%. The limits of detection for DTPA, EDTA, and NTA were 667, 324, and 739 micromol L(-1), respectively. In HPLC measurements the optimized mobile phase contained 0.03 mol L(-1) sodium acetate, 0.002 mol L(-1) tetrabutylammonium bromide, and 5% methanol at pH 3.15 and the detection was by UV-Vis detection at 254 nm. All three complexing agents could be separated from each other in a simultaneous analysis in less than 5 min. The limits of detection were 0.34, 0.27, and 0.62 micromol L(-1) for DTPA, EDTA, and NTA, respectively. The total amounts of the analytes measured in the dishwashing detergents by the three techniques were found to be highly comparable (ANOVA: F=0.04, P=0.96). R(2) values were 0.99 for EDTA, 0.99 for NTA, and 0.99 for all the results when UV-Vis and HPLC determinations were compared using regression lines. The UV-Vis and HPLC methods were proved to be viable also for analyses of natural and pulp mill waters. The absence of matrix interferences was verified by the standard addition technique.

  17. Absorptive clearance of DTPA as an aerosol-based biomarker in the cystic fibrosis airway

    PubMed Central

    Corcoran, Timothy E; Thomas, Kristina M.; Myerburg, Michael M.; Muthukrishnan, Ashok; Weber, Lawrence; Frizzell, Raymond; Pilewski, Joseph M

    2010-01-01

    Biomarkers providing in vivo quantification of the basic elements of CF lung disease are needed. We questioned whether the absorption of a small, radiolabeled, hydrophilic molecule (Indium 111 DTPA) would be increased in CF airways. DTPA clearance has been used previously to assess epithelial permeability and may also be useful for quantifying liquid absorption. The absorptive clearance rate of DTPA was quantified in 10 CF and 11 control subjects using a novel aerosol technique. Subjects inhaled an aerosol containing non-absorbable Technetium-99m sulfur colloid (Tc-SC) particles and Indium-111 DTPA (In-DTPA). Tc-SC clearance from the lung is exclusively mucociliary while In-DTPA is cleared by both absorption and mucociliary clearance. The difference between the In-DTPA and Tc-SC clearance rates estimates In-DTPA absorption. Tc-SC (mucociliary) clearance was similar in central and peripheral zones in CF and non-CF. Total In-DTPA clearance was increased in both zones in CF. The absorptive component of In-DTPA clearance was increased in the airway-dominated central lung zones in CF (42 vs. 32 %/hr, p=0.03). The absorption of In-DTPA is increased in the CF airway. Further study is needed to understand the relative roles of fluid absorption, inflammation, and other mechanisms potentially affecting epithelial permeability and DTPA absorption. PMID:19717485

  18. Separation and characterization of the two diastereomers for [Gd(DTPA-bz-NH2)(H2O)]2-, a common synthon in macromolecular MRI contrast agents: their water exchange and isomerization kinetics.

    PubMed

    Burai, László; Tóth, Eva; Sour, Angélique; Merbach, André E

    2005-05-16

    Chiral, bifunctional poly(amino carboxylate) ligands are commonly used for the synthesis of macromolecular, Gd(III)-based MRI contrast agents, prepared in the objective of increasing relaxivity or delivering the paramagnetic Gd(III) to a specific site (targeting). Complex formation with such ligands results in two diastereomeric forms for the complex which can be separated by HPLC. We demonstrated that the diastereomer ratio for Ln(III) DTPA derivatives (approximately 60:40) remains constant throughout the lanthanide series, in contrast to Ln(III) EPTPA derivatives, where it varies as a function of the cation size with a maximum for the middle lanthanides (DTPA(5-) = diethylenetriaminepentaacetate; EPTPA(5-) = ethylenepropylenetriaminepentaacetate). The interconversion of the two diastereomers, studied by HPLC, is a proton-catalyzed process (k(obs) = k(1)[H(+)]). It is relatively fast for [Gd(EPTPA-bz-NH(2))(H(2)O)](2-) but slow enough for [Gd(DTPA-bz-NH(2))(H(2)O)](2-) to allow investigation of pure individual isomers (isomerization rate constants are k(1) = (3.03 +/- 0.07) x 10(4) and 11.6 +/- 0.5 s(-1) M(-1) for [Gd(EPTPA-bz-NH(2))(H(2)O)](2)(-) and [Gd(DTPA-bz-NH(2))(H(2)O)](2-), respectively). Individual water exchange rates have been determined for both diastereomers of [Gd(DTPA-bz-NH(2))(H(2)O)](2-) by a variable-temperature (17)O NMR study. Similarly to Ln(III) EPTPA derivatives, k(ex) values differ by a factor of 2 (k(ex)(298) = (5.7 +/- 0.2) x 10(6) and (3.1 +/- 0.1) x 10(6) s(-1)). This variance in the exchange rate has no consequence on the proton relaxivity of the two diastereomers, since it is solely limited by fast rotation. However, such difference in k(ex) will affect proton relaxivity when these diastereomers are linked to a slowly rotating macromolecule. Once the rotation is optimized, slow water exchange will limit relaxivity; thus, a factor of 2 in the exchange rate can lead to a remarkably different relaxivity for the diastereomer complexes

  19. Leaching and efficiency of six organic zinc fertilizers applied to navy bean crop grown in a weakly acidic soil of Spain.

    PubMed

    Gonzalez, D; Novillo, J; Rico, M I; Alvarez, J M

    2008-05-14

    Zinc contamination of groundwater from fertilizers applied to pulse crops is a potential problem, but the use of different types of organic chelates can minimize the contamination potential while still adequately feeding the crops. The objective of this study was to compare the leaching, distribution in fractions and availability, and relative effectiveness of Zn from six organic Zn fertilizers (zinc-ethylenediaminetetraacetate- N-2-hydroxyethylethylenediaminetriacetate (Zn-EDTA-HEDTA), Zn-HEDTA, zinc- S, S'-ethylenediaminedisuccinate (Zn- S, S-EDDS), zinc-polyhydroxyphenylcarboxylate, Zn-EDTA, and zinc-ethylenediaminedi(2-hydroxy-5-sulfophenylacetate) (Zn-EDDHSA)) applied to a navy bean ( Phaseolus vulgaris, L.) crop cultivated by applying different Zn levels, in a weakly acidic soil under greenhouse conditions. Zinc soil behavior was evaluated by diethylenetriaminepentaacetic acid-triethanolamine (DTPA-TEA), DTPA-ammonium bicarbonate (DTPA-AB), Mehlich-3, and BaCl 2 extractions and sequential fractionation. In all the fertilizer treatments, the percentage of labile Zn that remained in the soil was high with respect to the quantity of Zn applied, with values respectively ranging from 42 to 80% for Zn-EDDHSA and Zn-EDTA sources. A positive correlation with a high level of significance existed between the micronutrient concentration in the navy bean crop (total and soluble) and labile Zn fractions, available Zn, and easily leachable Zn ( r ranged from 0.89 to 0.95, P < 0.0001). The relatively high quantity of total Zn leached by applying Zn-EDTA and Zn-S,S-EDDS sources (11.9 and 6.0%, respectively, for the rate 10 mg of Zn kg(-1) of soil) poses a potential pollution risk for neighboring waters. It would seem recommendable to apply Zn-HEDTA or Zn-EDDHSA sources, even applied at the low rate (5 mg of Zn kg(-1) of soil), because they produced available Zn concentrations in the soil that were above the critical concentration and also produced high Zn concentrations in

  20. Synthesis of a novel antiestrogen radioligand (99mTc-TOR-DTPA).

    PubMed

    Yurt, Ayfer; Muftuler, Fazilet Zumrut B; Unak, Perihan; Yolcular, Seniha; Acar, Cigdem; Enginar, Huseyin

    2009-12-01

    This study was aimed at developing a hydrophilic radioligand as an antiestrogen drug derivative to be used for imaging breast tumors. Toremifene [TOR; 4-chloro-1,2-diphenyl-1-(4-(2-(N,N-di-methylamino)ethoxy)phenyl)-1-butene, as citrate salt] was selected as the starting material to be derived, since it has been used extensively as an antiestrogen drug for treatment and prevention of human breast cancer. An antiestrogen drug derivative, TOR attached to diethylenetriamine pentaacetic acid (DTPA), was synthesized by two experimental treatments, including a purification and a reaction step. We described the synthesis of this TOR derivative, (3Z)-4-{4-[2-(dimethylamino) ethoxy] phenyl}-3,4-diphenylbut-3-en-1-ylN,N-bis[2-(2,6-dioxomorpholin-4-yl)ethyl]glycinate (TOR-DTPA), in detail. Mass spectroscopy confirmed the expected structures. TOR-DTPA was labeled with technetium-99m ((99m)Tc), using stannous chloride (SnCl(2)) as the reducing agent. Biodistribution studies were performed on female Albino Wistar rats. Quality controls, radiochemical yield, and stability studies were done utilizing high-performance liquid chromatography, radioelectrophoresis, thin-layer chromatography, and thin-layer radiochromatography methods. The synthesized compound was found to be hydrophilic and anionic, with high stability for the duration of the testing period in vitro. The results indicated that the radiolabeled compound has estrogen-receptor specificity, especially for the breast tissue. It is highly possible that this compound could be used for imaging breast tumors as a novel technetium-labeled hydrophilic estrogen derivative radioligand.

  1. Evaluation of the efficiency of DTPA and other new chelating agents for removing neptunium from target organs.

    PubMed

    Paquet, F; Metivier, H; Poncy, J L; Burgada, R; Bailly, T

    1997-05-01

    Diethylenetriamine pentaacetic acid (DTPA) has been tested with 8 other new chelators for neptunium decorporation after systemic contamination in the rat. The ligands were injected intravenously at a dosage of 30 mumol kg-1 and the animals killed 24 h later. The results show that none of the chelators tested was efficient in removing significant amounts of the radionuclide from the body. In order to understand why these chelators were ineffective, in vitro approaches have since been developed in which high concentrations of DTPA were added to Np-bearing ligands in the blood, liver and skeleton. The main conclusions were that under our experimental conditions neptunium was not chelatable after its organ deposition.

  2. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

    SciTech Connect

    Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

    1982-11-01

    Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.

  3. Structural determination of Zn and Cd-DTPA complexes: MS, infrared, (13)C NMR and theoretical investigation.

    PubMed

    Silva, Vanézia L; Carvalho, Ruy; Freitas, Matheus P; Tormena, Cláudio F; Melo, Walclée C

    2007-12-31

    The joint application of MS, infrared and (13)C NMR techniques for the determination of metal-DTPA structures (metal=Zn and Cd; DTPA=diethylenetriaminepentacetic acid) is reported. Mass spectrometry allowed determining the 1:1 stoichiometry of the complexes, while infrared analysis suggested that both nitrogen and carboxyl groups are sites for complexation. The (13)C NMR spectrum for the cadmium-containing complex evidenced the existence of free and complexed carboxyl groups, due to a straight singlet at 179.0 ppm (free carboxylic (13)C) and to two broad singlets or a broad doublet at 178.3 ppm (complexed carboxylic (13)C, (2)J(Cd-C(=O))=45.2 Hz). A similar interpretation might be given for the zinc derivative and, with the aid of DFT calculations, structures for both complexes were then proposed.

  4. Synthesis, DTPA coupling and radio labeling of cationic aminodextran

    SciTech Connect

    Subramanian, G.; McAfee, J.G.; Schneider, R.F.; Zapf-Longo, C.; Palladino, E.; Lyons, B.J.; Roskopf, M.

    1984-01-01

    In glomerular diseases, the normal anionic charge of the basement membrane is lost at an early stage. Glomerular damage in rats has been detected more readily with cationic dextrans than with inulin. Hence, the authors attempted to demonstrate this phenomenon in vivo in rats with labeled cationic dextran. Aminated Dextran (AMDEX) was prepared by treating Dextran(mol. wt approx. = 15k) with sodium methoxide followed by a bromethylamine HBr in DMSO resulting in 10-25 aminogroups per mole. DTPA cyclic dianhydride was coupled to AMDEX using a weight ratio of 1:10 in 0.2 - 1.0 ml 0.42 M Hepes buffer at pH 7.4. Free DTPA was removed by gel filtration (Sephadex P6DG) or by using Centricon-10 (AMICON) centrifugal microconcentrators. AMDEX coupled with DTPA was labeled with Indium-111 in 0.25 M acetate buffer. Labeling yields were >90% by gel chromatography and electrophoresis (pH8.2 Barbitol buffer). AMEXDTPA was labeled also by ligand exchange with Tc-99m-Sn-citrate at neutral pH with a labeling yield of 30%. On electrophoresis, all the labeled samples retained their cationic character. The distribution of purified In-111 AMDEX, was compared with simultaneously IV injected Tc-99m DTPA in rats. The 2 hour urinary excretion, and renal clearance (calculated from the biexponential plasma clearance) were slower (70 to 80%) than those of DTPA, due to the larger molecular size of AMDEX. By 1 hr., 5% of the administered activity was retained in each kidney, probably due to adherence to anionic binding sites.

  5. Clearance of [sup 99m]Tc-DTPA and experimentally increased alveolar surfactant content

    SciTech Connect

    Bos, J.A.H.; Wollmer, P.; Bakker, W.; Hannappel, E.; Lachmann, B. Univ. of Lund Univ. of Erlangen )

    1992-04-01

    The authors measured clearance of [sup 99m]Tc-labeled diethylenetriamine pentaacetic acid ([sup 99m]Tc-DTPA) in rabbits with experimentally increased alveolar surfactant content. In one group of animals, surfactant production was increased by treatment with ambroxol, and another group of animals was treated with tracheal instillation of natural surfactant. A group of untreated control animals and animals treated with instillation of saline were also studied. Clearance was measured during standard conditions of mechanical ventilation and during ventilation with large tidal volumes. In ambroxol- and surfactant-treated groups, clearance rate was reduced compared with untreated control animals. In contrast, clearance rate increased after saline instillation. The differences were observed at both modes of ventilation. The findings indicate that the pulmonary surfactant system is a rate-limiting factor for the clearance of [sup 99m]Tc-DTPA and that the volume dependence of clearance is not explained by stretching of the alveolar wall only. 28 refs., 2 figs., 1 tab.

  6. On the use of speciation techniques and ab initio modelling to understand tetravalent actinide behavior in a biological medium: An(IV)DTPA case.

    PubMed

    Aupiais, J; Bonin, L; Den Auwer, C; Moisy, P; Siberchicot, B; Topin, S

    2016-03-07

    In the case of an accidental nuclear event, contamination of human bodies by actinide elements may occur. Such elements have the particularity to exhibit both radiological and chemical toxicities that may induce severe damages at several levels, depending on the biokinetics of the element. In order to eliminate the actinide elements before they are stored in target organs (liver, kidneys, or bone, depending on the element), sequestering agents must be quickly injected. However, to date, there is still no ideal sequestering agent, despite the recent interest in this topic due to contamination concerns. DTPA (diethylene triamine pentaacetic acid) is currently generating interest for the development of oral or alternative self-administrable forms. Although biokinetics data are mostly available, molecular scale characterization of actinide-DTPA complexes is still scarce. Nevertheless, strong interest is growing in the characterization of An(IV)DTPA(-) complexes at the molecular level because this opens the way for predicting the stability constants of unknown systems or even for developing new analytical strategies aimed at better and more selective decorporation. For this purpose, Extended X-ray Absorption Fine Structure (EXAFS) and Ab Initio Molecular Dynamics (AIMD) investigations were undertaken and compared with capillary electrophoresis (CE) used in a very unusual way. Indeed, it is commonly believed that CE is incapable of extracting structural information. In capillary electrophoresis, the electrophoretic mobility of an ion is a function of its charge and size. Despite very similar ratios, partial separations between An(IV)DTPA(-) species (An(IV) = Th, U, Np, Pu) were obtained. A linear relationship between the electrophoretic mobility and the actinide--oxygen distance calculated by AIMD was evidenced. As an example, the interpolated U-O distances in U(IV)DTPA(-) from CE-ICPMS experiments, EXAFS, AIMD, and the relationship between the stability constants and

  7. Preparation of (99m)Tc carbonyl DTPA-bevacizumab and its bioevaluation in a melanoma model.

    PubMed

    Kameswaran, Mythili; Pandey, Usha; Sarma, Haladhar Dev; Samuel, Grace

    2014-11-01

    The objective of this study was to explore the potential of (99m)Tc carbonyl labeled DTPA-bevacizumab as a tumor imaging agent. Bevacizumab (Avastin) is a humanized monoclonal antibody (MoAb) that inhibits the vascular endothelial growth factor (VEGF). Bevacizumab was conjugated with paraisothiocyanatobenzyl diethylenetriamine pentaacetic acid (p-SCN-Bn-DTPA) and subsequently radiolabeled with (99m)Tc via the (99m)Tc carbonyl synthon. The radioconjugate after purification was characterized by SE-HPLC and its in vitro stability was determined by histidine challenge experiments. Biodistribution studies to determine the uptake by tumors were carried out in melanoma model. The radiochemical purity of (99m)Tc carbonyl labeled antibody was >98 %. The radiolabeled antibody exhibited good stability in the histidine challenge experiments up to 24 h when stored at 37 °C. Biodistribution studies in mice bearing melanoma showed significant tumor uptake (6.9 ± 2.2 % ID/g at 24 h p.i.) which was reduced to 1.6 ± 0.4 % ID/g on co-injection with cold Bevacizumab. The (99m)Tc carbonyl-DTPA-bevacizumab conjugate with good radiochemical purity, excellent stability and good specificity for VEGF indicates its potential as a radioimmunoscintigraphy agent for various cancers.

  8. Detection of alveolar epithelial injury by 99mTC-DTPA radioaerosol inhalation lung scan following blunt chest trauma.

    PubMed

    Okudan, Berna; Han, Serdar; Baldemir, Makbule; Yildiz, Mustafa

    2004-10-01

    DTPA clearance rate is a reliable index of alveolar epithelial permeability, and is a highly sensitive marker of pulmonary epithelial damage, even of mild degree. In this study, 99mTc-DTPA aerosol inhalation scintigraphy was used to assesss the pulmonary epithelial membrane permeability and to investigate the possible application of this permeability value as an indicator of early alveolar or interstitial changes in patients with blunt chest trauma. A total of 26 patients was chest trauma (4 female, 22 male, 31-80 yrs, mean age; 53+/-13 yrs) who were referred to the emergency department in our hospital participated in this tsudy. Technetium-99m diethylene triamine pentaacetic acid (DTPA) aerosol inhalation scintigraphy was performed on the first and thirtieth days after trauma. Clearance half times (T1/2) were calculated by placing a mono-exponential fit on the curves. Penetration index (PI) was calculated on the first-minute image. On the first day, mean T1/2 value of the whole lung was 63+/-19 minutes (min), and thirtieth day mean T1/2 value was 67+/-21 min. On the first day, mean PI values of the lung and 30th day mean PI value were 0.60+/-0.05, and 0.63+/-0.05, respectively. Significant changes were observed in radioaerosol clearance and penetration indices. Following chest trauma, clearance of 99mTc-DTPA increased owing to breakdown of the alveolar-capillary barrier. This increase in the epithelial permeability of the lung appears to be an early manifestation of lung disease that may lead to efficient therapy in the early phase.

  9. Effect of DTPA on Cd solubility in soil--accumulation and subsequent toxicity to lettuce.

    PubMed

    Mehmood, Faisal; Rashid, Audil; Mahmood, Tariq; Dawson, Lorna

    2013-02-01

    In a controlled environment experiment, using Cd spiked soil, lettuce plants were grown under a range of DTPA levels and were subsequently harvested to determine levels of phytoaccumulation. Cadmium phytoaccumulation significantly increased with increasing soil Cd level (P<0.05) but unexpectedly decreased with increasing DTPA levels, despite the fact that solubility of Cd was increased in the soil. Cadmium translocation (from root to shoot) increased after DTPA application. Lettuce growth was inhibited by both Cd and DTPA (at and above 10 and 500 mg kg(-1) respectively), as a result of higher Cd mobility and subsequent toxicity which was caused by DTPA higher dosages. Metal solubility in the soil (ranged between 2.8 and 26.5 mg kg(-1)) was found to be significantly higher (P<0.01) as compared to control with increasing DTPA levels even after 3 months of DTPA application. Cadmium tissue concentration in all DTPA treatments was less than in the corresponding control treatment, indicating a negative effect of DTPA application on Cd uptake. In conclusion, lettuce was an unsuitable plant species for Cd accumulation, at least when associated with a DTPA chelator. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Gd-DTPA Adsorption on Chitosan/Magnetite Nanocomposites

    NASA Astrophysics Data System (ADS)

    Pylypchuk, Ie. V.; Kołodyńska, D.; Kozioł, M.; Gorbyk, P. P.

    2016-03-01

    The synthesis of the chitosan/magnetite nanocomposites is presented. Composites were prepared by co-precipitation of iron(II) and iron(III) salts by aqueous ammonia in the 0.1 % chitosan solution. It was shown that magnetite synthesis in the chitosan medium does not affect the magnetite crystal structure. The thermal analysis data showed 4.6 % of mass concentration of chitosan in the hybrid chitosan/magnetite composite. In the concentration range of initial Gd-DTPA solution up to 0.4 mmol/L, addition of chitosan to magnetite increases the adsorption capacity and affinity to Gd-DTPA complex. The Langmuir and Freundlich adsorption models were applied to describe adsorption processes. Nanocomposites were characterized by scanning electron microscopy (SEM), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and specific surface area determination (ASAP) methods.

  11. Analysis of Pharmacokinetics of Gd-DTPA for Dynamic Contrast-enhanced Magnetic Resonance Imaging

    PubMed Central

    Taheri, Saeid; Jon Shah, N.; Rosenberg, Gary A.

    2016-01-01

    The pharmacokinetics (PK) of the contrast agent Gd-DTPA administered intravenously (i.v.) for contrast-enhanced MR imaging (DCE-MRI) is an important factor for quantitative data acquisition. We studied the effect of various initial bolus doses on the PK of Gd-DTPA and analyzed population PK of a lower dose for intra-subject variations in DCE-MRI. First, fifteen subjects (23–85 years, M/F) were randomly divided into four groups for DCE-MRI with different Gd-DTPA dose: group-I, 0.1mmol/kg, n=4; group-II, 0.05 mmol/kg, n=4; group-III, 0.025mmol/kg, n=4; and group-IV, 0.0125 mmol/kg, n=3. Sequential fast T1 mapping sequence, after a bolus i.v. Gd-DTPA administered, and a linear T1-[Gd-DTPA] relationship were used to estimate the PK of Gd-DTPA. Secondly, MR-acquired PK of Gd-DTPA from 58 subjects (28–80 years, M/F) were collected retrospectively, from an ongoing study of the brain using DCE-MRI with Gd-DTPA at 0.025 mmol/kg, to statistically analyze population PK of Gd-DTPA. We found that the PK of Gd-DTPA (i.v. 0.025 mmol/kg) had a half-life of 37.3 ± 6.6 mins, and was a better fit into a linear T1-[Gd-DTPA] relationship than higher doses (up to 0.1 mmol/kg). The area under the curve (AUC) for 0.025 mmol/kg was 3.37± 0.46, which was a quarter of AUC of 0.1 mmol/kg. In population analysis, a dose of 0.025 mmol/kg of Gd-DTPA provided less than 5% subject-dependent variation in the PK of Gd-DTPA. Administration of 0.025 mmol/kg Gd-DTPA enable us to estimate [Gd-DTPA] from T1 by using a linear relationship that has a lower estimation error compared to a non-linear relationship. DCE-MRI with a quarter dose of Gd-DTPA is more sensitive to detect changes in [Gd-DTPA]. PMID:27109487

  12. Preclinical characterisation of 111In-DTPA-trastuzumab

    PubMed Central

    Lub-de Hooge, Marjolijn N; Kosterink, Jos G W; Perik, Patrick J; Nijnuis, Hugo; Tran, Ly; Bart, Joost; Suurmeijer, Albert J H; de Jong, Steven; Jager, Pieter L; de Vries, Elisabeth G E

    2004-01-01

    Trastuzumab (Herceptin®) is a recombinant humanised IgG1 monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), used for metastatic breast cancer treatment. Radiolabelled trastuzumab may have several future applications for diagnostic use. The aim of the present study was to develop clinical grade 111Indium (111In) radiolabelled trastuzumab, to evaluate the stability and immunoreactivity of the tracer and to perform a biodistribution study in human tumour-bearing mice. Trastuzumab was radiolabelled with 111In using DTPA as a chelator. 111In-DTPA-trastuzumab (labelling yield 92.3±2.3%, radiochemical purity 97.0±1.5%) is stable in PBS when stored at 4°C for more than 14 days. The immunoreactive fraction determined by cell-binding assays, using the HER2-overexpressing human ovarian SK-OV-3 tumour cell line, was 0.87±0.06. Biodistribution and tumour targeting were studied in HER2 receptor-positive and -negative tumour-bearing athymic mice. The HER2-positive tumour showed (9.77±1.14% injected dose per gram (ID g−1)) substantial uptake of the labelled antibody already after 5 h. The difference in uptake between HER2-positive versus -negative tumours was even more pronounced 3 days after injection (16.30±0.64% ID g−1), and was visualised by radioimmunoscintigraphy. Liver, spleen and kidney showed marked tracer uptake. In summary, trastuzumab can be efficiently radiolabelled with 111In with high labelling yields and high stability. 111In-DTPA-trastuzumab selectively binds to the human HER2 receptor both in vitro and in vivo in animals. Therefore, 111In-DTPA-trastuzumab appears suitable for clinical use. PMID:15289297

  13. Clearance of Tc-99m DTPA in hemodialysis and peritoneal dialysis: concise communication

    SciTech Connect

    Wainer, E.; Boner, G.; Lubin, E.; Rosenfeld, J.B.

    1981-09-01

    The clearance of Tc-99m DTPA was studied in 14 patients undergoing hemodialysis (HD) or peritoneal dialysis (PD). Mean Tc-99m DTPA clearance during HD was 37.8% +/- 10.1 of creatinine clearance. Mean Tc-99m DTPA clearance in PD was 65.1% +/- 10.3 of creatinine clearance. Tc-99m DTPA, with a larger molecular weight than that of creatinine, is cleared relatively better during PD than during HD. Thus Tc-99m DTPA may be used in the assessment of the effectiveness of different dialytic treatments for substances of similar molecular weight. In addition, our study shows that clearance of DTPA both in HD and PD is sufficiently high to allow the removal of this chelating agent in patients with renal failure.

  14. Tc-99m DTPA uptake in extramedullary plasmacytoma of the retroperitoneum

    SciTech Connect

    Aburano, T.; Yokoyama, K.; Michigishi, T.; Tonami, N.; Hisada, K.

    1988-12-01

    A case is presented in which uptake of Tc-99m DTPA has been demonstrated in an extramedullary plasmacytoma of the retroperitoneum. Because Ga-67 citrate does not concentrate in the same areas as Tc-99m DTPA, a radionuclide-specific uptake mechanism may be present. Extramedullary plasmacytoma should be included in the list of possible causes if extrarenal or extracentral nervous system uptake of Tc-99m DTPA occurs.

  15. Health economic evaluation of Gd-EOB-DTPA MRI vs ECCM-MRI and multi-detector computed tomography in patients with suspected hepatocellular carcinoma in Thailand and South Korea.

    PubMed

    Lee, Jeong-Min; Kim, Myeong-Jin; Phongkitkarun, Sith; Sobhonslidsuk, Abhasnee; Holtorf, Anke-Peggy; Rinde, Harald; Bergmann, Karsten

    2016-08-01

    The effectiveness of treatment decisions and economic outcomes of using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) were compared with extracellular contrast media-enhanced MRI (ECCM-MRI) and multi-detector computed tomography (MDCT) as initial procedures in patients with suspected hepatocellular carcinoma (HCC) in South Korea and Thailand. A decision-tree model simulated the clinical pathway for patients with suspected HCC from the first imaging procedure to a confirmed treatment decision. Input data (probabilities and resource consumptions) were estimated and validated by clinical experts. Costs for diagnostic alternatives and related treatment options were derived from published sources, taking into account both payer's and hospital's perspectives. All experts from Korea and Thailand agreed that Gd-EOB-DTPA-MRI yields the highest diagnostic certainty and minimizes the need for additional confirmatory diagnostic procedures in HCC. In Korea, from the payer's perspective, total cost was USD $3087/patient to reach a confirmed treatment decision using Gd-EOB-DTPA-MRI (vs $3205/patient for MDCT and $3403/patient for ECCM-MRI). From the hospital's perspective, Gd-EOB-DTPA-MRI incurred the lowest cost ($2289/patient vs $2320/patient and $2528/patient, respectively). In Thailand, Gd-EOB-DTPA-MRI was the least costly alternative for the payer ($702/patient vs $931/patient for MDCT and $873/patient for ECCM-MRI). From the hospital's perspective, costs were $1106/patient, $1178/patient, and $1087/patient for Gd-EOB-DTPA-MRI, MDCT, and ECCM-MRI, respectively. Gd-EOB-DTPA-MRI as an initial imaging procedure in patients with suspected HCC provides better diagnostic certainty and relevant statutory health insurance cost savings in Thailand and Korea, compared with ECCM-MRI and MDCT.

  16. Immune activity and biodistribution of polypeptide K237 and folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles radiolabeled with 99mTc

    PubMed Central

    Wu, Yufeng; Huang, Xuanzhang; Chen, Jie; Xia, Junyong; Jiang, Hao; Ma, Jing; Wu, Jian

    2016-01-01

    In a previous study, amphiphilic copolymer, polypeptide K237 (HTMYYHHYQHHL) and folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (K237/FA-PEG-PLGA) nanoparticles were developed and studied as a drug carrier. To further promote the clinical application of K237/FA-PEG-PLGA nanoparticles and provide guidance for future research, we need to examine their specific biodistribution in vivo. In this study, K237/FA-PEG-PLGA nanoparticles were effectively labeled by a direct method with Technetium-99m (99mTc) using stannous chloride as a reducing agent. The optimal stability of the labeled nanoparticles was determined by evaluating their radiochemical purity in serum, physiological saline, diethylenetriaminepentaacetic acid (DTPA) and cysteine solutions. The affinity of ligands and receptors was elicited by cell binding and blocking experiments in KDR/folate receptor high expressing SKOV-3 ovarian cancer cells. The nanoparticles biodistribution was studied after intravenous administration in healthy mice xenografted with SKOV-3 cells. A higher percent injected dose per gram of tissue (% ID/g) was observed in liver, kidney, spleen, blood and tumor at 3 and 9 h post-injection. Scintigraphic images revealed that the radioactivity was mainly concentrated in tumor, liver, kidney and bladder; and in the heart, lung, and muscle was significantly lower at 3 h. The radioactivity distribution in the images is consistent with the in vivo biodistribution data. Our works demonstrated that K237/FA-PEG-PLGA nanoparticles have great potential as biodegradable drug carriers, especially for tumors expressing the folate and KDr receptor. PMID:27791199

  17. Synthesis and application of a novel cysteine-based DTPA-NCS for targeted radioimmunotherapy.

    PubMed

    Lee, So-Young; Hong, Young Don; Kim, Hak-Sung; Choi, Sun-Ju

    2013-04-01

    For the development of safe and effective protein-based radiolabeled complexes such as radioimmunotherapy (RIT), the selection of the radionuclides and the chelating agents used for the radiolabeling of tumor-targeting molecules is a critical factor. We aim to synthesize a novel bifunctional chelating agent containing the isothiocyanate group for easy conjugation with antibodies having the characteristics of high stable chelation with therapeutic radionuclides. We have synthesized the DTPA analogue retaining L-cysteine as a core ligand of the thiol group. The chelating power of cysteine-based DTPA-NCS (cys-DTPA-NCS) was compared with that of commercial ρ-SCN-Bn-DTPA. In an application, the cetuximab was radioimmunoconjugated with (177)Lu using cys-DTPA-NCS. The affinity was tested in a cell line overexpressing EGFR. A therapy study was conducted in nude mice with subcutaneous HT-29 xenografts. The cys-DTPA-NCS presents an excellent ability to chelate as compared to the ρ-SCN-Bn-DTPA. For mean ratio chemical labeling yields of 95%, the result was 0.97. (177)Lu-cys-DTPA-NCS-cetuximab was prepared under ambient condition with a high radiolabeling yield and the radiochemical purity was sustained for at least 6days. The IC50 value of the (177)Lu-labeled cetuximab was 10nM (95% confidence). The stability and therapeutic efficacy of the candidate radiopharmaceutical were verified. The new DTPA derivative, cys-DTPA-NCS, is a good bifunctional chelating agent that can be used for protein-based radiopharmaceutical using lanthanides such as (177)Lu and (90)Y. The prepared (177)Lu-cys-DTPA-NCS-cetuximab can be used for the diagnosis and treatment of human colorectal tumor. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Ustur whole body case 0269: demonstrating effectiveness of i.v. CA-DTPA for Pu.

    PubMed

    James, A C; Sasser, L B; Stuit, D B; Glover, S E; Carbaugh, E H

    2007-01-01

    This whole body donation case (USTUR Registrant) involved a single acute inhalation of an acidic Pu(NO3)4 solution in the form of an aerosol 'mist'. Chelation treatment with intravenously (i.v.) Ca-EDTA was initiated on the day of the intake, and continued intermittently over 6 months. After 2.5 y with no further treatment, a course of i.v. Ca-DTPA was administered. A total of 400 measurements of 239+240Pu excreted in urine were recorded; starting on the first day (both before and during the initial Ca-EDTA chelation) and continuing for 37 y. This sampling included all intervals of chelation. In addition, 91 measurements of 239+240Pu-in-feces were recorded over this whole period. The Registrant died about 38 y after the intake, at age 79 y, with extensive carcinomatosis secondary to adenocarcinoma of the prostate gland. At autopsy, all major soft tissue organs were harvested for radiochemical analyses of their 238Pu, 239+240Pu and 241Am content. Also, all types of bone (comprising about half the skeleton) were harvested for radiochemical analyses, as well as samples of skin, subcutaneous fat and muscle. This comprehensive data set has been applied to derive 'chelation-enhanced' transfer rates in the ICRP Publication 67 plutonium biokinetic model, representing the behaviour of blood-borne and tissue-incorporated plutonium during intervals of therapy. The resulting model of the separate effects of i.v. Ca-EDTA and Ca-DTPA chelation shows that the therapy administered in this case succeeded in reducing substantially the long-term burden of plutonium in all body organs, except for the lungs. The calculated reductions in organ content at the time of death are approximately 40% for the liver, 60% for other soft tissues (muscle, skin, glands, etc.), 50% for the kidneys and 50% for the skeleton. Essentially, all of the substantial reduction in skeletal burden occurred in trabecular bone. This modelling exercise demonstrated that 3-y-delayed Ca-DTPA therapy was as effective

  19. USTUR WHOLE BODY CASE 0269: DEMONSTRATING EFFECTIVENESS OF I.V. CA-DTPA FOR PU

    SciTech Connect

    James, Anthony C.; Sasser , Lyle B.; Stuit, Dorothy B.; Glover, Samuel E.; Carbaugh, Eugene H.

    2008-01-28

    This whole body donation case (USTUR Registrant) involved a single acute inhalation of an acidic Pu(NO3)4 solution in the form of an aerosol ‘mist.’ Chelation treatment with i.v. Ca-EDTA was initiated on the day of the intake, and continued intermittently over 6 months. After 2½ years with no further treatment, a course of i.v. Ca-DTPA was administered. A total of 400 measurements of 239+240Pu excreted in urine were recorded; starting on the first day (both before and during the initial Ca-EDTA chelation), and continuing for 37 years. This sampling included all intervals of chelation. In addition, 91 measurements of 239+240Pu-in-feces were recorded over this whole period. The Registrant died about 38 years after the intake, at age 79 y, with extensive carcinomatosis secondary to adenocarcinoma of the prostate gland. At autopsy, all major soft tissue organs were harvested for radiochemical analyses of their 238Pu, 239+240Pu and 241Am content. Also, all types of bone (comprising about half the skeleton) were harvested for radiochemical analyses, as well as samples of skin, subcutaneous fat and muscle. This comprehensive dataset has been applied to derive ‘chelation-enhanced’ transfer rates in the ICRP Publication 67 plutonium biokinetic model, representing the behaviour of blood-borne and tissue-incorporated plutonium during intervals of therapy. The resulting model of the separate effects of i.v. Ca-EDTA and Ca-DTPA chelation shows that the therapy administered in this case succeeded in reducing substantially the long-term burden of plutonium in all body organs, except for the lungs. The calculated reductions in organ content at the time of death are approximately 40% for the liver, 60% for other soft tissues (muscle, skin, glands, etc.), 50% for the kidneys, and 50% for the skeleton. Essentially all of the substantial reduction in skeletal burden occurred in trabecular bone. This modeling exercise demonstrated that 3-y-delayed Ca-DTPA therapy was as

  20. Pulmonary 99mTc-DTPA aerosol clearance and survival in usual interstitial pneumonia (UIP)

    PubMed Central

    Mogulkoc, N; Brutsche, M; Bishop, P; Murby, B; Greaves, M; Horrocks, A; Wilson, M; McCullough, C; Prescott, M; Egan, J

    2001-01-01

    BACKGROUND—Clearance of inhaled technetium 99m-labelled diethylenetriamine penta-acetic acid (99mTc-DTPA) from the lungs is a potential indicator of disease progression in patients with idiopathic pulmonary fibrosis (IPF).
METHODS—We prospectively analysed the usefulness of this technique for predicting survival in 106 non-smoking patients with usual interstitial pneumonia (UIP) pattern IPF diagnosed by high resolution CT (HRCT) scanning or histological examination (M/F 65/41, mean (SD) age 61 (11) years). DTPA clearance was analysed according to both mono-exponential and bi-exponential models. Half times for the fast (t0.5F) and slow (t0.5S) components of clearance, the percentage contribution of the fast component (fF), and half time for mono-exponential approximation to the early part of the clearance curve (t0.5) were calculated.
RESULTS—The patients had substantially faster t0.5 (mean 23.9 (9.6) minutes) than normal values (>45 minutes). Thirty seven patients (35%) died during follow up (median 15 months). Univariate Cox regression analysis identified significant predictors of survival as age, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), total lung capacity (TLC), % predicted TLC, carbon monoxide transfer factor (TLCO), % predicted TLCO, arterial oxygen tension (PaO2), oxygen saturation, t0.5F, and HRCT fibrosis score. Multiple stepwise Cox regression analysis identified t0.5F (p=0.03, hazard ratio 0.747, 95% CI 0.578 to 0.964), % predicted TLC (p=0.02, hazard ratio 0.976, 95% CI 0.956 to 0.995), % predicted TLCO (p=0.003, hazard ratio 0.960, 95% CI 0.935 to 0.986), and age (p=0.003, hazard ratio 1.062, 95% CI 1.021 to 1.104) as independent predictors of survival.
CONCLUSION—These data suggest that 99mTc-DTPA clearance t0.5F measurement may predict survival in patients with UIP pattern IPF.

 PMID:11713353

  1. An Evaluation of the Chelating Agent EDDS for Floriculture Crop Production

    USDA-ARS?s Scientific Manuscript database

    Aminopolycarboxylic acid (APCA) ligands (chelating agents) like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are commonly used in soluble fertilizers to supply copper (Cu), iron (Fe), manganese (Mn), and/or zinc (Zn) to plants. When complexed with Fe, EDTA and...

  2. Iron-[S,S']-EDDS (FeEDDS) Chelate as an Iron Source for Horticultural Crop Production: Marigold Growth and Nutrition, Spectral Properties, and Photodegradation

    USDA-ARS?s Scientific Manuscript database

    Aminopolycarboxylic acid (APCA) complexones, commonly referred to as ligands or chelating agents, like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are commonly used in soluble fertilizers to supply copper (Cu), iron (Fe), manganese (Mn), and/or zinc (Zn) to p...

  3. Incidental 99mTc-DTPA Uptake in Tarlov Cysts on Radionuclide SPECT/CT Cisternography.

    PubMed

    Vamadevan, Shankar; Le, Ken; Bui, Chuong; Mansberg, Robert

    2017-04-01

    Sacral perineural cysts are also known as Tarlov cysts. A 58-year-old man with suspected intracranial hypotension was evaluated with Tc-DTPA radionuclide cisternography. Radionuclide planar and SPECT/CT cisternography revealed Tc-DTPA uptake in sacral lesions. Spine MRI confirmed Tarlov cysts at the S1 and S2 levels.

  4. Spontaneous perforation of the ureter diagnosed on technetium 99m DTPA excretory urography

    SciTech Connect

    Barasch, E.; Kashdan, B.; Rathore, A.

    1988-01-01

    A case of nontraumatic rupture of the ureter secondary to a nonopaque calculus is presented. Because of the inherent high image contrast caused by the leak of technetium 99m-DTPA-labeled urine, the technetium 99m-DTPA excretory urogram is seen as an alternative to the intravenous urogram or contrast-enhanced computed tomography in selected cases of suspected ureteral rupture.

  5. Comparison of Gd-Bz-TTDA, Gd-EOB-DTPA, and Gd-BOPTA for dynamic MR imaging of the liver in rat models.

    PubMed

    Jaw, Twei-Shiun; Chen, Shih-Hsien; Wang, Yun-Ming; Hsu, Jui-Sheng; Kuo, Yu-Ting; Chiu, Yen-Yu; Tsai, Kun-Bow; Hsieh, Tsyh-Jyi; Liu, Gin-Chung

    2012-03-01

    To evaluate the competitive potential of a new lipophilic paramagnetic complex, Gd-Bz-TTDA [4-benzyl-3,6,10-tri (carboxymethyl)-3,6,10-triazado-decanedioic acid] compared with two other commercially available MR hepatobiliary contrast agents, gadobenate dimeglumine (Gd-BOPTA) and gadoxetic acid (Gd-EOB-DTPA), dynamic MR imaging studies were performed on normal and hepatocellular carcinoma (HCC) rat models using a 1.5-Tesla MR scanner. The results indicate that normal rats that were injected with 0.1 mmol/kg Gd-Bz-TTDA showed significantly more intense and persistent liver enhancement than those that were injected with the same dose of Gd-EOB-DTPA or Gd-BOPTA. All of these agents showed similar enhancement patterns in the implanted HCC. The liver-lesion contrast-to-noise ratios were higher and more persistent in rats that were injected with Gd-Bz-TTDA. These results indicate that Gd-Bz-TTDA is comparable with the commercially available hepatobiliary agents, Gd-EOB-DTPA and Gd-BOPTA, and can result in more intense and prolonged liver enhancement while still providing better liver-lesion discrimination. These results warrant further large-scale studies.

  6. Radiolabeled γ-polyglutamic acid complex as a nano-platform for sentinel lymph node imaging.

    PubMed

    Sano, Kohei; Iwamiya, Yuriko; Kurosaki, Tomoaki; Ogawa, Mikako; Magata, Yasuhiro; Sasaki, Hitoshi; Ohshima, Takashi; Maeda, Minoru; Mukai, Takahiro

    2014-11-28

    We established a ternary anionic complex constructed with polyamidoamine dendrimer (4th generation; G4) modified with chelating agents (diethylenetriamine pentaacetic acid (DTPA) derivative), polyethyleneimine (PEI), and γ-polyglutamic acid (PGA) as a safe nano-platform for molecular imaging. We prepared indium-111-labeled DTPA-G4/PEI/γ-PGA, and evaluated the effectiveness as a nuclear imaging probe for sentinel lymph node (LN), the first LN that drains the primary tumor. (111)In-DTPA-G4/PEI with strong cationic charge agglutinated with erythrocytes and showed extremely high cytotoxicity. By contrast, the anionic (111)In-DTPA-G4/PEI/γ-PGA had little agglutination activity with erythrocytes and no cytotoxicity, indicating their high biocompatibility. (111)In-DTPA-G4/PEI/γ-PGA was highly taken up by macrophage cells (high populations in LNs) comparable to (111)In-DTPA-G4/PEI. The uptake mechanisms of (111)In-DTPA-G4/PEI/γ-PGA were suggested to be both phagocytosis and γ-PGA-specific pathway. Upon administration of each (111)In-labeled nano-platform into rat footpads intradermally, significantly higher radioactivity of (111)In-DTPA-G4/PEI/γ-PGA was observed in the first draining popliteal LN when compared with that of (111)In-DTPA-G4/PEI. Moreover, (111)In-DTPA-G4/PEI/γ-PGA clearly visualized the sentinel LN with single photon emission computed tomography (SPECT) compared with (111)In-DTPA-G4/PEI. Thus, (111)In-DTPA-G4/PEI/γ-PGA can be useful as a nano-platform for molecular imaging including sentinel LN imaging. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Structure of a single model to describe plutonium and americium decorporation by DTPA treatments.

    PubMed

    Fritsch, P; Sérandour, A L; Grémy, O; Phan, G; Tsapis, N; Fattal, E; Benech, H; Deverre, J R; Poncy, J L

    2010-10-01

    The aim of this study is to propose a single modeling structure to describe both plutonium and americium decorporation by DTPA, which is based on hypotheses mostly validated by experimental data. Decorporation efficacy of extracellular retention depends on the concentration ratio of DTPA vs. actinides and varies in each compartment according to the amount of biological ligands and their affinity for actinides. By contrast, because the relatively long residence time of DTPA after its cell internalization and the stability of actinide-DTPA complexes, intracellular decorporation efficacy is mainly controlled by a DTPA/actinide ratio, which is specific to each retention compartment. Although the affinity of DTPA is much lower for americium than for plutonium, a larger decorporation of americium can be obtained, which is explained by different biological ligands and/or their affinity for the actinide. Altogether, these results show that the relative contribution of intra vs. extracellular decorporation varies depending on the actinide, the chemical form of radionuclides, the galenic formulation of DTPA, and the treatment schedule.

  8. LAT-1 based primary breast cancer detection by [99m]Tc-labeled DTPA-bis-methionine scintimammography: first results using indigenously developed single vial kit preparation.

    PubMed

    Sharma, Sarika; Singh, Baljinder; Mishra, Anil K; Rathod, Deepti; Hazari, Puja Panwar; Chuttani, Krishna; Chopra, Shalini; Singh, Paramvir Mangat; Abrar, M L; Mittal, Bhagwant R; Singh, Gurpreet

    2014-09-01

    To evaluate the diagnostic utility of a single vial ready to label with [99m]Tc kit preparation of DTPA-bis-methionine (DTPA-bis-MET) for the detection of primary breast cancer. The conjugate (DTPA-bis-MET) was synthesized by covalently conjugating two molecules of methionine to DTPA and formulated as a single vial ready to label with [99m]Tc lyophilized kit preparations. Thirty female patients (mean age=47.5±11.8 years; range=21-69 years) with radiological/clinical evidence of having primary breast carcinoma were subjected to [99m]Tc-methionine scintigraphy. The whole body (anterior and posterior) imaging was performed on all the patients at 5 minutes, 10 minutes, 1 hour, 2 hours, and 4 hours following an intravenous administration of 555-740 MBq radioactivity of [99m]Tc-methionine. In addition, scintimammography (static images; 256×256 matrix) at 1, 2, and 4 hours was also performed on all the patients. The resultant radiolabel, that is, [99m]Tc-DTPA-bis-MET, yielded high radiolabeling efficiency (>97.0%), radiochemical purity (166-296 MBq/μmol), and shelf life (>3 months). The radiotracer primarily gets excreted through the kidneys and localizes in the breast cancer lesions with high target-to-nontarget ratios. The mean±SD ratios on the scan-positive lesions acquired at 1, 2, and 4 hours postinjection were 3.6±0.48, 3.10±0.24, and 2.5±0.4, respectively. [99m]Tc-methionine scintimammography demonstrated an excellent sensitivity and positive predictive value of 96.0% each for the detection of primary breast cancer. Ready to label single vial kit formulations of DTPA-bis-MET can be easily synthesized as in-house production and conveniently used for the scintigraphic detection of breast cancer and other methionine-dependent tumors expressing the L-type amino acid transporter-1 receptor. The imaging technique thus could be a potential substitute for the conventional single-photon emission computed tomography (SPECT)-based tumor imaging agents, especially

  9. LAT-1 Based Primary Breast Cancer Detection by [99m]Tc-Labeled DTPA-Bis-Methionine Scintimammography: First Results Using Indigenously Developed Single Vial Kit Preparation

    PubMed Central

    Sharma, Sarika; Mishra, Anil K.; Rathod, Deepti; Hazari, Puja Panwar; Chuttani, Krishna; Chopra, Shalini; Singh, Paramvir Mangat; Abrar, M.L.; Mittal, Bhagwant R.; Singh, Gurpreet

    2014-01-01

    Abstract Objective: To evaluate the diagnostic utility of a single vial ready to label with [99m]Tc kit preparation of DTPA-bis-methionine (DTPA-bis-MET) for the detection of primary breast cancer. Methods: The conjugate (DTPA-bis-MET) was synthesized by covalently conjugating two molecules of methionine to DTPA and formulated as a single vial ready to label with [99m]Tc lyophilized kit preparations. Thirty female patients (mean age=47.5±11.8 years; range=21–69 years) with radiological/clinical evidence of having primary breast carcinoma were subjected to [99m]Tc-methionine scintigraphy. The whole body (anterior and posterior) imaging was performed on all the patients at 5 minutes, 10 minutes, 1 hour, 2 hours, and 4 hours following an intravenous administration of 555–740 MBq radioactivity of [99m]Tc-methionine. In addition, scintimammography (static images; 256×256 matrix) at 1, 2, and 4 hours was also performed on all the patients. Results: The resultant radiolabel, that is, [99m]Tc-DTPA-bis-MET, yielded high radiolabeling efficiency (>97.0%), radiochemical purity (166–296 MBq/μmol), and shelf life (>3 months). The radiotracer primarily gets excreted through the kidneys and localizes in the breast cancer lesions with high target-to-nontarget ratios. The mean±SD ratios on the scan-positive lesions acquired at 1, 2, and 4 hours postinjection were 3.6±0.48, 3.10±0.24, and 2.5±0.4, respectively. [99m]Tc-methionine scintimammography demonstrated an excellent sensitivity and positive predictive value of 96.0% each for the detection of primary breast cancer. Conclusion: Ready to label single vial kit formulations of DTPA-bis-MET can be easily synthesized as in-house production and conveniently used for the scintigraphic detection of breast cancer and other methionine-dependent tumors expressing the L-type amino acid transporter-1 receptor. The imaging technique thus could be a potential substitute for the conventional single-photon emission computed

  10. The Necrosis-Avid Small Molecule HQ4-DTPA as a Multimodal Imaging Agent for Monitoring Radiation Therapy-Induced Tumor Cell Death.

    PubMed

    Stammes, Marieke A; Maeda, Azusa; Bu, Jiachuan; Scollard, Deborah A; Kulbatski, Iris; Medeiros, Philip J; Sinisi, Riccardo; Dubikovskaya, Elena A; Snoeks, Thomas J A; van Beek, Ermond R; Chan, Alan B; Löwik, Clemens W G M; DaCosta, Ralph S

    2016-01-01

    Most effective antitumor therapies induce tumor cell death. Non-invasive, rapid and accurate quantitative imaging of cell death is essential for monitoring early response to antitumor therapies. To facilitate this, we previously developed a biocompatible necrosis-avid near-infrared fluorescence (NIRF) imaging probe, HQ4, which was radiolabeled with (111)Indium-chloride ((111)In-Cl3) via the chelate diethylene triamine pentaacetic acid (DTPA), to enable clinical translation. The aim of the present study was to evaluate the application of HQ4-DTPA for monitoring tumor cell death induced by radiation therapy. Apart from its NIRF and radioactive properties, HQ4-DTPA was also tested as a photoacoustic imaging probe to evaluate its performance as a multimodal contrast agent for superficial and deep tissue imaging. Radiation-induced tumor cell death was examined in a xenograft mouse model of human breast cancer (MCF-7). Tumors were irradiated with three fractions of 9 Gy each. HQ4-DTPA was injected intravenously after the last irradiation, NIRF and photoacoustic imaging of the tumors were performed at 12, 20, and 40 h after injection. Changes in probe accumulation in the tumors were measured in vivo, and ex vivo histological analysis of excised tumors was performed at experimental endpoints. In addition, biodistribution of radiolabeled [(111)In]DTPA-HQ4 was assessed using hybrid single-photon emission computed tomography-computed tomography (SPECT-CT) at the same time points. In vivo NIRF imaging demonstrated a significant difference in probe accumulation between control and irradiated tumors at all time points after injection. A similar trend was observed using in vivo photoacoustic imaging, which was validated by ex vivo tissue fluorescence and photoacoustic imaging. Serial quantitative radioactivity measurements of probe biodistribution further demonstrated increased probe accumulation in irradiated tumors. HQ4-DTPA has high specificity for dead cells in vivo

  11. Detection of acute inhalation injury in fire victims by means of technetium-99m DTPA radioaerosol inhalation lung scintigraphy.

    PubMed

    Lin, W Y; Kao, C H; Wang, S J

    1997-02-01

    Mortality and morbidity in fire victims are largely a function of injury due to heat and smoke. While the degree and area of burn together constitute a reliable numerical measure of cutaneous injury due to heat, as yet no satisfactory measure of inhalation injury has been developed. In this study, we employed technetium-99m diethylene triamine penta-acetic acid (DTPA) radioaerosol lung scintigraphy (inhalation scan) to evaluate acute inhalation injury in fire victims. Ten normal controls and 17 survivors from a fire accident were enrolled in the study. All patients suffered from respiratory symptoms (dyspnoea and/or cough with sputum). 99mTc-DTPA aerosol inhalation lung scintigraphy was performed in all subjects, using a commercial lung aerosol delivery unit. The degree of lung damage was presented as the clearance rate (k; %/min) calculated from the time-activity curve over the right lungs. In addition, the distribution pattern of the radioactivity in the lungs was evaluated and classified into two groups: homogeneous distribution and inhomogeneous distribution. A plain chest radiograph (CxR) and pulmonary function test (PFT) were performed in the same group of patients. The results showed that 6/17 (35.3%) patients had inhomogeneous distribution of radioactivity in their inhalation scans, and 11/17 (64.7%) had homogeneous scans. Five of the six patients with inhomogeneous scans were admitted for further management, and all patients with homogeneous scans were discharged from the emergency department and needed no further intensive care. The clearance rates of the right lung were 0.73%+/-0.13%/min for normal controls and 1.54%+/-0.58%/min for fire victims. The difference was significant, with a P value of less than 0.01. Using a cut-off value of 0.9%/min (all normal subjects were below 0. 9%/min), 14 (82.4%) patients had abnormal clearance rates of 99mTc-DTPA from the lung. In contrast, only three (17.6%) patients had abnormal CxR and three (17.6%) had abnormal

  12. Influence of Indocyanine Green on Hepatic Gd-EOB-DTPA Uptake: A Proof-of-Concept Study in Mice.

    PubMed

    Akai, Hiroyuki; Yasaka, Koichiro; Nojima, Masanori; Inoue, Yusuke; Ohtomo, Kuni; Kiryu, Shigeru

    2017-07-01

    The aim of this study was to explore the influence of indocyanine green (ICG) on hepatic uptake of gadolinium ethoxybenzyldiethylenetriaminepenta-acetic acid (Gd-EOB-DTPA). Groups of 6 female C57BL6 mice were injected with 5 mg/kg ICG, 20 mg/kg ICG, or phosphate-buffered saline (control group) 10 minutes before the injection of Gd-EOB-DTPA; identical 3-dimensional gradient echo T1-weighted images were subsequently obtained to create time-intensity curves and to measure the peak contrast ratios (CRs) of liver parenchyma. We studied both hypothermic and normothermic mice. Peak CRs for all experimental conditions were evaluated, and among-group differences were assessed using 2-way factorial analysis of variance with Bonferroni post hoc testing. In hypothermic mice, the time-intensity curves of the 3 groups gradually increased from 5 to 30 minutes and almost plateaued after 30 minutes. The peak CR decreased as the amount of injected ICG increased (control group, 5 mg/kg ICG, 20 mg/kg ICG: 1.66 ± 0.09, 1.37 ± 0.18, 1.25 ± 0.24, respectively). In normothermic animals, the time-intensity curves of the control and ICG 5 mg/kg groups peaked 10 to 15 minutes after injection, the peak CRs were very similar (control group, 5 mg/kg ICG: 2.01 ± 0.16, 1.95 ± 0.14, respectively), and the intensities thereof then gradually fell until 60 minutes. Compared with these groups, the ICG 20 mg/kg group exhibited lower peak CR (1.48 ± 0.14) and a weaker decrease in intensity to 60 minutes. Both the amount of ICG injected (P < 0.001) and the experimental temperature (P < 0.001) significantly affected the measurements. Indocyanine green inhibits the hepatic uptake of Gd-EOB-DTPA and affects the signal intensity upon Gd-EOB-DTPA-enhanced magnetic resonance imaging. Such inhibition was more obvious in hypothermic mice.

  13. Diethylenetriamine pentaacetic acid derivative of toremifene and in vitro evaluation in human breast cancer cell line MCF-7.

    PubMed

    Kilcar, Ayfer Yurt; Biber Muftuler, F Zumrut; Unak, Perihan; Avci, Cigir Biray; Gunduz, Cumhur

    2011-02-01

    Cytotoxic and apoptotic effects of toremifene-diethylenetriamine pentaacetic acid (TOR-DTPA), formed by conjugation of TOR and DTPA, on the MCF-7 cell line were evaluated. TOR-DTPA was synthesized and qualified via gas chromatography-mass spectrometry system, thin layer chromatography, and high performance liquid chromatography methods. To screen the biological properties of TOR-DTPA at determined concentrations, our ongoing effort was to evaluate apoptotic and cytotoxic effects on the MCF-7 cell line. Trypan blue dye exclusion test, XTT, ELISA, and TUNEL assays were utilized to evaluate cytotoxicity and apoptosis. TOR-DTPA has no cytotoxic and limited apoptotic effect on the MCF-7 cell line according to the results of in vitro studies. It is concluded that the lack of obvious apoptotic and cytotoxic effects allows the already proposed ligand, TOR-DTPA, to be improved as a novel hydrophilic ligand for breast imaging.

  14. Palliation of bone pain with Sn-117m(4+)DTPA

    SciTech Connect

    Atkins, L.F.; Mausner, L.F.; Meinken, G.E.

    1994-05-01

    Sn-117m(4+)DTPA prepared at Brookhaven National Laboratory has favorable physical and biological characteristics for use as a palliative agent to relieve pain from osseous metastases. The short range of the emitted conversion electrons permits large bone radiation doses without excessive radiation to the bone marrow. An accompanying 158.6 keV gamma is useful for monitoring the distribution. The T1/2 of 13.6 days provides an adequate shelf life. A previous study in humans has demonstrated favorable dosimetry with a bone surface dose of approximately 57.9 mGy/MBq and a bone surface to marrow ratio of 10:1. This study was instituted to find a dose level which was effective and to monitor effects on bone marrow. Sn-117m was administered to 14 patients. Administered activity ranged between 66 and 573 MBq or 1.2-5.8 MBq/kg body weight. At the lower dose levels (<3.1 MBq/kg, n=7), 1 obtained good relief of pain, 1 partial relief, and 1 no relief. The remaining 4 were not evaluated because of the need for further treatment of soft tissue disease or because of intervening death. The 7 patients treated at the higher dose level (4.8-5.8 MBq/kg) included patients with prostate (3), breast (3) and unknown (1) primary cancers. All patients experienced relief of pain, 5 excellent and 2 partial. No marrow suppression was observed as a result of Sn-117m therapy. Initial observations indicate that Sn-117m DTPA is effective in palliation of pain from osseous metastases without producing bone marrow suppression. Further studies at a higher dose level are planned.

  15. A Case of Enterocutaneous Fistula Diagnosed with Tc-99m DTPA Fistulography Using Hybrid SPECT/CT.

    PubMed

    Choi, Hongyoon; Paeng, Jin Chul; Chun, In Kook; Baik, Kyung Don; Kang, Keon Wook; Chung, June-Key; Lee, Dong Soo

    2012-06-01

    Enterocutaneous fistula (ECF) is a communication between the bowel lumen and the skin, which especially occurs post-operatively and is associated with significant morbidity and mortality. Correct diagnosis and anatomical information of ECF are crucial for a patient's management. Here, we present a case of ECF clearly diagnosed by hybrid single-photon emission computed tomography/computed tomography (SPECT/CT). A 61-year-old man was admitted to our hospital with persistent pus discharge from a surgical wound of previous cystectomy and ileal conduit formation. Initially, he was assessed with fistulography, and ECF was suspected by intraluminal contrast media. As clinical symptom and signs were not definitely matched with ECF, Tc-99m diethylene triamine pentaacetic acid (DTPA) SPECT/CT was performed for the evaluation of fistular tract as an alternative method. On the SPECT/CT after injection of Tc-99m DTPA to the putative fistular opening, fistular as well as intraluminal radioactivity was clearly visualized. SPECT/CT is a sensitive and safe diagnostic imaging tool for ECF.

  16. Investigations on the Ga(III) Complex of EOB-DTPA and Its 68Ga Radiolabeled Analogue.

    PubMed

    Greiser, Julia; Niksch, Tobias; Weigand, Wolfgang; Freesmeyer, Martin

    2016-08-17

    We demonstrate a method for the isolation of EOB-DTPA (3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(ethoxybenzyl)-undecanedioic acid) from its Gd(III) complex and protocols for the preparation of its novel non-radioactive, i.e., natural Ga(III) as well as radioactive (68)Ga complex. The ligand as well as the Ga(III) complex were characterized by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and elemental analysis. (68)Ga was obtained by a standard elution method from a (68)Ge/(68)Ga generator. Experiments to evaluate the (68)Ga-labeling efficiency of EOB-DTPA at pH 3.8-4.0 were performed. Established analysis techniques radio TLC (thin layer chromatography) and radio HPLC (high performance liquid chromatography) were used to determine the radiochemical purity of the tracer. As a first investigation of the (68)Ga tracers' lipophilicity the n-octanol/water distribution coefficient of (68)Ga species present in a pH 7.4 solution was determined by an extraction method. In vitro stability measurements of the tracer in various media at physiological pH were performed, revealing different rates of decomposition.

  17. Single-walled carbon nanotube-loaded doxorubicin and Gd-DTPA for targeted drug delivery and magnetic resonance imaging.

    PubMed

    Yan, Chenyu; Chen, Chengqun; Hou, Lin; Zhang, Huijuan; Che, Yingyu; Qi, Yuedong; Zhang, Xiaojian; Cheng, Jingliang; Zhang, Zhenzhong

    2017-02-01

    An aspargine-glycine-arginine (NGR) peptide modified single-walled carbon nanotubes (SWCNTs) system, developed by a simple non-covalent approach, could be loaded with the anticancer drug doxorubicin (DOX) and magnetic resonance imaging (MRI) contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). This DOX- and Gd-DTPA-loaded NGR functionalized SWCNTs (DOX/NGR-SWCNTs/Gd-DPTA) retained both cytotoxicity of DOX and MRI contrast effect of Gd-DPTA. This drug delivery system showed excellent stability in physiological solutions. This DOX/NGR-SWCNTs/Gd-DPTA system could accumulate in tumors and enter into tumor cells, which facilitated combination chemotherapy with diagnosis of tumor in one system. An excellent in vitro anti-tumor effect was shown in MCF-7 cells treated by DOX/NGR-SWCNTs/Gd-DPTA, compared with DOX solution, DOX/SWCNTs and DOX/SWCNTs/Gd-DPTA. In vivo data of DOX/NGR-SWCNTs/Gd-DPTA group in tumor-bearing mice further confirmed that this system performed much higher tumor targeting capacity and anti-tumor efficacy than other control groups.

  18. Comparison of MRI properties between derivatized DTPA and DOTA gadolinium-dendrimer conjugates

    PubMed Central

    Nwe, K.; Bernardo, M; Regino, C. A. S.; Williams, M; Brechbiel, M. W.

    2010-01-01

    In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N’,N’,N’’, N’’-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex® G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1 respectively. Molar relaxivity measured at pH 7.4, 22°C, and 3T are comparable (29.5 vs. 26.9 mM−1s−1), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t1/2 = 16 vs. 29 min.). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. PMID:20663676

  19. Preferential decorporation of americium by pulmonary administration of DTPA dry powder after inhalation of aged PuO(2) containing americium in rats.

    PubMed

    Grémy, Olivier; Tsapis, Nicolas; Chau, Quang; Renault, Daniel; Abram, Marie-Claire; Van der Meeren, Anne

    2010-11-01

    After inhalation of plutonium oxides containing various percentages of americium in rats, we identified an acellular transient pulmonary compartment, the epithelial lining fluid (ELF), in which a fraction of actinide oxides dissolve prior to absorption and subsequent extrapulmonary deposit. Chelation therapy is usually considered to be poorly efficient after inhalation of actinide oxides. However, in the present study, prompt pulmonary administration of diethylenetraminepentaacetic acid (DTPA) as a dry powder led to a decrease in actinide content in ELF together with a limitation of bone and liver deposits. Because americium is more soluble than plutonium, higher amounts of americium were found in ELF, extrapulmonary tissues and urine. Our results also demonstrated that the higher efficacy of DTPA on americium compared to plutonium in ELF induced a preferential inhibition of extrapulmonary deposit and a greater urinary excretion of americium compared to plutonium. All together, our data justify the use of an early and local DTPA treatment after inhalation of plutonium oxide aerosols in which americium can be in high proportion such as in aged compounds.

  20. Detection of urinary extravasation by delayed technetium-99m DTPA renal imaging

    SciTech Connect

    Taki, J.; Tonami, N.; Aburano, T.; Hisada, K.

    1986-08-01

    Delayed imaging with Tc-99m DTPA renal scintigraphy demonstrated urinary extravasation in a patient with acute anuria in whom early sequential imaging showed no abnormal extrarenal radionuclide accumulation.

  1. [Acellular vaccines (DTPa/dTpa) against whooping cough, protection duration].

    PubMed

    Rigo-Medrano, M Vicenta; Mendoza-García, José L; Gimeno-Gascón, Adelina; Roda-Ramón, Jorge; Cremades-Bernabeú, Israel; Antequera-Rodríguez, Pedro; Alcalá-Minagorre, Pedro J; Ortiz-de la Tabla, Victoria; Rodríguez-Díaz, Juan Carlos

    2016-01-01

    An increase in whooping cough in most of the developed countries has been detected in the last decade. To determine whether the administration of dTpa vaccine instead of DTPa fifth dose is contributing to the appearance of these cases. A descriptive study based on cases of whooping cough reported during an epidemic period in the city of Alicante in the first 5 months of 2014. Only pertussis cases confirmed by PCR were included in the study, and only those vaccinated with 5 doses were included in the analysis of the period of protection. A total of 104 cases of pertussis confirmed by PCR were reported, with 85 cases (82%) having had 5 doses of vaccine. The mean time and standard deviation (SD) of protection was 2.1±1.1 years with dTpa, and 5.1±1.5 years with DTPa (p<.001). In the protection, adjusted for age, it was observed that, after 3 years, only 47.6% of people vaccinated with dTpa were still protected, while people vaccinated with DTPa were 100% protected (P<.001). This study found that people who were properly vaccinated against pertussis and received their last re-vaccination dose with dTpa had a shorter period of protection than those who were vaccinated with DTPa. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  2. The value of Gd-EOB-DTPA-enhanced MR imaging in characterizing cirrhotic nodules with atypical enhancement on Gd-DTPA-enhanced MR images.

    PubMed

    Wang, Yi-Chun; Chou, Chen-Te; Lin, Ching-Po; Chen, Yao-Li; Chen, Yung-Fang; Chen, Ran-Chou

    2017-01-01

    To evaluate the utility of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in characterizing atypically enhanced cirrhotic nodules detected on conventional Gd-DTPA-enhanced MR images. We enrolled 61 consecutive patients with 88 atypical nodules seen on conventional Gd-DTPA-enhanced MR images who underwent Gd-EOB-DTPA-enhanced MRI within a 3-month period. Using a reference standard, we determined that 58 of the nodules were hepatocellular carcinoma (HCC) and 30 were dysplastic nodules (DNs). Tumor size, signal intensity on precontrast T1-weighted images (T1WI), T2-weighted images (T2WI) and diffusion-weighted images (DWI), and the enhancement patterns seen on dynamic phase and hepatocyte phase images were determined. There were significant differences between DNs and HCC in hyperintensity on T2WI, hypointensity on T1WI, hypervascularity on arterial phase images, typical HCC enhancement patterns on dynamic MR images, hypointensity on hepatocyte phase images, and hyperintensity on DWI. The sensitivity and specificity were 79.3% and 83.3% for T2WI, 50.0% and 80.0% for T1WI, 82.8% and 76.7% for DWI, 17.2% and 100% for dynamic MR imaging, 93.1% and 83.3% for hepatocyte phase imaging, and 46.8% and 100% when arterial hypervascularity was combined with hypointensity on hepatocyte-phase imaging. Gd-EOB-DTPA-enhanced hepatocyte phase imaging is recommended for patients at high risk for HCC who present with atypical lesions on conventional Gd-DTPA-enhanced MR images.

  3. The value of Gd-EOB-DTPA-enhanced MR imaging in characterizing cirrhotic nodules with atypical enhancement on Gd-DTPA-enhanced MR images

    PubMed Central

    Lin, Ching-Po; Chen, Yao-Li; Chen, Yung-Fang; Chen, Ran-Chou

    2017-01-01

    Purpose To evaluate the utility of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in characterizing atypically enhanced cirrhotic nodules detected on conventional Gd-DTPA-enhanced MR images. Materials and methods We enrolled 61 consecutive patients with 88 atypical nodules seen on conventional Gd-DTPA-enhanced MR images who underwent Gd-EOB-DTPA-enhanced MRI within a 3-month period. Using a reference standard, we determined that 58 of the nodules were hepatocellular carcinoma (HCC) and 30 were dysplastic nodules (DNs). Tumor size, signal intensity on precontrast T1-weighted images (T1WI), T2-weighted images (T2WI) and diffusion-weighted images (DWI), and the enhancement patterns seen on dynamic phase and hepatocyte phase images were determined. Results There were significant differences between DNs and HCC in hyperintensity on T2WI, hypointensity on T1WI, hypervascularity on arterial phase images, typical HCC enhancement patterns on dynamic MR images, hypointensity on hepatocyte phase images, and hyperintensity on DWI. The sensitivity and specificity were 79.3% and 83.3% for T2WI, 50.0% and 80.0% for T1WI, 82.8% and 76.7% for DWI, 17.2% and 100% for dynamic MR imaging, 93.1% and 83.3% for hepatocyte phase imaging, and 46.8% and 100% when arterial hypervascularity was combined with hypointensity on hepatocyte-phase imaging. Conclusion Gd-EOB-DTPA-enhanced hepatocyte phase imaging is recommended for patients at high risk for HCC who present with atypical lesions on conventional Gd-DTPA-enhanced MR images. PMID:28355258

  4. Induction of sister chromatid exchange in the presence of gadolinium-DTPA and its reduction by dimethyl sulfoxide

    SciTech Connect

    Yamazaki, Etsuo; Fukuda, Hozumi; Shibuya, Hitoshi; Matsubara, Sho

    1996-05-01

    The authors investigate the frequency of sister chromatid exchange (SCE) after the addition of gadolinium (Gd)-DTPA to venous blood samples. Venous blood was obtained from nonsmokers. Samples were incubated with Gd-DTPA alone or in combination with mitomycin C, cytarabine, and dimethyl sulfoxide (DMSO), and then evaluated for SCEs. The frequency of SCE increased with the concentration of Gd-DTPA and as each chemotherapeutic agent was added. Sister chromatid exchange frequencies were lower when the blood was treated with a combination of Gd-DTPA and DMSO compared with Gd-DTPA alone. The increase in frequency of SCE seen after the addition of Gd-DTPA was decreased by the addition of DMSO, indicating the production of hydroxyl radicals. The effect likely is dissociation-related. 14 refs., 6 tabs.

  5. Design and functionalities of the MADOR® software suite for dose-reduction management after DTPA therapy.

    PubMed

    Leprince, B; Fritsch, P; Bérard, P; Roméo, P-H

    2016-03-01

    A software suite on biokinetics of radionuclides and internal dosimetry intended for the occupational health practitioners of nuclear industry and for expert opinions has been developed under Borland C++ Builder™. These computing tools allow physicians to improve the dosimetric follow-up of workers in agreement with the French regulations and to manage new internal contaminations by radionuclides such as Pu and/or Am after diethylene triamine penta-acetic acid treatments. In this paper, the concept and functionalities of the first two computing tools of this MADOR(®) suite are described. The release 0.0 is the forensic application, which allows calculating the derived recording levels for intake by inhalation or ingestion of the main radioisotopes encountered in occupational environment. Indeed, these reference values of activity are convenient to interpret rapidly the bioassay measurements and make decisions as part of medical monitoring. The release 1.0 addresses the effect of DTPA treatments on Pu/Am biokinetics and the dose benefit. The forensic results of the MADOR(®) suite were validated by comparison with reference data. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Prolonged local retention of subcutaneously injected polymers monitored by noninvasive SPECT imaging.

    PubMed

    Kojima, Chie; Niki, Yuichiro; Ogawa, Mikako; Magata, Yasuhiro

    2014-12-10

    Polymers are widely applied to drug delivery systems because polymers are generally excreted from the body more slowly than small molecules. Subcutaneous injection is one plausible means of administration. In this study, the in vivo behaviors of subcutaneously injected polymers, linear poly(glutamic acid) (Poly-Glu), acetylated dendrimer (Ac-den) and collagen peptide-conjugated dendrimer (CP-den), were investigated. Single photon emission computed tomography (SPECT) imaging was used to noninvasively monitor the in vivo behaviors. Diethylenetriaminepentaacetic acid (DTPA) was conjugated to these polymers, which were labeled with radioactive (111)In. These (111)In-DTPA-bearing polymers (Poly-Glu-DTPA, Ac-den-DTPA and CP-den-DTPA) and unconjugated DTPA were subcutaneously injected into tumor-bearing mice, which were subjected to SPECT imaging. These (111)In-DTPA-bearing polymers were largely retained at the injection site for at least 1 day, whereas the unconjugated DTPA was rapidly cleared from the whole body through excretion. Poly-Glu-DTPA and Ac-den-DTPA were partly accumulated in the kidney (and the liver), but the CP-den-DTPA was not. However, these (111)In-DTPA-bearing polymers were accumulated in the liver and the kidney following intravenous administration. These results indicate that the subcutaneously injected polymers did not largely gain substantial access to the systemic circulation, which is useful for a depot of drug around the injection site.

  7. An efficient optical-electrochemical dual probe for highly sensitive recognition of dopamine based on terbium complex functionalized reduced graphene oxide.

    PubMed

    Zhou, Zhan; Wang, Qianming

    2014-05-07

    A novel organic-inorganic hybrid sensor based on diethylenetriaminepentaacetic acid (DTPA) modified reduced graphene oxide (RGO-DTPA) chelated with terbium ions allows detection of dopamine (DA) through an emission enhancement effect. Its luminescence, peaking at 545 nm, has been improved by a factor of 25 in the presence of DA (detection limit = 80 nM). In addition, this covalently bonded terbium complex functionalized reduced graphene oxide (RGO-DTPA-Tb) can be successfully assembled on a glassy carbon electrode. The assay performed through differential pulse voltammetry (DPV) yielded obvious peak separation between DA and excessive amounts of the interfering ascorbic acid (AA).

  8. A Drug-Repositioning Screening Identifies Pentetic Acid as a Potential Therapeutic Agent for Suppressing the Elastase-Mediated Virulence of Pseudomonas aeruginosa

    PubMed Central

    Gi, Mia; Jeong, Junhui; Lee, Keehoon; Lee, Kang-Mu; Toyofuku, Masanori; Yong, Dong Eun

    2014-01-01

    Pseudomonas aeruginosa, a Gram-negative bacterium of clinical significance, produces elastase as a predominant exoprotease. Here, we screened a library of chemical compounds currently used for human medication and identified diethylene triamine penta-acetic acid (DTPA, pentetic acid) as an agent that suppresses the production of elastase. Elastase activity found in the prototype P. aeruginosa strain PAO1 was significantly decreased when grown with a concentration as low as 20 μM DTPA. Supplementation with Zn2+ or Mn2+ ions restored the suppressive effect of DTPA, suggesting that the DTPA-mediated decrease in elastase activity is associated with ion-chelating activity. In DTPA-treated PAO1 cells, transcription of the elastase-encoding lasB gene and levels of the Pseudomonas quinolone signal (PQS), a molecule that mediates P. aeruginosa quorum sensing (QS), were significantly downregulated, reflecting the potential involvement of the PQS QS system in DTPA-mediated elastase suppression. Biofilm formation was also decreased by DTPA treatment. When A549 alveolar type II-like adenocarcinoma cells were infected with PAO1 cells in the presence of DTPA, A549 cell viability was substantially increased. Furthermore, the intranasal delivery of DTPA to PAO1-infected mice alleviated the pathogenic effects of PAO1 cells in the animals. Together, our results revealed a novel function for a known molecule that may help treat P. aeruginosa airway infection. PMID:25246397

  9. A drug-repositioning screening identifies pentetic acid as a potential therapeutic agent for suppressing the elastase-mediated virulence of Pseudomonas aeruginosa.

    PubMed

    Gi, Mia; Jeong, Junhui; Lee, Keehoon; Lee, Kang-Mu; Toyofuku, Masanori; Yong, Dong Eun; Yoon, Sang Sun; Choi, Jae Young

    2014-12-01

    Pseudomonas aeruginosa, a Gram-negative bacterium of clinical significance, produces elastase as a predominant exoprotease. Here, we screened a library of chemical compounds currently used for human medication and identified diethylene triamine penta-acetic acid (DTPA, pentetic acid) as an agent that suppresses the production of elastase. Elastase activity found in the prototype P. aeruginosa strain PAO1 was significantly decreased when grown with a concentration as low as 20 μM DTPA. Supplementation with Zn(2+) or Mn(2+) ions restored the suppressive effect of DTPA, suggesting that the DTPA-mediated decrease in elastase activity is associated with ion-chelating activity. In DTPA-treated PAO1 cells, transcription of the elastase-encoding lasB gene and levels of the Pseudomonas quinolone signal (PQS), a molecule that mediates P. aeruginosa quorum sensing (QS), were significantly downregulated, reflecting the potential involvement of the PQS QS system in DTPA-mediated elastase suppression. Biofilm formation was also decreased by DTPA treatment. When A549 alveolar type II-like adenocarcinoma cells were infected with PAO1 cells in the presence of DTPA, A549 cell viability was substantially increased. Furthermore, the intranasal delivery of DTPA to PAO1-infected mice alleviated the pathogenic effects of PAO1 cells in the animals. Together, our results revealed a novel function for a known molecule that may help treat P. aeruginosa airway infection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. Quantitative measurement of regional blood flow with gadolinium diethylenetriaminepentaacetate bolus track NMR imaging in cerebral infarcts in rats: validation with the iodo[14C]antipyrine technique.

    PubMed Central

    Wittlich, F; Kohno, K; Mies, G; Norris, D G; Hoehn-Berlage, M

    1995-01-01

    NMR bolus track measurements were correlated with autoradiographically determined regional cerebral blood flow (rCBF). The NMR method is based on bolus infusion of the contrast agent gadolinium diethylenetriaminepentaacetate and high-speed T*2-sensitive NMR imaging. The first pass of the contrast agent through the image plane causes a transient decrease of the signal intensity. This time course of the signal intensity is transformed into relative concentrations of the contrast agent in each pixel. The mean transit time and relative blood flow and volume are calculated from such indicator dilution curves. We investigated whether this NMR technique correctly expresses the relative rCBF. The relative blood flow data, calculated from NMR bolus track experiments, and the absolute values of iodo[14C]antipyrine autoradiography were compared. A linear relationship was observed, indicating the proportionality of the transient NMR signal change with CBF. Excellent interindividual reproducibility of calibration constants is observed (r = 0.963). For a given NMR protocol, bolus track measurements calibrated with autoradiography after the experiment allow determination of absolute values for rCBF and regional blood volume. Images Fig. 2 Fig. 3 PMID:7892189

  11. Dual pathway clearance of /sup 99m/Tc-DTPA from the bronchial mucosa

    SciTech Connect

    Bennett, W.D.; Ilowite, J.S.

    1989-05-01

    Many studies have reported clearance rates of 99mTc-DTPA from the alveolar epithelial surface, but few have measured clearance of this solute from the bronchial mucosa. Those that have attempted such measurements have discounted the possibility that 99mTc-DTPA may be removed from the bronchial airways by mucocilliary transport as well as by absorption through the epithelium. This study was designed to better approximate the rate of 99mTc-DTPA absorption across the bronchial epithelium by correcting the measurements of total 99mTc-DTPA clearance for mucus transport. On two separate study days, each normal, nonsmoking subject (n = 8) breathed an aqueous aerosol (2.0 microns MMAD, sigma g = 2.0) containing 99mTc bound to DTPA or human serum ablumin (HSA) (a relatively nonpermeable solute that is cleared only by mucus transport over the period of measured clearance) while seated in front of a gamma camera. Breathing pattern was standardized to produce a similar central deposition of particles on both study days. From measurements of retention versus time over a 1-h period, exponential rate constants (Ktot and Km) were determined for the clearance of 99mTc-DTPA and 99mTc-HSA, respectively. By modeling the airways as a single compartment with two possible routes of clearance, we determined the permeability rate constant, Kp, as Ktot minus Km. Results showed that mucus clearance (Km) accounted for two thirds of the total rate of 99mTc-DTPA clearance (Ktot) (mean Ktot = 0.00985, Km = 0.00698, and Kp = 0.00287/min).

  12. Decorporation approach following rat lung contamination with a moderately soluble compound of plutonium using local and systemic Ca-DTPA combined chelation.

    PubMed

    Grémy, Olivier; Tsapis, Nicolas; Bruel, Sylvie; Renault, Daniel; Van der Meeren, Anne

    2012-09-01

    Decorporation efficacy of prompt pulmonary delivery of DTPA dry powder was assessed following lung contamination with plutonium nitrate and compared to an intravenous injection of DTPA solution and a combined administration of both DTPA compounds. In addition, efficacy of a delayed treatment was assessed. In case of either early or late administration, insufflated DTPA was more efficient than intravenously injected DTPA in reducing the plutonium lung burden due to its high local concentration. Prompt treatment with DTPA powder was also more effective in limiting extrapulmonary deposits by removing the early transportable fraction of plutonium from lungs prior its absorption into blood. Translocation of DTPA from lungs to blood may also contribute to the decrease in extrapulmonary retention, as shown by reduced liver deposit after delayed pulmonary administration of DTPA. Efficacy of DTPA dry powder was further increased by the combined intravenous administration of DTPA solution for reducing extrapulmonary deposits of plutonium and promoting its urinary excretion. According to our results, the most effective treatment protocol for plutonium decorporation was the early pulmonary delivery of DTPA powder supplemented by an intravenous injection of DTPA solution. Following inhalation of plutonium as nitrate chemical form, this combined chelation therapy should provide a more effective method of treatment than conventional intravenous injection alone. At later stages following lung contamination, pulmonary administration of DTPA should also be considered as the treatment of choice for decreasing the lung burden.

  13. Simplified structure of a new model to describe urinary excretion of plutonium after systemic, liver or pulmonary contamination of rats associated with Ca-DTPA treatments.

    PubMed

    Fritsch, P; Sérandour, A L; Grémy, O; Phan, G; Tsapis, N; Abram, M C; Renault, D; Fattal, E; Benech, H; Deverre, J R; Poncy, J L

    2009-06-01

    This study validates, by targeted experiments, several modeling hypotheses for interpretation of urinary excretion of plutonium after Ca-DTPA treatments. Different formulations and doses of Ca-DTPA were administered to rats before or after systemic, liver or lung contamination with various chemical forms of plutonium. The biokinetics of plutonium was also characterized after i.v. injection of Pu-DTPA. Once formed, Pu-DTPA complexes are stable in most biological environments. Pu-DTPA present in circulating fluids is rapidly excreted in the urine, but 2-3% is retained, mainly in soft tissues, and is then excreted slowly in the urine after transfer to blood. Potentially, all intracellular monoatomic forms of plutonium could be decorporated after DTPA internalization involving slow urinary excretion of Pu-DTPA with half-lives varying from 2.5 to 6 days as a function of tissue retention. The ratio of fast to slow urinary excretion of Pu-DTPA depends on both plutonium contamination and Ca-DTPA treatment. Fast urinary excretion of Pu-DTPA corresponds to extracellular decorporation that occurs beyond a threshold of the free DTPA concentration in circulating fluids. Slow excretion corresponds mostly to intracellular decorporation and depends on the amount of intracellular DTPA. From these results, the structure of a simplified model is proposed for interpretation of data obtained with Ca-DTPA treatments after systemic, wound or pulmonary contamination by plutonium.

  14. Folate-PEG-CKK(2)-DTPA, A Potential Carrier for Lymph-Metastasized Tumor Targeting.

    PubMed

    Gu, Bing; Xie, Cao; Zhu, Jianhua; He, Wei; Lu, Weiyue

    2010-05-01

    A novel conjugate, Folate-PEG-CKK(2)-DTPA, was designed and prepared as a carrier for lymphatic metastasized tumor imaging diagnosis and targeting therapy. Folate-PEG-CKK(2)-DTPA was synthesized and characterized by analysis High Performance Liquid Chromatography, Size Exclusive Chromatography and (1)H-NMR. (99m)Tc-labeled conjugation was prepared, and in vivo quantitative biodistribution and SPECT imaging were studied after subcutaneously injected into the rats and rabbits, respectively. Cell uptake study was carried in a KB cell line using fluorescent methods. In vivo and ex vivo fluorescent imaging study was carried in tumor-bearing nude mouse to evaluate its targeting ability. Folate-PEG-CKK(2)-DTPA was synthesized with high purity. Both in vivo biodistribution study and SPECT imaging study show the rapid direction and high distribution of the conjugation to the lymph nodes. The uptake of fluorescence-labeled Folate-PEG-CKK(2)-DTPA in human oral epidermis carcinoma cells was observed. In vivo and ex vivo fluorescent imaging study indicated it could accumulate in tumor region after vein tail injection in nude mouse. All these findings suggested Folate-PEG-CKK(2)-DTPA as a novel and dependable carrier for tumor diagnosis and therapy, especially for lymph-metastasized tumors.

  15. Spatial variability of soil total and DTPA-extractable cadmium caused by long-term application of phosphate fertilizers, crop rotation, and soil characteristics.

    PubMed

    Jafarnejadi, A R; Sayyad, Gh; Homaee, M; Davamei, A H

    2013-05-01

    Increasing cadmium (Cd) accumulation in agricultural soils is undesirable due to its hazardous influences on human health. Thus, having more information on spatial variability of Cd and factors effective to increase its content on the cultivated soils is very important. Phosphate fertilizers are main contamination source of cadmium (Cd) in cultivated soils. Also, crop rotation is a critical management practice which can alter soil Cd content. This study was conducted to evaluate the effects of long-term consumption of the phosphate fertilizers, crop rotations, and soil characteristics on spatial variability of two soil Cd species (i.e., total and diethylene triamine pentaacetic acid (DTPA) extractable) in agricultural soils. The study was conducted in wheat farms of Khuzestan Province, Iran. Long-term (27-year period (1980 to 2006)) data including the rate and the type of phosphate fertilizers application, the respective area, and the rotation type of different regions were used. Afterwards, soil Cd content (total or DTPA extractable) and its spatial variability in study area (400,000 ha) were determined by sampling from soils of 255 fields. The results showed that the consumption rate of di-ammonium phosphate fertilizer have been varied enormously in the period study. The application rate of phosphorus fertilizers was very high in some subregions with have extensive agricultural activities (more than 95 kg/ha). The average and maximum contents of total Cd in the study region were obtained as 1.47 and 2.19 mg/kg and DTPA-extractable Cd as 0.084 and 0.35 mg/kg, respectively. The spatial variability of Cd indicated that total and DTPA-extractable Cd contents were over 0.8 and 0.1 mg/kg in 95 and 25 % of samples, respectively. The spherical model enjoys the best fitting and lowest error rate to appraise the Cd content. Comparing the phosphate fertilizer consumption rate with spatial variability of the soil cadmium (both total and DTPA extractable) revealed the high

  16. Gd-EOB-DTPA-enhanced 3.0-Tesla MRI findings for the preoperative detection of focal liver lesions: Comparison with iodine-enhanced multi-detector computed tomography

    NASA Astrophysics Data System (ADS)

    Park, Hyong-Hu; Goo, Eun-Hoe; Im, In-Chul; Lee, Jae-Seung; Kim, Moon-Jib; Kwak, Byung-Joon; Chung, Woon-Kwan; Dong, Kyung-Rae

    2012-12-01

    The safety of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid (Gd-EOB-DTPA) has been confirmed, but more study is needed to assess the diagnostic accuracy of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in patients with a hepatocellular carcinoma (HCC) for whom surgical treatment is considered or with a metastatic hepatoma. Research is also needed to examine the rate of detection of hepatic lesions compared to multi-detector computed tomography (MDCT), which is used most frequently to localize and characterize a HCC. Gd-EOB-DTPA-enhanced MRI and iodine-enhanced MDCT imaging were compared for the preoperative detection of focal liver lesions. The clinical usefulness of each method was examined. The current study enrolled 79 patients with focal liver lesions who preoperatively underwent MRI and MDCT. In these patients, there was less than one month between the two diagnostic modalities. Imaging data were taken before and after contrast enhancement in both methods. To evaluate the images, we analyzed the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) in the lesions and the liver parenchyma. To compare the sensitivity of the two methods, we performed a quantitative analysis of the percentage signal intensity of the liver (PSIL) on a high resolution picture archiving and communication system (PACS) monitor (paired-samples t-test, p < 0.05). The enhancement was evaluated based on a consensus of four observers. The enhancement pattern and the morphological features during the arterial and the delayed phases were correlated between the Gd-EOB-DTPA-enhanced MRI findings and the iodine-enhanced MDCT by using an adjusted x2 test. The SNRs, CNRs, and PSIL all had a greater detection rate in Gd-EOB-DTPA enhanced MRI than in iodine-enhanced MDCT. Hepatocyte-selective uptake was observed 20 minutes after the injection in the focal nodular hyperplasia (FNH, 9/9), adenoma (9/10), and highly-differentiated HCC (grade G1, 27/30). Rim

  17. Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.

    PubMed

    Gupta, Abhishek; de Campo, Liliana; Rehmanjan, Beenish; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

    2015-02-03

    Supramolecular self-assembling amphiphiles have been widely used in drug delivery and diagnostic imaging. In this report, we present the self-assembly of Gd (III) chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various compositions. The dispersed colloidal nanoassemblies were evaluated as potential MRI contrast agents at various magnetic field strengths. The homogeneous incorporation of Gd-DTPA-MP in PT was confirmed by polarized optical microscopy (POM) and synchrotron small-angle X-ray scattering (SAXS) of the bulk phases of the mixtures. The liquid crystalline nanostructures, morphology, and the size distribution of the nanoassemblies were studied by SAXS, cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The dispersions with up to 2 mol % of Gd-DTPA-MP in PT retained inverse cubosomal nanoassemblies, whereas the rest of the dispersions transformed to liposomal nanoassemblies. In vitro relaxivity studies were performed on all the dispersions at 0.54, 9.40, and 11.74 T and compared to Magnevist, a commercially available contrast agent. All the dispersions showed much higher relaxivities compared to Magnevist at both low and high magnetic field strengths. Image contrast of the nanoassemblies was also found to be much better than Magnevist at the same Gd concentration at 11.74 T. Moreover, the Gd-DTPA-MP/PT dispersions showed improved relaxivities over the pure Gd-DTPA-MP dispersion at high magnetic fields. These stable colloidal nanoassemblies have high potential to be used as combined delivery matrices for diagnostics and therapeutics.

  18. Gd-EOB-DTPA-Enhanced MR Imaging of the Liver: The Effect on T2 Relaxation Times and Apparent Diffusion Coefficient (ADC)

    PubMed Central

    Cieszanowski, Andrzej; Podgórska, Joanna; Rosiak, Grzegorz; Maj, Edyta; Grudziński, Ireneusz P.; Kaczyński, Bartosz; Szeszkowski, Wojciech; Milczarek, Krzysztof; Rowiński, Olgierd

    2016-01-01

    Summary Background To investigate the effect of gadoxetic acid disodium (Gd-EOB-DTPA) on T2 relaxation times and apparent diffusion coefficient (ADC) values of the liver and focal liver lesions on a 1.5-T system. Material/Methods Magnetic resonance (MR) studies of 50 patients with 35 liver lesions were retrospectively analyzed. All examinations were performed at 1.5T and included T2-weighted turbo spin-echo (TSE) and diffusion-weighted (DW) images acquired before and after intravenous administration of Gd-EOB-DTPA. To assess the effect of this hepatobiliary contrast agent on T2-weighted TSE images and DW images T2 relaxation times and ADC values of the liver and FLLs were calculated and compared pre- and post-injection. Results The mean T2 relaxation times of the liver and focal hepatic lesions were lower on enhanced than on unenhanced T2-weighted TSE images (decrease of 2.7% and 3.6% respectively), although these differences were not statistically significant. The mean ADC values of the liver showed statistically significant decrease (of 4.6%) on contrast-enhanced DW images, compared to unenhanced images (P>0.05). The mean ADC value of liver lesions was lower on enhanced than on unenhanced DW images, but this difference (of 2.9%) did not reach statistical significance. Conclusions The mean T2 relaxation times of the liver and focal liver lesions as well as the mean ADC values of liver lesions were not significantly different before and after administration of Gd-EOB-DTPA. Therefore, acquisition of T2-weighted and DW images between the dynamic contrast-enhanced examination and hepatobiliary phase is feasible and time-saving. PMID:27026795

  19. Technetium-99m DTPA aerosol and gallium scanning in acquired immune deficiency syndrome

    SciTech Connect

    Picard, C.; Meignan, M.; Rosso, J.; Cinotti, L.; Mayaud, C.; Revuz, J.

    1987-07-01

    In 11 non-smoking AIDS patients suspected of pneumocystis carinii pneumonia (PCP), the results of Tc-99m DTPA aerosol clearances, gallium scans, and arterial blood gases were compared with those of bronchoalveolar lavage (BAL). Nine patients had PCP. All had increased clearances five times higher than the normal (5.6 +/- 2.3% X min-1 vs 1.1 +/- 0.34% X min-1, N = 10, P less than 0.001), suggesting an increased alveolar permeability. Gallium scans were abnormal in six patients but normal or slightly abnormal in the three others. Four of these nine patients had normal chest x-rays. In two of these the gallium scan was abnormal, but in the two others, only the increased Tc-99m DTPA clearances showed evidence of lung disease. Two patients had normal BAL, with normal clearances and gallium scans. Four out of the nine patients with PCP were studied after treatment. Three recovered and had normal clearance and gallium scans. One still had PCP with increased clearance but normal gallium scan. Gallium scanning and Tc-99m DTPA clearance are useful for detecting lung disease in AIDS patients with suspected PCP and for prompting BAL when chest x-rays and PaO/sub 2/ levels are normal. Due to its high sensitivity, a normal Tc-99m DTPA clearance could avoid BAL.

  20. Vesicoureteral Reflux Detected with 99mTc-DTPA Renal Scintigraphy during Evaluation of Renal Function

    PubMed Central

    Manevska, Nevena; Stojanoski, Sinisa; Majstorov, Venjamin; Pop-Gjorcheva, Daniela; Zdraveska, Nikolina; Kuzmanovska, Dafina

    2016-01-01

    BACKGROUND: Radionuclide techniques, as direct radionuclide cystography and 99mTc-DMSA scintigraphy, have been used in evaluation of vesicoureteral reflux (VUR) and reflux nephropathy (RN) in children. Dynamic 99mTc-DTPA scintigraphy is reserved for evaluation of differential renal function and obstruction in children, where hydronephrosis is detected by ultrasonography (US) pre- or postnatally. CASE REPORT: Six year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal, severe bilateral VUR was detected by voiding urethrocytography. US and 99mTc-DTPA scintigraphy performed in the first month of life showed small left kidney that participated with 2% in the global renal function. Bilateral cutaneous ureterostomy has been performed in order to obtain good renal drainage and promote optimal renal growth. Twelve months later, classic antireflux procedure was done. Control 99mTc-DTPA scintigraphy, 5 ys after antireflux surgery, revealed persisting radioactivity during the diuretic phase, in the left kidney that indicated antireflux procedure failure with VUR reappearance. CONCLUSION: 99mTc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography when rising of radioactivity in the kidney region, during the diuretic phase can indicate presence of VUR. PMID:27275347

  1. Treatment of actinide exposures: a review of Ca-DTPA injections inside CEA-COGEMA plants.

    PubMed

    Grappin, Louise; Berard, Philippe; Menetrier, Florence; Carbone, Lise; Courtay, Catherine; Castagnet, Xavier; Le Goff, Jean-Pierre; Neron, Marie-Odile; Piechowski, Jean

    2007-01-01

    Calcium diethylenetriamine pentacetate (Ca-DTPA) has been used for medical treatment of plutonium and americium contaminations in the CEA and COGEMA plants from 1970 to 2003. This paper is a survey of the injections Ca-DTPA administered as a chelating molecule and it will be a part of the authorisation process for Ca-DTPA by intravenous administration. Out of 1158 injections administered to 469 persons, 548 events of possible or confirmed contamination were reported. These employees were followed by occupational physicians according to the current French regulations. These incidents took place at work, were most often minor, not requiring follow-up treatment. The authors present (1) a synthesis of the most recent findings. Due to its short biological half-time and its limited action in the blood, Ca-DTPA does not chelate with plutonium and americium as soon as these elements are deposited in the target organs. It justifies an early treatment, even in cases of suspected contamination followed by additional injections if necessary (2) data concerning these 1158 injections (route of contamination, dosage, adverse effects, etc.) The authors also investigated a study on the efficacy of the product on a group of persons having received five or more injections. These results were compared with the efficacy estimated theoretically. Dosages and therapeutic schemes were proposed based on these observations. This synthesis is the result of a collective work having mobilised the occupational medicine departments, the medical laboratories inside a working group CEA-COGEMA-SPRA.

  2. The half maximum time of (99m)Tc-DTPA renography measured in healthy kidney donors, compared to (131)I-OIH.

    PubMed

    Cheng, Bing; Ding, Xianmin; Du, Xiaoguang; Xie, Xinli; Han, Xinmin; Liu, Baoping

    2011-01-01

    Technetium-99m-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) has been widely used after (131)I-ortho-hippurate ((131)I-OIH) for renography and to test renal function. Only a few reports refer to normal values range of (99m)Tc-DTPA renography half maximum time (HMT). We have measured the normal value range of (99m)Tc-DTPA renography HMT in our department, of 433 healthy kidney donors from 2007 to 2010, and compared these results with those of (131)I-OIH renography. There were 326 men and 107 women, 18y-69y (median age 29y), subjects were measured before the donation of their kidneys operation and their biochemical, ultrasound and renal function tests were normal. All subjects drunk at least 1 litre of tap water before renography. The (99m)Tc-DTPA dynamic scintigraphy was performed in the posterior view by injecting intravenously as a bolus 185-296MBq. Dynamic imaging was performed immediately after the injection, using a high-resolution low-energy general purpose collimator and a large field of view dual-detector gamma-camera (Hawkeye; General Electric Medical Systems, USA). Matrix was 64Χ64, the phase acquisition time of blood perfusion was 1s/frame and 30 frames were collected. Dynamic acquisition was 30s/frame and 39 frames were collected. Total acquisition time was 20min. We defined as background two regions of interest around the kidneys and the aorta, for radioactive decay correction. We also compared (99m)Tc-DTPA renography HMT values with the HMT values of (131)I-OIH, between the two kidneys, and between men and women. The findings were evaluated by using frequency distribution analysis, paired Sample Student's t-test and one sample t test, with a level of significance P<0.05. We used the SPSS 10.0 statistical software. Since values beyond a high boundary were regarded as unusual, we used the P(95), i.e. " 95% of HMT reference ranges value" to determine the medical reference range of values, as the HMT normal limit. This reference value is used

  3. Pharmacokinetics of DTPA entrapped in conventional and long-circulating liposomes of different size for plutonium decorporation.

    PubMed

    Phan, Guillaume; Herbet, Amaury; Cholet, Sophie; Benech, Henri; Deverre, Jean-Robert; Fattal, Elias

    2005-12-10

    The aim of the present study was to develop an efficient DTPA liposome formulation designed for plutonium decorporation. DTPA was encapsulated in conventional (CL) and polyethylene glycol-coated stealth liposomes (SL) prepared by extrusion followed by the freeze-thawing method and sizing from around 100 to 800 nm. DTPA encapsulation percentages were approximately 30% in CL of any size but dropped from 48% to 7% as the diameter of SL was reduced. The pharmacokinetics of [(14)C]-DTPA encapsulated in large and small vesicles was evaluated in rats after a single intravenous administration. Both liposomal composition and size reduction had a significant impact on pharmacokinetic parameters, inducing a marked increased in exposure of the body to DTPA and its delayed excretion. DTPA distribution was moderate in liver but enhanced in spleen and bone and was dose-dependent, especially when SL of 100 nm were given. In conclusion, small and stealth(R) vesicles have interesting properties in delivering DTPA to contaminated tissues.

  4. Therapy using labelled somatostatin analogues: comparison of the absorbed doses with 111In-DTPA-D-Phe1-octreotide and yttrium-labelled DOTA-D-Phe1-Tyr3-octreotide.

    PubMed

    Barone, Raffaella; Walrand, Stéphan; Konijnenberg, Mark; Valkema, Roelf; Kvols, Larry K; Krenning, Eric P; Pauwels, Stanislas; Jamar, François

    2008-03-01

    We estimated the absorbed doses for (111)In-DTPA-D-Phe(1)-octreotide and (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide in the same patients in order to compare the potential effectiveness (tumour dose) and safety (kidney and red marrow dose) of these drugs for peptide-targeted radiotherapy of somatostatin receptor positive tumours. Six patients with neuroendocrine tumours underwent quantitative (111)In-DTPA-D-Phe(1)-octreotide SPECT and (86)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scan at intervals of 1 week. All studies were performed with a co-infusion of amino acids for renal protection. PET and SPECT were reconstructed using iterative algorithms, incorporating attenuation and scatter corrections. Tissue uptakes (IA%) were measured and used to calculate residence times. Absorbed doses to tissues were estimated and the maximal allowed activity, defined as either the activity delivering 23 Gy to the kidneys (MAA(K)) or 2 Gy to the red marrow (MAA(RM)), was calculated and the resulting tumour absorbed doses were computed. For the MAA(K) the mean absorbed dose to the red marrow was lower for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (1.8+/-0.9 Gy vs. 6.4+/-1.6 Gy; P<0.001). The median absorbed dose to tumours for the MAA(K) was two-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide as compared to (111)In-DTPA-D-Phe(1)-octreotide (30.1 vs. 12.6 Gy; P<0.05). The median absorbed dose to tumours estimated for the MAA(RM) was 10-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (35.1 Gy vs. 3.9 Gy; P<0.05). This direct intra-patient comparison confirms that the use of (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide is more appropriate for therapy of somatostatin receptor bearing tumours. When using (111)In-DTPA-D-Phe(1)-octreotide, the red marrow represents the major critical organ; this can result in significant toxicity if high activities have to be administered to obtain efficient tumour irradiation.

  5. Self-Assembled Monolayers of Dithiophosphinic Acids on Gold

    NASA Astrophysics Data System (ADS)

    San Juan, Ronan Roca

    This dissertation reports the synthesis of derivatives of dithiophosphinic acids (R1R2DTPAs), and the formation and characterization of DTPA SAMs on gold to build a knowledge base on their nature of binding, organization of the alkyl chains and electrochemical barrier properties. The binding of DTPA molecules on gold depends on the morphology of the gold film: They bind in a mixed monodentate and bidentate modes on standard as-deposited (As-Dep) gold, while they fully chelate on smoother template-stripped (TS) gold. Chapter 2 focuses on van der Waals interactions of various alkyl chain lengths of symmetrical R2DTPA SAMs, which increase with increasing chain lengths similar to those of the analogous n-alkanethiol SAMs, but with alkyl chains that are generally less dense than those of n-alkanethiol SAMs. Chapter 3 addresses why the DTPA compounds do not chelate on the standard As-Dep gold by comparing (C16)2DTPA SAM to (C16 )2DDP SAM. Here, side chain crystallinity stabilizes DTPA SAM structure at the expense of chelation of the DTPA molecules, which leads to a mixture of bidentate and monodentate DTPA molecules, whereas the increased flexibility of the chains in DDP due to the oxygen atoms retains chelation of the DDP molecules. Chapter 4 focuses on the SAMs formed from RlongRshort DTPAs, which shows that the length of the short chain spacer affects SAM packing density and thickness. The SAMs of these molecules also show homogeneous mixing of Rlong and Rshort chains. Chapter 5 investigates PhRDTPA SAMs in preparation for molecular junction studies. The chelation of PhRDTPA molecules on TS gold allows the PhRDTPAs to act as molecular alligator clips. The length of the alkyl chains controls the density of the phenyl group and they fill in the voids between adsorbates to prevent electrical shorting. Finally, Chapter 6 incorporates OH tail group(s) to control the wettability of DTPA SAMs. The presence of OH groups in DTPAs forms hydrophilic SAMs. The symmetrical OH

  6. Synthesis and characterization of new low-molecular-weight lysine-conjugated Gd-DTPA contrast agents.

    PubMed

    Laurent, Sophie; Burtea, Carmen; Vander Elst, Luce; Muller, Robert N

    2011-01-01

    Various blood pool contrast agents (CAs), characterized by intravascular distribution, have been developed to assist contrast enhanced magnetic resonance angiography (MRA). Among these CAs, the DTPA derivatives conjugated to synthetic polypeptides, such as polylysine, represent attractive candidates for blood pool imaging. However, due to the presence of charged residues located on their backbone, these agents are retained in the kidneys and this compromises their long blood half-life. In order to overcome this major drawback of the polylysine compounds, two new low-molecular-weight CAs were synthesized in the present work by conjugating four or six 1-p-isothiocyanatobenzyl-DTPA moieties to tri- or penta-Lys peptides [(Gd-DTPA)(4) Lys(3) and (Gd-DTPA)(6) Lys(5)], respectively. All the -NH(2) groups of Lys were thus blocked by covalent conjugation to DTPA. The stability and relaxometric properties of these compounds, as well as their pharmacokinetic and biodistribution characteristics, were then evaluated. The half-life in blood of these new polylysine derivatives, as determined in rats, is twofold longer than that of Gd-DTPA. The compounds could thus be optimal blood pool markers for MRA, which typically uses fast acquisition times. The absence of positive molecular charge did not limit their retention in kidneys 2 h after administration. On the other hand, (Gd-DTPA)(4) Lys(3) is retained in kidneys to a lesser extent than (Gd-DTPA)(6) Lys(5) . Their moderate retention in blood and their higher stability and relaxivity in comparison with Gd-DTPA highlight these polylysine derivatives as optimal compared with previously developed polylysine compounds. Copyright © 2010 John Wiley & Sons, Ltd.

  7. Optimization of Gd-DTPA-enhanced balanced turbo field echo sequence in abdominal imaging: a basic study.

    PubMed

    Nasu, Katsuhiro; Kuroki, Yoshifumi; Kuroki, Seiko; Murakami, Koji; Nawano, Shigeru; Moriyama, Noriyuki

    2004-07-15

    To determine the optimum imaging conditions for the balanced turbo field echo (bTFE) sequence in abdominal imaging, we performed phantom experiments and scanning of a normal volunteer while noting the correlation among signal intensity, k-space ordering, flow velocity and Gd-DTPA concentration. Initially, the abdomen of a healthy volunteer and some samples (water, blood and bovine albumin solutions with various Gd-DTPA concentrations, and olive oil) were examined with the bTFE sequence under various conditions to define the correlation among signal intensity, k-space ordering and Gd-DTPA concentration. Another experiment was performed to assess the correlation between the flow velocity and Gd-DTPA concentration. With the centric-bTFE sequence, we measured the signal intensity of water samples having various Gd-DTPA concentrations flowing in a long tube with an internal diameter of 4 mm. The experiments revealed the following issues: (i) The contrast of bTFE images was much influenced by k-space ordering; (ii) Gd-DTPA did not exhibit an overt enhancement effect in water and blood under stable conditions; (iii) The signal intensity of moving water decreased in centric-bTFE images, and this signal drop became more significant as the fluid speed increased; and (iv) Gd-DTPA decreased the range of signal loss in the moving fluid; however, this effect had no correlation with Gd-DTPA concentration. When the bTFE sequence was employed for abdominal imaging, centric view ordering, fat suppression and Gd-DTPA contrast enhancement were assumed to be necessary.

  8. Detection of pleural effusions and increased lung water by Tc-99m DTPA imaging

    SciTech Connect

    Glass, E.C.; Karelitz, J.R.; Bennett, L.R.

    1985-05-01

    The purpose of this study is to report a systematic observation of uptake or retention of Tc-99m DTPA in pleural effusions and other abnormal states of increased lung water. 24 patients who underwent renal imaging with 10 mCi Tc-99m DTPA were included. Imaging was performed with a large field of view camera for 0-03 minutes after injection and delayed images acquired 2-4 hours later. The images encompassed the mid and lower thorax as well as kidneys. 15 patients showed, at 0-5 minutes, cold areas at lung bases that later showed relatively increased activity at 2-4 hours (hot on delayed images). 14 of these 15 patients showed pleural effusions on chest x-ray. Small bilateral effusions were more clearly demonstrated by scan than by x-ray in 8 of 15 patients. One patient with pneumonia showed an immediate hot area in the infected lobe, and two with pulmonary edema and congestive failure showed diffuse lung retention of Tc-99m on delayed images. Among 9 patients who did not demonstrate abnormal cold or hot areas in their lungs on DTPA images, none had clinical or x-ray evidence of pleural effusion, pneumonia, or congestive failure (100% negative predictive value). Differences in rate constants for diffusion into vs. out of pleural fluid provide a plausible explanation for the observed retention of tracer in effusions, as seen on delayed images. This study indicates that imaging with Tc-99m DTPA provides information of diagnostic value in the detection of pleural effusions. Futhermore, the data suggests that DTPA imaging may also be useful as a simple, cost-effective method to detect other conditions in which regional lung water is abnormally increased.

  9. Multinuclear magnetic resonance study on the structure and dynamics of lanthanide(III) complexes of cyclic DTPA derivatives in aqueous solution

    SciTech Connect

    Bovens, E.; Hoefnagel, M.A.; Boers, E.

    1996-12-18

    The lanthanide coordination of the macrocyclic ligands cy(DTPA-EN) and cy (DTPA-EN-DTPA-EN) was studied in aqueous solution. {sup 17}O NMR measurements on the Dy{sup III} complexes showed that, in both complexes, the first coordination sphere of the Ln{sup III} ion contains one water molecule, leaving eight coordination sites for the ligand molecule. {sup 89}Y and {sup 139}La NMR analysis confirmed that the coordination mode of cy(DTPA-EN-DTPA-EN) is similar to that of the acyclic DTPA-bis(amide) derivatives. However, as a result of the cyclic nature of the similar to that of the acyclic DTPA-bis(amide) derivatives. However, as a result of the cyclic nature of the ligands considered the number of isomers in solution is lower than for the acyclic compounds. From variable-temperature {sup 1}H and {sup 13}C NMR data, the authors conclude that, in the respective Ln{sup III} complexes in solution, the cy(DTPA-EN) ligand is present in two rapidly interconverting isomers, whereas the cy(DTPA-EN-DTPA-EN) ligand exists in four isomeric forms. Two types of exchange processes are observed for the cy(DTPA-EN-DTPA-EN) complexes; one is fast on the NMR time scale and does not require decoordination of the ligand, and the second is relatively slow and decoordination is necessary to realize the interconversion. The complexes of cy(DTPA-EN) and the lighter Ln{sup III} ions (Ln = La {yields} Eu) precipitated, probably due to the formation of binuclear complexes. Comparisons are made with the previously studied acyclic DTPA-bis (amides).

  10. Explorations of TALSPEAK chemistry in extraction chromatography: Comparisons of TTHA with DTPA and HDEHP with HEH[EHP

    SciTech Connect

    Braley, Jenifer C.; McAlister, Daniel; Horwitz, E. P.; Nash, Kenneth L.

    2013-03-01

    An advanced nuclear fuel cycle includes a reprocessing stage for the group separation of the lanthanides from the trivalent actinides. The TALSPEAK (Trivalent Actinide - Lanthanide Separation by Phosphorus reagent Extraction from Aqueous Komplexes) solvent extraction process provides the An3+/Ln3+ separation through the use of an organic lanthanide extractant (bis-2-ethyl(hexyl) phosphoric acid, HDEHP) and an aqueous actinide-selective holdback reagent (diethylenetriamine-N,N,N’,N’’,N’’-pentaacetic acid, DTPA). Organic phase interactions in TALSPEAK have proven sufficiently complex that, even with substantial research effort, a descriptive thermodynamic model has yet to be developed. If one were to consider an extraction chromatographic (EXC) version of TALSPEAK, the presence of concentrated extractant on the resin surface should augment the multifaceted organic phase chemistry. This study examines the previously unexplored impact of each aqueous phase TALSPEAK component (holdback reagent, carboxylic acid buffer, and pH) on the chemistry of the EXC system. The presence of alternative reagents, 2-ethyl(hexyl) phosphonic acid mono-2-ethyl(hexyl) ester acid (HEH[EHP]) and triethylenetetramine-N,N,N’,N’’,N’’’,N’’’-hexaacetic acid (TTHA) are also considered. Results indicate the concentrated extractant appears to enhance solid-phase reactions that most likely involve water, lactate and sodium. The presumed water, lactate and sodium partitioning consumes resin capacity sufficiently that the weaker hold-back reagent under TALSPEAK aqueous conditions (pH ~ 3.6), TTHA, provides preferential Am3+/Ln3+ separations performance. If a TALSPEAK-EXC process were to be developed, a resin with solvent diluted extractant or covalently bound functional groups may be preferential to reduce the complexity of the solid-phase chemistry.

  11. An efficient optical-electrochemical dual probe for highly sensitive recognition of dopamine based on terbium complex functionalized reduced graphene oxide

    NASA Astrophysics Data System (ADS)

    Zhou, Zhan; Wang, Qianming

    2014-04-01

    A novel organic-inorganic hybrid sensor based on diethylenetriaminepentaacetic acid (DTPA) modified reduced graphene oxide (RGO-DTPA) chelated with terbium ions allows detection of dopamine (DA) through an emission enhancement effect. Its luminescence, peaking at 545 nm, has been improved by a factor of 25 in the presence of DA (detection limit = 80 nM). In addition, this covalently bonded terbium complex functionalized reduced graphene oxide (RGO-DTPA-Tb) can be successfully assembled on a glassy carbon electrode. The assay performed through differential pulse voltammetry (DPV) yielded obvious peak separation between DA and excessive amounts of the interfering ascorbic acid (AA).A novel organic-inorganic hybrid sensor based on diethylenetriaminepentaacetic acid (DTPA) modified reduced graphene oxide (RGO-DTPA) chelated with terbium ions allows detection of dopamine (DA) through an emission enhancement effect. Its luminescence, peaking at 545 nm, has been improved by a factor of 25 in the presence of DA (detection limit = 80 nM). In addition, this covalently bonded terbium complex functionalized reduced graphene oxide (RGO-DTPA-Tb) can be successfully assembled on a glassy carbon electrode. The assay performed through differential pulse voltammetry (DPV) yielded obvious peak separation between DA and excessive amounts of the interfering ascorbic acid (AA). Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr06156f

  12. Usage of radiopharmaceuticals in the development of pharmaceutical drug delivery systems: validation of [99mTc]DTPA and [99mTc]ECD.

    PubMed

    Terán, Mariella; Savio, Eduardo; Paolino, Andrea; Frier, Malcolm

    2004-03-01

    Tablets containing drugs of different lipophilicity, ranitidine and cinarizine, and placebo were prepared and their in vitro behaviour was studied by dissolution and disintegration tests. [(99m)Tc]Diethylenetriamine-pentaacetic acid ([(99m)Tc]DTPA) and [(99m)Tc]ethyl cysteinate dimer ([(99m)Tc]ECD) were used as tracers of the process. Both of them were added to tablets during wet granulation. Dissolution and disintegration profiles were assessed at different pH values (1, 4 and 7). Radioactivity was evaluated in filtered samples and scintigraphic studies were carried out in gamma camera. Stability in dissolution media was confirmed for both tracers under these conditions. Dissolution and disintegration velocity constants were calculated. [(99m)Tc]DTPA proved to be an appropriate tracer for polar drugs such as ranitidine. Nevertheless, it was not a suitable tracer for lipophilic active drugs such as cinarizine. On the other hand, the most lipophilic tracer, [(99m)Tc]ECD, exhibited the opposite behaviour. Scintigraphic studies of the disintegration process did not show significant differences between placebos and tablets containing active drugs. As disintegration is a physical process it does not discriminate between chemical differences in tablet formulations. Both methods complement each other because the dissolution process can be followed when a suitable radiotracer is chosen according to the physicochemical characteristics of the active drug.

  13. (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide exhibits higher tumor accumulation and lower renal radioactivity than (111)In-DTPA-d-Phe(1)-octreotide.

    PubMed

    Oshima, Nobuhiro; Akizawa, Hiromichi; Kitaura, Hirotake; Kawashima, Hidekazu; Zhao, Songji; Zhao, Yan; Nishijima, Ken-Ichi; Kitamura, Yoji; Arano, Yasushi; Kuge, Yuji; Ohkura, Kazue

    2017-07-12

    (111)In-DTPA-d-Phe(1)-octreotide scintigraphy is an important method of detecting neuroendocrine tumors. We previously reported that a new derivative of (111)In-DTPA-d-Phe(1)-octreotide, (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide, accomplished the reduction of prolonged renal accumulation of radioactivity. The aim of this study was to evaluate the tumor accumulation of (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide in vitro and in vivo by comparing it with (111)In-DTPA-d-Phe(1)-octreotide. The tumor accumulation of this octreotide derivative was determined by measuring its uptake using cultured AR42J cells in vitro and biodistribution studies in vivo. The distribution of the radiotracer and the extent of somatostatin receptor-specific uptake in the tumor were estimated by a counting method using AR42J tumor-bearing mice. The radioactive metabolite species in the tumor and kidney were identified by HPLC analyses at 3 and 24h post-injection of the (111)In-DTPA-conjugated peptide. In both cases, in vitro and in vivo, the tumor radioactivity levels of (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide were approximately 2-4 times higher than those of (111)In-DTPA-d-Phe(1)-octreotide. On in vitro cellular uptake inhibition and radioreceptor assay, (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide exhibited a binding affinity to somatostatin receptor highly similar to that of (111)In-DTPA-d-Phe(1)-octreotide. As the additional cellular uptake of (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide was significantly lower at low temperature than at 37°C, it was considered that a cellular uptake pathway is involved in energy-dependent endocytotic processes. In the radiometabolite analysis of (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide, (111)In-DTPA-d-Phe-Asp-OH was a major metabolite in the tumor at 24h post-injection. (111)In-DTPA-d-Phe(-1)-Asp(0)-d-Phe(1)-octreotide exhibited higher tumor accumulation and persistence of tumor radioactivity than (111)In-DTPA

  14. Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.

    PubMed

    Evans-Axelsson, Susan; Vilhelmsson Timmermand, Oskar; Welinder, Charlotte; Borrebaeck, Carl Ak; Strand, Sven-Erik; Tran, Thuy A; Jansson, Bo; Bjartell, Anders

    2014-01-01

    The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer.

  15. Preclinical evaluation of 111In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer

    PubMed Central

    Evans-Axelsson, Susan; Vilhelmsson Timmermand, Oskar; Welinder, Charlotte; Borrebaeck, Carl AK; Strand, Sven-Erik; Tran, Thuy A; Jansson, Bo; Bjartell, Anders

    2014-01-01

    The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the 111In-labeled human internalizing antibody, INCA-X (111In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of 111In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of 111In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the 111In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the 111In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer. PMID:24982817

  16. Magnetic nanoparticles modified with DTPA-AMC-rare earth for fluorescent and magnetic resonance dual mode imaging.

    PubMed

    Liu, Zengchen; Li, Bo; Wang, Baodui; Yang, Zhengyin; Wang, Qin; Li, Tianrong; Qin, Dongdong; Li, Yong; Wang, Mingfang; Yan, Mihui

    2012-07-28

    In the present study, we report new water-soluble cell fluorescence imaging and contrast agents that are based on DTPA-AMC(7-amino-4-methyl coumarin)-Eu(3+) and DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+) compounds conjugated to Fe(3)O(4) NPs via a PEG-NH(2) linker. The novel Fe(3)O(4) NP-conjugates present two main advantages for cell fluorescence labelling: water solubility and targeting ability. The in vitro experiments demonstrate that water-soluble Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Eu(3+) has excellent cell permeating activity. Moreover, the relaxation rate test of Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+) shows a higher T1 relaxation effect than traditional DTPA-Gd(3+) MRI agents. According to in vivo liver MRI experiments, better contrast of the liver was achieved after addition of Fe(3)O(4) NPs-DBI-PEG-NH-DTPA-AMC(7-amino-4-methyl coumarin)-Gd(3+). The results will provide a significant guide for researchers exploring the biomedical applications of superparamagnetic Fe(3)O(4) NPs.

  17. Influence of phosphorus sources and rates on soil pH, extractable phosphorus, and DTPA-extractable micronutrients

    SciTech Connect

    Al-Showk, A.M.; Westerman, R.L.; Weeks, D.L.

    1987-07-01

    Two soils (McLain sicl-fine, mixed, thermic, Pachic Argiustoll and Quinlan cl-loamy, mixed, thermic, shallow Typic Ustocrept) that differed in micronutrient content and chemical characteristics were collected from western Oklahoma. Soils were passed through a 2-mm screen and placed in plastic Petri dishes, and five P levels (0, 20, 40, 60, and 80 kg ha/sup -1/) were applied using monocalcium phosphate (MCP), monoammonium phosphate (MAP), and ammonium polyphosphate (APP); the soils were then mixed uniformly. Soils were moistened to approximately 0.33 MPa and incubated for 2 mo at room temperature. Application of P decreased soil pH in both soils, and MAP and APP had a greater effect than MCP, which was attributed to the nitrification of the added ammonium. Bray and Kurtz no. 1 P increased with P application in both soils. Monocalcium phosphate and MAP decreased DTPA-Fe, -Mn, and -Cu in McLain soil. However, high levels of P applied as APP increased DTPA-Fe, -Mn, and -Cu. Phosphorus application, regardless of source, had no effect on DTPA-Zn in McLain soil. Monocalcium phosphate and MAP decreased DTPA-Mn in the Quinlan soil; however; high levels of P applied as APP increased DTPA-Fe. Phosphorus application, regardless of source, had no effect on DTPA-Zn and -Cu in Quinlan soil.

  18. Evaluation of lung epithelial permeability in the volatile substance abuse using Tc-99m DTPA aerosol scintigraphy.

    PubMed

    Cayir, Derya; Demirel, Koray; Korkmaz, Meliha; Koca, Gokhan

    2011-10-01

    Chronic inhalant use is associated with significant toxic effects, including neurological, renal, hepatic, and pulmonary damage. However, there is a paucity of reports regarding respiratory complications in inhalant abusers. The aim of this study was to evaluate pulmonary epithelial permeability in the volatile substance abuse (VSA) using Tc-99m DTPA aerosol scintigraphy. This study included 18 patients with volatile substance abuse and 18 volunteer controls. All of patients and controls were smokers. Tc-99m DTPA aerosol scintigraphy was performed in all cases. Time-activity curves from each lung were generated and clearance half-time (T(1/2)) of Tc-99m DTPA were calculated. T(1/2) of whole lung was calculated as a mean of the T(1/2) of left and right lung. The T(1/2) values of Tc-99m DTPA clearance in the substance abusers were significantly decreased as compared to the control group with respective mean values of 28.86 ± 8.44, and 62.14 ± 26.12 min (p = 0.001). It was seen Tc-99m DTPA clearance from lung was faster as the duration of substance abuse was increased. Tc-99m DTPA pulmonary clearance is markedly accelerated in the volatile substance abuse. This suggests that inhalant abuse of substance may produce abnormalities in pulmonary alveolo-capillary membrane function.

  19. Gd DTPA: a review of clinical indications in central nervous system magnetic resonance imaging.

    PubMed

    Runge, V M; Carollo, B R; Wolf, C R; Nelson, K L; Gelblum, D Y

    1989-09-01

    Since its approval for clinical use in mid 1988, Gd DTPA has found widespread application as a contrast agent in MRI. This paramagnetic metal ion chelate is used primarily for enhancement of head and spine lesions. Indications for contrast agent use in MRI are summarized drawing upon experience in more than 600 patients and a review of the literature. Enhancement improves both lesion detection and categorization. In head examinations, we recommend use of Gd DTPA for studies of the internal auditory canal, metastatic disease, infarction, infection, meningeal disease, and primary neoplastic disease. In spine examinations, contrast enhancement is employed both for detection of neoplastic disease and in the postoperative back for the differentiation of scar from recurrent disk herniation. Gd DOTA and Gd DO3A-R are new agents within this same class of contrast media.

  20. Monopropionate analogues of DOTA4- and DTPA5-: kinetics of formation and dissociation of their lanthanide(III) complexes.

    PubMed

    Balogh, Edina; Tripier, Raphaël; Fousková, Petra; Reviriego, Felipe; Handel, Henri; Tóth, Eva

    2007-08-28

    The replacement of an acetate function of the macrocyclic DOTA4-(DO3A-Nprop4-) or the acyclic DTPA5- in terminal position (DTTA-Nprop5-) has been recently shown to result in a significant increase of the water exchange rate on the Gd3+ complexes, which makes these chelates potential contrast agents for MRI applications. Here, two novel and straightforward synthetic routes to H4DO3A-Nprop are described. Protonation constants of DO3A-Nprop4- and stability constants with several alkaline earth and transition metal ions have been determined by potentiometry. For each metal, the thermodynamic stability constant is decreased in comparison to the DOTA chelates. The formation reaction of LnDO3A-Nprop- complexes (Ln=Ce, Gd and Yb) proceeds via the rapid formation of a diprotonated intermediate and its subsequent deprotonation and rearrangement in a slow, OH- catalyzed process. The stability of the LnH2DO3A-Nprop* intermediates is similar to those reported for the corresponding DOTA analogues. The rate constants of the OH- catalyzed deprotonation step increase with decreasing lanthanide ion size, and are slightly higher than for DOTA complexes. The kinetic inertness of GdDTTA-Nprop2- was characterized by the rates of its exchange reactions with Zn2+ and Eu3+. The rate of the reaction between GdDTTA-Nprop2- and Zn2+ increases with Zn2+ concentration, while it is independent of pH, implying that the exchange takes place predominantly via direct attack of the metal ion on the complex. In the Eu3+ exchange, the rate decreases with increasing concentration of the exchanging ion which is accounted for by the transitional formation of a dinuclear GdDTTA-NpropEu+ species. The kinetic inertness of the monopropionate GdDTTA-Nprop2- is decreased in comparison to GdDTPA2-: all rate constants, characterizing the dissociation reaction via either proton- or metal-catalyzed pathways being higher by 1-2 orders of magnitude. Similarly, a study of the acid-catalyzed dissociation of the

  1. Characterization of Microcirculation in Multiple Sclerosis Lesions by Dynamic Texture Parameter Analysis (DTPA)

    PubMed Central

    Heldner, Mirjam Rahel; Kellner-Weldon, Frauke; Kottke, Raimund; Ozdoba, Christoph; Weisstanner, Christian; Kamm, Christian Philipp; Wiest, Roland

    2013-01-01

    Objective Texture analysis is an alternative method to quantitatively assess MR-images. In this study, we introduce dynamic texture parameter analysis (DTPA), a novel technique to investigate the temporal evolution of texture parameters using dynamic susceptibility contrast enhanced (DSCE) imaging. Here, we aim to introduce the method and its application on enhancing lesions (EL), non-enhancing lesions (NEL) and normal appearing white matter (NAWM) in multiple sclerosis (MS). Methods We investigated 18 patients with MS and clinical isolated syndrome (CIS), according to the 2010 McDonald's criteria using DSCE imaging at different field strengths (1.5 and 3 Tesla). Tissues of interest (TOIs) were defined within 27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based texture parameter maps (TPMs) were computed. TPMs quantify the heterogeneity of the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of-the-variance statistical parameters were calculated. These TOI parameters were further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank testing corrected for multiple comparisons. Results Tissue- and time-dependent differences were observed in the dynamics of computed texture parameters. Sixteen parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005). Significant differences in the DTPA texture maps were found during inflow (52 parameters), outflow (40 parameters) and reperfusion (62 parameters). The strongest discriminators among the TPMs were observed in the variance-related parameters, while skewness and kurtosis TPMs were in general less sensitive to detect differences between the tissues. Conclusion DTPA of DSCE image time series revealed characteristic time responses for ELs, NELs and NAWM. This may be further used for a refined quantitative grading of MS lesions during their evolution from acute to chronic state. DTPA discriminates lesions beyond features of enhancement or T2

  2. NMR and chiroptical examination of the diastereoisomers of (S)-Eu-EOB-DTPA.

    PubMed

    Thompson, Nicola C; Parker, David; Schmitt-Willich, Heribert; Sulzle, Detlev; Muller, Gilles; Riehl, James P

    2004-06-21

    The solution structure of the diastereoisomers of (S)-Eu--EOB--DTPA has been analysed by (1)H NMR, CD and CPL spectroscopy. Two major species exist which possess very similar (1)H NMR paramagnetic shifts and emission spectra, consistent with a 9-coordinate structure involving one bound water. Circularly polarised luminescence data are consistent with a common Lambda-helicity for each isomer; the isomers differ only in the absolute configuration of the central nitrogen atom.

  3. A case of bronchial carcinoid: diagnosis and follow-up with 111In-DTPA-octreotide.

    PubMed

    Orsolon, P; Bagni, B; Basadonna, P; Geatti, O; Talmassons, G; Guerra, U P

    1995-12-01

    Scintigraphy with radiolabelled analogue of somatostatin is highly sensitive in detecting carcinoid tumors especially if performed with Single Photon Computed Tomography (SPECT). In this report we describe our experience with 111In-DTPA-Octreotide in a female patient affected by a small asymptomatic intrabronchial carcinoid demonstrated by CT scan and bronchial endoscopy performed after recurrent left pneumonias. Planar views and SPECT images, using 111In-DTPA-Octreotide, were collected before and four hours after the first endoscopic laser resection. All groups of SPECT images were positive in the left parahilar region but at a different degree. Scans performed after resection showed a low degree of uptake which was considered to be probably secondary to local swelling; CT scan was negative. Follow up endoscopic biopsy repeated at six months, showed a relapse always in the same site; CT scan of the thorax was again negative. 111In-DTPA-Octreotide images obtained at twelve months were positive always in the left parahilar region, CT scan was negative but another biopsy was not possible. Therefore it was suspected a relapse of the carcinoid which was probably growing only through the bronchial wall without spreading towards the bronchial lumen and/or the lung parenchima. In this occasion, it was also thought that images collected four hours after resection could be positive not only for swelling but for a relapse as well. In every scintigraphic session, SPECT images presented higher quality than planar. This case suggests that 111In-DTPA-Octreotide SPECT is a non-invasive diagnostic technique which could be applied as a follow-up tool especially to patients with no-secreting carcinoid neoplasm and/or with negative or doubtful endoscopic and radiological investigations.

  4. Characterization of microcirculation in multiple sclerosis lesions by dynamic texture parameter analysis (DTPA).

    PubMed

    Verma, Rajeev Kumar; Slotboom, Johannes; Heldner, Mirjam Rachel; Heldner, Mirjam Rahel; Kellner-Weldon, Frauke; Kottke, Raimund; Ozdoba, Christoph; Weisstanner, Christian; Kamm, Christian Philipp; Wiest, Roland

    2013-01-01

    Texture analysis is an alternative method to quantitatively assess MR-images. In this study, we introduce dynamic texture parameter analysis (DTPA), a novel technique to investigate the temporal evolution of texture parameters using dynamic susceptibility contrast enhanced (DSCE) imaging. Here, we aim to introduce the method and its application on enhancing lesions (EL), non-enhancing lesions (NEL) and normal appearing white matter (NAWM) in multiple sclerosis (MS). We investigated 18 patients with MS and clinical isolated syndrome (CIS), according to the 2010 McDonald's criteria using DSCE imaging at different field strengths (1.5 and 3 Tesla). Tissues of interest (TOIs) were defined within 27 EL, 29 NEL and 37 NAWM areas after normalization and eight histogram-based texture parameter maps (TPMs) were computed. TPMs quantify the heterogeneity of the TOI. For every TOI, the average, variance, skewness, kurtosis and variance-of-the-variance statistical parameters were calculated. These TOI parameters were further analyzed using one-way ANOVA followed by multiple Wilcoxon sum rank testing corrected for multiple comparisons. Tissue- and time-dependent differences were observed in the dynamics of computed texture parameters. Sixteen parameters discriminated between EL, NEL and NAWM (pAVG = 0.0005). Significant differences in the DTPA texture maps were found during inflow (52 parameters), outflow (40 parameters) and reperfusion (62 parameters). The strongest discriminators among the TPMs were observed in the variance-related parameters, while skewness and kurtosis TPMs were in general less sensitive to detect differences between the tissues. DTPA of DSCE image time series revealed characteristic time responses for ELs, NELs and NAWM. This may be further used for a refined quantitative grading of MS lesions during their evolution from acute to chronic state. DTPA discriminates lesions beyond features of enhancement or T2-hypersignal, on a numeric scale allowing for a

  5. [177Lu]Bz-DTPA-EGF: Preclinical characterization of a potential radionuclide targeting agent against glioma.

    PubMed

    Sundberg, Asa Liljegren; Gedda, Lars; Orlova, Anna; Bruskin, Alexander; Blomquist, Erik; Carlsson, Jörgen; Tolmachev, Vladimir

    2004-04-01

    Patients with glioblastoma multiforme have a poor prognosis due to recurrences originating from spread cells. The use of radionuclide targeting might increase the chance of inactivating single tumor cells with minimal damage to surrounding healthy tissue. As a target, overexpressed epidermal growth factor receptors (EGFR) may be used. A natural ligand to EGFR, the epidermal growth factor (EGF) is an attractive targeting agent due to its low molecular weight (6 kDa) and high affinity for EGFR. 177Lu (T(1/2) = 6.7 days) is a radionuclide well suited for treatment of small tumor cell clusters, since it emits relatively low-energy beta particles. The goal of this study was to prepare and preclinically evaluate both in vitro and in vivo the [177Lu]Bz-DTPA-EGF conjugate. The conjugate was characterized in vitro for its cell-binding properties, and in vivo for its pharmacokinetics and ability to target EGFR. [177Lu]Bz-DTPA-EGF bound to cultured U343 glioblastoma cells with an affinity of 1.9 nM. Interaction with EGFR led to rapid internalization, and more than 70% of the cell-associated radioactivity was internalized after 30 minutes of incubation. The retention of radioactivity was good, with more than 65% of the 177Lu still cell-associated after 2 days. Biodistribution studies of i.v. injected [177Lu]Bz-DTPA-EGF in NMRI mice demonstrated a rapid blood clearance. Most of the radioactivity was found in the liver and kidneys. The liver uptake was receptor-mediated, since it could be significantly reduced by preinjection of unlabeled EGF. In conclusion, [177Lu]Bz-DTPA-EGF seems to be a promising candidate for locoregional treatment of glioblastoma due to its high binding affinity, low molecular weight, and ability to target EGFR in vivo.

  6. The behavior and importance of lactic acid complexation in Talspeak extraction systems

    SciTech Connect

    Grimes, Travis S.; Nilsson, Mikael; Nash, Kenneth L.

    2008-07-01

    Advanced partitioning of spent nuclear fuel in the UREX +la process relies on the TALSPEAK process for separation of fission-product lanthanides from trivalent actinides. The classic TALSPEAK utilizes an aqueous medium of both lactic acid and diethylenetriaminepentaacetic acid and the extraction reagent di(2-ethylhexyl)phosphoric acid in an aromatic diluent. In this study, the specific role of lactic acid and the complexes involved in the extraction of the trivalent actinides and lanthanides have been investigated using {sup 14}C-labeled lactic acid. Our results show that lactic acid partitions between the phases in a complex fashion. (authors)

  7. Rapid clearance of inhaled aerosols of Technetium-99M DTPA in patients with pneumocystis carinii pneumonia

    SciTech Connect

    Mason, G.R.; Duane, G.B.; Effros, R.M.; Mena, I.

    1985-05-01

    Because infection with Pheumocystis carinii pneumonia (PCP) causes alteration of the type I epithelial cells as the primary event, the authors studied patients with PCP to determine if PCP causes rapid clearance of Tc-99m DTPA. Twenty normal non-smoking subjects and 7 non-smoking patients with histologically proven PCP were studied. Serial studies were obtained in three patients. Following a two-minute inhalation of 1.6 ..mu..m aerosol particles of Tc-99m DTPA in saline, the activity over three peripheral regions of interest (ROI) of each lung was monitored for the next 7 minutes. The rate of decline of activity over each ROI was expressed as per cent decline/min. In 7 patients with PCP, the average clearance was 7.5 +- 3.6% min., normal, 1.3 +- 0.6% min.(SD). Three patients studied from 5 to 38 days following therapy had improvement in the rate of clearance. This has been demonstrated to be persistent even after clinical recovery of the patient. The ability to quantitate injury to the pulmonary epithelium may directly reflect the ability of Pneumocystis carinii to invade the lung. The authors conclude that Tc-99m DTPA clearance may be a useful test to help diagnosis and monitor the activity of PCP infections.

  8. Clearance of Tc-99m DTPA aerosol from coal miners' lungs

    SciTech Connect

    Susskind, H.; Brill, A.B.; Harold, W.H.

    1985-07-01

    Alterations in regional epithelial permeability were assessed in 22 retired West Virginia coal miners' lungs by measuring the clearance of inhaled 0.5-..mu..m Tc-99m DTPA aerosol. Activity was measured in both lungs and in regions of interest placed over the lung periphery in the apical, middle, and basal portions of each lung. Clearance rates (T/sub 1/2/) for 5 nonsmokers, 8 ex-smokers, and 9 smokers were significantly faster than for comparable subjects measured elsewhere, who were not coal miners. Regional apex-to-base distributions of DTPA were measured as a function of clearance time and compared with regional ventilation and perfusion. Regional, as well as overall lung clearance curves of 8 smokers and 4 ex-smokers had two components, with overall T/sub 1/2/ of <7 min for the faster one. No correlations were found between T/sub 1/2/ and DLCO or with P(A-a)O/sub 2/. The results of our study suggest that measurement of DTPA clearance is a potentially useful noninvasive technique to assess lung injury in miners exposed to coal dust. 14 refs., 6 figs., 2 tabs.

  9. Evaluation of technetium-99m DTPA for localization of site of acute upper gastrointestinal bleeding

    SciTech Connect

    Abdel-Dayem, H.M.; Mahajan, K.K.; Ericsson, S.; Nawaz, K.; Owunwanne, A.; Kouris, K.; Higazy, E.; Awdeh, M.

    1986-11-01

    Intravenous Tc-99m DTPA was evaluated in 34 patients with active upper gastrointestinal bleeding. Active bleeding was detected in 25 patients: nine in the stomach, 12 in the duodenum, and four from esophageal varices. No active bleeding was seen in nine patients (two gastric ulcers and seven duodenal ulcers). Results were correlated with endoscopic and/or surgical findings. All completely correlated except: 1) one case of esophageal varices in which there was disagreement on the site, 2) three cases of duodenal ulcers that were not bleeding on endoscopy but showed mild oozing on delayed images and 3) one case of gastric ulcer, in which no bleeding was detected in the Tc-99m DTPA study, but was found to be bleeding at surgery 24 hours later. The Tc-99m DTPA study is a reliable method for localization of upper gastrointestinal bleeding with an agreement ratio of 85%. This method also can be used safely for follow-up of patients with intermittent bleeding. It is less invasive than endoscopy, is easily repeatable, and has the same accuracy.

  10. Evaluation of the viability of /sup 111/In-abeled DTPA coupled to fibrinogen

    SciTech Connect

    Layne, W.W.; Hnatowich, D.J.; Doherty, P.W.; Childs, R.L.; Lanteigne, D.; Ansell, J.

    1982-07-01

    In earlier work, DTPA has been covalently coupled to albumin via the cyclic anhydride of DTPA. Using fibrinogen, we have studied the effect of such coupling on protein viability by both an in vitro and an in vivo assay. Clotting time remained identical to that of the native protein whether the anhydride-to-protein molar ratio was 1:1 or 5:1. In vivo studies were done in dogs, with human fibrinogen labeled with /sup 125/I and /sup 111/In. Throughout 130 hr, blood clearances for the two tracers agreed whether with 1:1 or 5:1 coupling. In a dog model with a thrombogenic catheter, the clot-to-blood ratios for the two radiotracers agreed within experimental error. Finally, 1:1-coupled canine fibrinogen, labeled with /sup 111/In, was administered to dogs with a catheter in a jugular vein, and scintigrams at 24 hr clearly showed clotting along the length of the catheter. We conclude that fibrinogen, coupled to DTPA, retains its viability, behaving like radioiodinated fibrinogen in vivo, and /sup 111/In labeled fibrinogen looks promising as a clinical diagnostic agent.

  11. Gd-EOB-DTPA-enhanced MR relaxometry for the detection and staging of liver fibrosis

    PubMed Central

    Haimerl, Michael; Utpatel, Kirsten; Verloh, Niklas; Zeman, Florian; Fellner, Claudia; Nickel, Dominik; Teufel, Andreas; Fichtner-Feigl, Stefan; Evert, Matthias; Stroszczynski, Christian; Wiggermann, Philipp

    2017-01-01

    Gd-EOB-DTPA, a liver-specific contrast agent with T1-shortening effects, is routinely used in clinical routine for detection and characterization of focal liver lesions and has recently received increasing attention as a tool for the quantitative analyses of liver function. We report the relationship between the extent of Gd-EOB-DTPA- induced T1 relaxation and the degree of liver fibrosis, which was assessed according to the METAVIR score. For the T1 relaxometry, a transverse 3D VIBE sequence with inline T1 calculation was acquired prior to and 20 minutes after Gd-EOB-DTPA administration. The reduction rates of the T1 relaxation time (rrT1) between the pre- and postcontrast images were calculated, and the optimal cutoff values for the fibrosis stages were determined with receiver operating characteristic (ROC) curve analyses. The rrT1 decreased with the severity of liver fibrosis and regression analysis revealed a significant correlation of the rrT1 with the stage of liver fibrosis (r = −0.906, p < 0.001). ROC analysis revealed sensitivities ≥78% and specificities ≥94% for the differentiation of different fibrosis stages. Gd-EOB-DTPA–enhanced T1 relaxometry is a reliable tool for both the detection of initial hepatic fibrosis and the staging of hepatic fibrosis. PMID:28128291

  12. In vitro and in vivo assessment of plutonium speciation and decorporation in blood and target retention tissues after a systemic contamination followed by an early treatment with DTPA.

    PubMed

    Sérandour, A L; Grémy, O; Fréchou, M; Renault, D; Poncy, J L; Fritsch, P

    2008-08-01

    This study identifies the main sources of systemic plutonium decorporated in the rat after DTPA i.v. at the dose recommended for humans (30 mumol kg(-1)). For this purpose, standard biokinetic approaches are combined to plasma ultrafiltration for separation of plutonium complexes according to their molecular weight. In vitro studies show that at the recommended DTPA dose, less than 5% of the plasma plutonium of contaminated rats can be displaced from high-molecular-weight ligands. After i.v. administration of Pu-DTPA, early ultrafiltrability of plutonium in plasma decreases with total DTPA dose, which is associated with an increase in plutonium bone retention. This demonstrates the instability of Pu-DTPA complexes, injected in vivo, below the minimal Ca-DTPA dose of 30 mumol kg(-1). Plutonium biokinetics is compared in rats contaminated by plutonium-citrate i.v. and treated or not with DTPA after 1 h. No significant decrease in plasma plutonium is observed for the first hour after treatment, and the fraction of low-molecular-weight plutonium in plasma is nearly constant [5.4% compared with 90% in Pu-DTPA i.v. (30 mumol kg(-1)) and 0.7% in controls]. Thus plutonium decorporation by DTPA is a slow process that mainly involves retention compartments other than the blood. Plutonium-ligand complexes formed during plutonium deposition in the retention organs appear to be the main source of decorporated plutonium.

  13. A simple and inexpensive system for controlling body temperature in small animal experiments using MRI and the effect of body temperature on the hepatic kinetics of Gd-EOB-DTPA.

    PubMed

    Murase, Kenya; Assanai, Purapan; Takata, Hiroshige; Saito, Shigeyoshi; Nishiura, Motoko

    2013-12-01

    The purpose of this study was to develop a simple and inexpensive system for controlling body temperature in small animal experiments using magnetic resonance imaging (MRI) and to investigate the effect of body temperature on the kinetic behavior of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in the liver. In our temperature-control system, body temperature was controlled using a feedback-regulated heated or cooled air flow generated by two Futon dryers. The switches of the two Futon dryers were controlled using a digital temperature controller, in which the rectal temperature of a mouse measured by an optical fiber thermometer was used as the input. In experimental studies, male ICR mice aged 8weeks old were used and allocated into 5 groups (39-, 36-, 33-, 30-, and 27-degree groups, n=10), in which the body temperature was maintained at 39 °C, 36 °C, 33 °C, 30 °C, and 27 °C, respectively, using our system. The dynamic contrast-enhanced MRI (DCE-MRI) data were acquired with an MRI system for animal experiments equipped with a 1.5-Tesla permanent magnet, for approximately 43min, after the injection of Gd-EOB-DTPA into the tail vein. After correction of the image shift due to the temperature-dependent drift of the Larmor frequency using the gradient-based image registration method with robust estimation of displacement parameters, the kinetic behavior of Gd-EOB-DTPA was analyzed using an empirical mathematical model. With the use of this approach, the upper limit of the relative enhancement (A), the rates of contrast uptake (α) and washout (β), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum relative enhancement (REmax), the time to REmax (Tmax), and the elimination half-life of the contrast agent (T1/2) were calculated. The body temperature of mice could be controlled well by use of our system. Although there were no significant differences in α, AUC, and q among groups, there

  14. A comparative evaluation of the chelators H4octapa and CHX-A″-DTPA with the therapeutic radiometal 90Y☆

    PubMed Central

    Price, Eric W.; Edwards, Kimberly J.; Carnazza, Kathryn E.; Carlin, Sean D.; Zeglis, Brian M.; Adam, Michael J.; Orvig, Chris; Lewis, Jason S.

    2016-01-01

    Objectives To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal 90Y. 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 90Y 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 90Y-CHX-A′-DTPA-trastuzumab and 90Y-octapa-trastuzumab after 15 min at room temperature. Both 90Y-CHX-A″-DTPA-trastuzumab and 90Y-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 90Y-CHX-A″-DTPA-trastuzumab and 30.1 ± 7.4%ID/g for 90Y-octapa-trastuzumab at 72 h post-injection) in mice bearing HER2-expressing SKOV3 ovarian cancer xenografts. Finally, 90Y radioimmunotherapy studies performed in tumor-bearing mice demonstrated that 90Y-CHX-A″-DTPA-trastuzumab and 90Y-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 90Y. PMID:27419360

  15. A comparative evaluation of the chelators H4octapa and CHX-A″-DTPA with the therapeutic radiometal (90)Y.

    PubMed

    Price, Eric W; Edwards, Kimberly J; Carnazza, Kathryn E; Carlin, Sean D; Zeglis, Brian M; Adam, Michael J; Orvig, Chris; Lewis, Jason S

    2016-09-01

    To compare the radiolabeling performance, stability, and practical efficacy of the chelators CHX-A″-DTPA and H4octapa with the therapeutic radiometal (90)Y. 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. 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. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Model-based comparison of maternal and foetal organ doses from (99m)Tc pertechnetate, DMSA, DTPA, HDP, MAA and MAG(3) diagnostic intakes during pregnancy.

    PubMed

    Saunders, Margaret; Palmer, Maria; Preece, Alan; Millard, Roger

    2002-10-01

    Organ residence times were calculated for diagnostic intakes of (99m)Tc pertechnetate, 2,3-dimercaptosuccinic acid (DMSA), diethylene triamine penta-acetic acid (DTPA), hydroxymethylene diphosphonate (HDP), macroaggregated albumin (MAA) and mercapto-acetyltriglycine (MAG(3)) during the 1st and 3rd stages of pregnancy and used with the MIRDOSE3 pregnant female phantoms for generation of dose estimates. At stage 3 individual foetal organ doses were estimated via a surrogate phantom based on that for the new-born but with mean dose/cumulated activity ( S) values scaled for compatibility with foetal whole body S. Stage 1 or 3 whole foetus doses ranged from 5.2 to 0.77 microGy MBq(-1) respectively, analogous to current ICRP estimates for these agents using similar in vivo biodistribution model databases. Most stage 3 maternal and foetal organ doses were similar within a factor of 3, being higher in the foetus than the mother with pertechnetate, DTPA and MAG(3), and lower with DMSA, HDP and MAA. Doses were more uniformly distributed among foetal organs than in the mother. Placental transfer was greatest with pertechnetate, where dose to the stage 3 foetal thyroid was 60-140 microGy MBq(-1). With each agent there was more placental transfer in stage 3 than in stage 1, but doses to stage 1 whole foetus were always higher, with the contribution from the mother dominant. For DMSA, HDP and MAG(3) the maternal contribution to total foetal body dose exceeded 93% for both stages.

  17. Synthesis of specific SPECT-radiopharmaceutical for tumor imaging based on methionine: 99mTc-DTPA-bis(methionine).

    PubMed

    Hazari, Puja Panwar; Shukla, Gauri; Goel, Vijay; Chuttani, Krishna; Kumar, Nitin; Sharma, Rajnish; Mishra, Anil Kumar

    2010-02-17

    Methionine-diethylenetriaminepentaaceticacid-methionine [DTPA-bis(Met)] was synthesized by covalently conjugating two molecules of methionine (Met) to DTPA and was labeled with (99m)Tc in high radiochemical purity and specific activity (166-296 MBq/micromol). Kinetic analysis showed K(m) of 12.95 +/- 3.8 nM and a maximal transport rate velocity (V(max)) of 80.35 +/- 0.42 pmol microg protein(-1) min(-1) of (99m)Tc-DTPA-bis(Met) in U-87MG cells. DTPA-bis(Met) had dissociation constants (K(d)) of 0.067 and 0.077 nM in U-87MG and BMG, respectively. (35)S-methionine efflux was trans-stimulated by (99m)Tc-labeled DTPA conjugate demonstrating concentrative transport. The blood kinetic studies showed fast clearance with t(1/2) (F) = 36 +/- 0.5 min and t(1/2) (S) = 5 h 55 min +/- 0.85 min. U-87MG and BMG tumors saturated at approximately 2000 +/- 280 nmol/kg of (99m)Tc-DTPA-bis(Met). Initial rate of transport of (99m)Tc-DTPA-bis(Met) in U-87MG tumor was found to be 4.68 x 10(-4) micromol/kg/min. The tumor (BMG cell line, malignant glioma) grafted in athymic mice were readily identifiable in the gamma images. Semiquantitative analysis from region of interest (ROI) placed over areas counting average counts per pixel with maximum radiotracer uptake on the tumor was found to be 11.05 +/- 3.99 and compared ROI with muscle (0.55 +/- 0.13). The tumor-to-contralateral muscle tissue ratio of (99m)Tc-DTPA-bis(Met) was found to be 23 +/- 3.3. Biodistribution revealed significant tumor uptake and good contrast in the U-87MG, BMG, and EAT tumor-bearing mice. In clinical trials, the sensitivity, specificity, and positive predictive values were found to be 87.8%, 92.8%, and 96.6%, respectively. (99m)Tc-DTPA-bis(Met) showed excellent tumor targeting and has promising utility as a SPECT-radiopharmaceutical for imaging methionine-dependent human tumors and to quantify the ratio of MET(+)/HCY(-).

  18. PET imaging of HER1-expressing xenografts in mice with 86Y-CHX-A''-DTPA-cetuximab.

    PubMed

    Nayak, Tapan K; Regino, Celeste A S; Wong, Karen J; Milenic, Diane E; Garmestani, Kayhan; Baidoo, Kwamena E; Szajek, Lawrence P; Brechbiel, Martin W

    2010-07-01

    Cetuximab is a recombinant, human/mouse chimeric IgG(1) monoclonal antibody that binds to the epidermal growth factor receptor (EGFR/HER1). Cetuximab is approved for the treatment of patients with HER1-expressing metastatic colorectal cancer. Limitations in currently reported radiolabeled cetuximab for PET applications prompted the development of (86)Y-CHX-A''-DTPA-cetuximab as an alternative for imaging HER1-expressing cancer. (86)Y-CHX-A''-DTPA-cetuximab can also serve as a surrogate marker for (90)Y therapy. Bifunctional chelate, CHX-A''-DTPA was conjugated to cetuximab and radiolabeled with (86)Y. In vitro immunoreactivity was assessed in HER1-expressing A431 cells. In vivo biodistribution, PET imaging and noncompartmental pharmacokinetics were performed in mice bearing HER1-expressing human colorectal (LS-174T and HT29), prostate (PC-3 and DU145), ovarian (SKOV3) and pancreatic (SHAW) tumor xenografts. Receptor blockage was demonstrated by coinjection of either 0.1 or 0.2 mg cetuximab. (86)Y-CHX-A''-DTPA-cetuximab was routinely prepared with a specific activity of 1.5-2 GBq/mg and in vitro cell-binding in the range 65-75%. Biodistribution and PET imaging studies demonstrated high HER1-specific tumor uptake of the radiotracer and clearance from nonspecific organs. In LS-174T tumor-bearing mice injected with (86)Y-CHX-A''-DTPA-cetuximab alone, (86)Y-CHX-A''-DTPA-cetuximab plus 0.1 mg cetuximab or 0.2 mg cetuximab, the tumor uptake values at 3 days were 29.3 +/- 4.2, 10.4 +/- 0.5 and 6.4 +/- 0.3%ID/g, respectively, demonstrating dose-dependent blockage of the target. Tumors were clearly visualized 1 day after injecting 3.8-4.0 MBq (86)Y-CHX-A''-DTPA-cetuximab. Quantitative PET revealed the highest tumor uptake in LS-174T (29.55 +/- 2.67%ID/cm(3)) and the lowest tumor uptake in PC-3 (15.92 +/- 1.55%ID/cm(3)) xenografts at 3 days after injection. Tumor uptake values quantified by PET were closely correlated (r (2) = 0.9, n = 18) with values determined by

  19. The role of equilibrium and kinetic properties in the dissociation of Gd[DTPA-bis(methylamide)] (Omniscan) at near to physiological conditions.

    PubMed

    Baranyai, Zsolt; Brücher, Ernő; Uggeri, Fulvio; Maiocchi, Alessandro; Tóth, Imre; Andrási, Melinda; Gáspár, Attila; Zékány, László; Aime, Silvio

    2015-03-16

    [Gd(DTPA-BMA)] is the principal constituent of Omniscan, a magnetic resonance imaging (MRI) contrast agent. In body fluids, endogenous ions (Zn(2+), Cu(2+), and Ca(2+)) may displace the Gd(3+). To assess the extent of displacement at equilibrium, the stability constants of DTPA-BMA(3-) complexes of Gd(3+), Ca(2+), Zn(2+), and Cu(2+) have been determined at 37 °C in 0.15 M NaCl. The order of these stability constants is as follows: GdL≈CuL>ZnL≫CaL. Applying a simplified blood plasma model, the extent of dissociation of Omniscan (0.35 mM [Gd(DTPA-BMA)]) was found to be 17% by the formation of Gd(PO4), [Zn(DTPA-BMA)](-) (2.4%), [Cu(DTPA-BMA)](-) (0.2%), and [Ca(DTPA-BMA)](-) (17.7%). By capillary electrophoresis, the formation of [Ca(DTPA-BMA)](-) has been detected in human serum spiked with [Gd(DTPA-BMA)] (2.0 mM) at pH 7.4. Transmetallation reactions between [Gd(DTPA-BMA)] and Cu(2+) at 37 °C in the presence of citrate, phosphate, and bicarbonate ions occur by dissociation of the complex assisted by the endogenous ligands. At physiological concentrations of citrate, phosphate, and bicarbonate ions, the half-life of dissociation of [Gd(DTPA-BMA)] was calculated to be 9.3 h at pH 7.4. Considering the rates of distribution and dissociation of [Gd(DTPA-BMA)] in the extracellular space of the body, an open two-compartment model has been developed, which allows prediction of the extent of dissociation of the Gd(III) complex in body fluids depending on the rate of elimination of the contrast agent. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Detection of diffuse glomerular lesions in rats: II. Comparison of indium-111 cationic small macromolecules with technetium-99m DTPA

    SciTech Connect

    McAfee, J.G.; Thomas, F.D.; Subramanian, G.; Schneider, R.D.; Lyons, B.; Roskopf, M.; Zapf-Longo, C.; Whaley, D.

    1986-04-01

    Dextrans with average molecular weights of 5000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls. However, there was poor correlation between the early renal uptake of these agents and the clearance of simultaneously injected (/sup 99m/Tc)DTPA. The 2-hr organ distribution and urinary excretion of these agents were compared with the corresponding values of DTPA. The differences in clearance between rats with glomerular damage and controls were greater with aminated dextran (mol wt 5000) than with DTPA, confirming previous work with infusions of nonradioactive charged dextrans and neutral inulin. The cationic dextrans appear to reflect the presence or absence of the normal anionic charge of the glomerular membrane as well as changes in filtration rate. Aminated inulin did not differentiate between controls and rats with glomerular disease any better than DTPA, probably because the number of amino groups conjugated was insufficient to produce the charge effect.

  1. Comparison of Tl-201 renal uptake with Tc-99m DTPA angiorenography in patients with hypertension. Measures of renal asymmetry.

    PubMed

    Hurwitz, G A; Powe, J E; Wesolowski, C A; Mattar, A G

    1992-06-01

    Renal uptake of Tl-201 reflects renal perfusion and may have a role in defining renal asymmetry in patients with hypertension who are referred for myocardial scintigraphy. The authors compared two methods of quantitating differential renal uptake of Tl-201, with similar data obtained from the angiographic and renal uptake (RU) phases of Tc-99m DTPA scintigraphy in 35 patients with hypertension. For Tl-201, asymmetry in renal counts was quantitated based on a simple outline technique or on interpolative background subtraction of 5-minute posterior images. Inter-observer and intra-observer variability among duplicate measurements were lower for Tl-201, particularly with interpolative background subtraction, than for Tc-99m DTPA. Renal/background ratios were similar for Tl-201 and RU-phase Tc-99m DTPA images when considering liver, spleen, or inter-renal regions as background; however, paraspinal uptake was relatively higher with Tl-201 (P less than 0.01). Qualitatively, renal asymmetry scores with the two radiotracers agreed (r = 0.89, blinded readings by four observers), although asymmetry was more marked with Tl-201 (P = 0.06). Measurements with Tl-201 agreed with both phases of Tc-99m DTPA (r = 0.96 to 0.98), but interpolative background subtraction systematically yielded greater inter-renal asymmetry than RU (P less than 0.01), reflecting the qualitative impression. Thus, ancillary Tl-201 imaging reflects differences between the kidneys in a fashion similar but not identical to Tc-99m DTPA scintigraphy.

  2. Effects of the Magnetic Resonance Imaging Contrast Agent Gd-DTPA on Plant Growth and Root Imaging in Rice

    PubMed Central

    Liu, Binmei; Wang, Qi; Ni, Xiaoyu; Dong, Yaling; Zhong, Kai; Wu, Yuejin

    2014-01-01

    Although paramagnetic contrast agents have a wide range of applications in medical studies involving magnetic resonance imaging (MRI), these agents are seldom used to enhance MRI images of plant root systems. To extend the application of MRI contrast agents to plant research and to develop related techniques to study root systems, we examined the applicability of the MRI contrast agent Gd-DTPA to the imaging of rice roots. Specifically, we examined the biological effects of various concentrations of Gd-DTPA on rice growth and MRI images. Analysis of electrical conductivity and plant height demonstrated that 5 mmol Gd-DTPA had little impact on rice in the short-term. The results of signal intensity and spin-lattice relaxation time (T1) analysis suggested that 5 mmol Gd-DTPA was the appropriate concentration for enhancing MRI signals. In addition, examination of the long-term effects of Gd-DTPA on plant height showed that levels of this compound up to 5 mmol had little impact on rice growth and (to some extent) increased the biomass of rice. PMID:24945975

  3. Effects of the magnetic resonance imaging contrast agent Gd-DTPA on plant growth and root imaging in rice.

    PubMed

    Liu, Zan; Qian, Junchao; Liu, Binmei; Wang, Qi; Ni, Xiaoyu; Dong, Yaling; Zhong, Kai; Wu, Yuejin

    2014-01-01

    Although paramagnetic contrast agents have a wide range of applications in medical studies involving magnetic resonance imaging (MRI), these agents are seldom used to enhance MRI images of plant root systems. To extend the application of MRI contrast agents to plant research and to develop related techniques to study root systems, we examined the applicability of the MRI contrast agent Gd-DTPA to the imaging of rice roots. Specifically, we examined the biological effects of various concentrations of Gd-DTPA on rice growth and MRI images. Analysis of electrical conductivity and plant height demonstrated that 5 mmol Gd-DTPA had little impact on rice in the short-term. The results of signal intensity and spin-lattice relaxation time (T1) analysis suggested that 5 mmol Gd-DTPA was the appropriate concentration for enhancing MRI signals. In addition, examination of the long-term effects of Gd-DTPA on plant height showed that levels of this compound up to 5 mmol had little impact on rice growth and (to some extent) increased the biomass of rice.

  4. Influence of methionine administration during chelation of cadmium by CaNa(3)DTPA and DMPS in the rat.

    PubMed

    Tandon, S K; Singh, S; Prasad, S

    1997-07-01

    Influence of methionine administration was investigated in rats on the efficacy of calcium trisodium diethylenetriamine pentaacetate (CaNa(3)DTPA) and 2,3-dimercaptopropane-1 sulfonate (DMPS) in the treatment of cadmium intoxication. CaNa(3)DTPA, DMPS or methionine were quite effective in mobilizing cadmium from blood and all the tissues examined in cadmium pre-exposed animals. The combination of CaNa(3)DTPA and methionine was more efficient in reducing hepatic, renal and heart cadmium levels while that of DMPS and methionine was more efficient in lowering liver, kidney and brain cadmium levels than either of them alone. The combinations were also highly effective in enhancing the urinary and the fecal excretion of cadmium. The treatment with CaNa(3)DTPA, DMPS or methionine was quite effective in reversing cadmium inhibited tissue enzymes and alterations in blood and serum biochemical levels. The combined treatment with a chelator and methionine was more effective than the chelators alone in restoring cadmium induced changes in hepatic and renal transaminases. The treatment with CaNa(3)DTPA, DMPS or methionine appreciably decreased the depletion of endogenous zinc, copper and iron due to cadmium but the combined treatments were more efficient than the individuals in restoring the kidney and the brain copper levels only. The results show that the administration of methionine during chelation therapy may be beneficial in the treatment of cadmium intoxication.

  5. Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging

    PubMed Central

    Gaffney, K.; Cookson, J.; Blades, S.; Coumbe, A.; Blake, D.

    1998-01-01

    OBJECTIVE—To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI).
METHODS—Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area).
RESULTS—Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement.
CONCLUSIONS—Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

 Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity PMID:9640130

  6. Radionuclide studies of chronic schistosomal uropathy. [/sup 99m/Tc-DTPA; /sup 131/I-hippuran

    SciTech Connect

    Lamki, L.M.; Lamki, N.

    1981-08-01

    Fifty patients with chronic urinary tract schistosomiasis were studied with /sup 99m/Tc-DTPA. All had a flow study, sequential analog imaging, and digital imaging for 25 to 35 min (20-sec frames). Time-activity curves (DTPA renograms) were extracted; 12 patients had /sup 131/I-Hippuran probe renograms as well. Renal changes included diminished perfusion and structural abnormalities ranging from minor calyceal dilatation to overt hydronephrosis. Ureteral changes included dilatation, tortuosity, and kinking. Marked distortion of the ureterovesical junction was seen in some patients due to periureteral and perivesicular fibrosis, which is a major factor in upper urinary tract damage. Renograms showed varying obstruction and parenchymal damage. Nuclear medicine complements excretory urography and is sometimes preferable for visualization of the ureters. After the initial urogram, sequential DTPA scanning and renography are sufficient for follow-up.

  7. Hybrid core shell nanoparticles entrapping Gd-DTPA and (18)F-FDG for simultaneous PET/MRI acquisitions.

    PubMed

    Vecchione, Donatella; Aiello, Marco; Cavaliere, Carlo; Nicolai, Emanuele; Netti, Paolo Antonio; Torino, Enza

    2017-09-01

    Although there has been an improvement in the hardware and software of the PET/MRI system, the development of the nanoprobes exploiting the simultaneous acquisition of the bimodal data is still under investigation. Moreover, few studies on biocompatible and clinically relevant probes are available. This work presents a core-shell polymeric nanocarrier with improved relaxometric properties for simultaneous PET/MRI acquisitions. Core-shell nanoparticles entrapping the Gd-DTPA and (18)F-FDG are obtained by a complex coacervation. The boosting of r1 of the entrapped Gd-DTPA up to five-times compared with 'free Gd-DTPA', is confirmed by the PET/MRI scan. The sorption of (18)F-FDG into the nanoparticles is studied and designed to be integrated downstream for the production of the tracer.

  8. Evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapy agent targeting VEGF expressing cancers.

    PubMed

    Kameswaran, Mythili; Pandey, Usha; Gamre, Naresh; Vimalnath, K V; Sarma, Haladhar Dev; Dash, Ashutosh

    2016-08-01

    This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0±0.6%. In vitro stability was retained upto 4 days at 37°C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Spontaneous Intracranial Hypotension With Site of Leak Detected Only After 111In-DTPA Cisternogram.

    PubMed

    Parsian, Sana; Matesan, Manuela C; Kumbhar, Sachin Shivaji; Lewis, David H

    2017-04-01

    A 54-year-old man with a 3-week history of orthostatic headache and acute on chronic subdural hematoma presented with imaging findings suggestive of spontaneous intracranial hypotension. Three myelograms were negative for leak, and nontargeted epidural blood patches did not result in symptom relief. A cerebrospinal fluid leak study using In-DTPA with SPECT/CT demonstrated a focal area of asymmetric activity at the left C2 nerve root. A left C2 root tie-off, targeted epidural blood patch, and Dura seal glue resulted in resolution of patient symptomatology highlighting the importance of fused SPECT/CT images in detection of an occult cerebral spinal fluid leak.

  10. Extrarenal abnormalities in Tc-99m-DTPA renal blood flow studies

    SciTech Connect

    Shih, W.J.; Domstad, P.A.; DeLand, F.H.

    1985-01-01

    The authors observed extrarenal abnormalities during renal flow scintigraphy and retrospectively reviewed 90 patient studies to determine the types and frequencies of such abnormal findings. For each routine Tc-99m-DTPA renal flow study, they obtained nine 2-second sequential images, which included the heart, abdominal aorta, spleen and kidneys. Eighty abnormalities, observed in 62 patients, were divided into three categories: aortic, 37 cases; splenic, 40 cases; and miscellaneous, 3 cases. Other correlative studies including Tc-99m sulfur colloid-spleen scintigraphy, ultrasonography (US), CT, aortography, and surgical and/or autopsy findings were available for corroboration in 56 of 80 lesions.

  11. Evaluation of Focal Liver Reaction after Proton Beam Therapy for Hepatocellular Carcinoma Examined Using Gd-EOB-DTPA Enhanced Hepatic Magnetic Resonance Imaging

    PubMed Central

    Yamamoto, Kazutaka; Maeda, Yoshikazu; Kawamura, Mariko; Shibata, Satoshi; Sato, Yoshitaka; Terashima, Kazuki; Shimizu, Yasuhiro; Tameshige, Yuji; Sasaki, Makoto; Asahi, Satoko; Kondou, Tamaki; Kobayashi, Satoshi; Matsui, Osamu; Gabata, Toshifumi

    2016-01-01

    Background Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC. Material and Methods Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area. Results FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months. Conclusion This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT. PMID:27907063

  12. Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure.

    PubMed

    Petersen, L J; Petersen, J R; Talleruphuus, U; Møller, M L; Ladefoged, S D; Mehlsen, J; Jensen, H A

    1999-07-01

    The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea. Fifty patients with reduced renal function (serum creatinine between 150 and 600 micromol/l) were enrolled in the study. GFR was estimated from the uptake phase of 99mTc-DTPA renography (GFR(DTPA)). The renal clearance of 51Cr-EDTA (GFR(EDTA)) was used as the reference method. Creatinine clearance (C(Cr)), urea clearance (C(Ur)) and the mean of urea and creatinine clearance (C(Cr+Ur)/2) were also calculated from urine collected during a period of 24 h. Limits of agreement were used for method comparison. The limit of agreement between GFR(DTPA) and GFR(EDTA) was 2 +/- 17 ml/min. The mean difference did not deviate significantly from zero. The other clearance techniques had larger limits of agreement and a mean difference significantly different from zero. Furthermore, C(Ur) and C(Cr+Ur)/2 had systematic deviations of the differences, indicating that C(Ur) and C(Cr+Ur)/2 are poor estimates of GFR. The limit of agreement between GFR(DTPA) and GFR(EDTA) are acceptable and, therefore, GFR estimated from 99mTc-DTPA renography is acceptable for clinical use in patients with reduced renal function. Furthermore, the method is simple and less time consuming compared with renal clearance techniques.

  13. Spatial heterogeneity of DTPA-extractable zinc in cultivated soils induced by city pollution and land use.

    PubMed

    Jiang, Yong; Liang, Wenju; Wen, Dazhong; Zhang, Yuge; Chen, Wenbo

    2005-05-01

    The spatial heterogeneity of DTPA-extractable zinc in the cultivated soils of Shenyang suburbs in Liaoning Province of China was investigated, and its map was drawn by the methods of geostatistics combined with geographic information system. The data of soil DTPA-extractable zinc fitted normal distribution after logarithm transformation, and its semivariogram fitted a spherical model. The semivariogram indicated that the spatial dependence of soil DTPA-extractable zinc content was moderate, with the spatial dependence range of 1.69 km and the fractal dimension of 1.96. Stochastic factors contributed to 49.9% of the spatial variability, while structural factors contributed to 50.1% of it. The spatial heterogeneity of soil DTPA-extractable zinc shown by a kriged interpolation map was deeply influenced by stochastic factors such as city pollution, land use pattern and crop distributions. For example, the average content of Zn in vegetable garden soils was 2.5-4 times as much as in their originated soils, and was lower in paddy soils than in their originated soils. The areas with a higher content of soil DTPA-extractable zinc appeared in the near suburbs and the riverside along Hunhe River and the wastewater drainage of Xihe River, and the extremely high values in the near suburb of the city's residential area were a striking feature, indicating the key role of city pollution in the spatial heterogeneity of soil DTPA-extractable zinc. When recorded in the form of a soil pollution map, the results of such a survey make it possible to identify the unusually polluted areas, and to provide more information for precise agriculture and environmental control.

  14. Effect of DTPA on concentration ratios of /sup 237/Np and /sup 244/Cm in vegetative parts of bush bean and barley

    SciTech Connect

    Romney, E.M.; Wallace, A.; Mueller, R.T.; Cha, J.W.; Wood, R.A.

    1981-07-01

    We grew bush beans, barley, and rice in two different soils in a glasshouse with /sup 237/Np or /sup 244/Cm mixed into separate containers of the soil. The chelating agent DTPA at 100 ..mu..g/g soil was added to half of the containers. The concentration ratio (CR) for /sup 237/Np without DTPA was two orders of magnitude higher than for /sup 244/Cm without DTPA for all three plant species. The DTPA increased the CR of /sup 244/Cm by two to three orders of magnitude, but had no influence on that for /sup 237/Np. In bush beans, both /sup 237/Np and /sup 244/Cm CRs were higher in primary leaves than in trifoliate leaves, which were higher than for stems. The CRs for bush beans were generally higher for both /sup 237/Np and /sup 244/Cm than for either barley or rice, especially without DTPA.

  15. [Effect of the chelator Zn-DTPA on the excretion of lead in lead intoxication mice detected with ICP-MS].

    PubMed

    Li, Chen; Lu, Kai-zhi; Zhou, Qi; Wang, Qiong; Zeng, Yu-liang; Yin, Hong-jun; He, Xuan-hui; Tian, Ying; Dong, Jun-Xing

    2014-11-01

    To study the lead excretion effect of the chelator Zn-DTPA on the lead intoxication mice, inductively coupled plasma mass spectrometry (ICP-MS) was applied to detect the lead content of biological samples. The acute lead intoxication mice model was established by injecting lead acetate intraperitoneally with the dose of 1 mg. Zn-DTPA was administered intraperitoneally to mice once daily for five consecutive days 4 h after intoxication. Control group, model group, combination of Zn-DTPA and Ca-DTPA group were evaluated at the same time. The urine was collected every day. The mice were sacrificed in batches in the 2rd, 4th, 6th day. Biological samples including urine, whole blood, femur and brain were prepared and nitrated. Lead concentration was detected by ICP-MS. The result showed that Zn-DTPA could increase lead content in urine markedly and reduce lead content in blood, femur and brain.

  16. REPEATABILITY AND RELIABILITY OF GLOMERULAR FILTRATION RATE DETERMINATION VIA GAMMA CAMERA UPTAKE OF TC-99M-DTPA IN CATS WITH CHRONIC KIDNEY DISEASE.

    PubMed

    Felumlee, Amy E; Marolf, Angela J; Randall, Elissa K; Bachand, Annette M; Quimby, Jessica M

    2017-01-01

    Measurement of glomerular filtration rate (GFR) via gamma camera uptake of 99mTc-diethylenetriaminepentaacetic acid is a standard method for quantifying renal function. Aims of this retrospective, observer agreement study were to determine intra- and interobserver variation in GFR values for cats with chronic kidney disease and to determine whether renal insufficiency classification changed between observers. Guideline cut-points were established for the difference in repeated GFRs to differentiate changes caused by therapeutic effect vs. inherent variation. Included cats had a diagnosis of chronic kidney disease and had undergone GFR examinations between the years of 2010 and 2013. Twenty-nine GFR studies were sampled. Each study was read twice, 6 months apart, by two veterinary radiologists and one radiology resident. Modified Bland-Altman plots were used to investigate differences between readings 1 and 2 by observer and between pairs of observers by reading. Reliability of clinical classification was assessed through comparisons between readings and observers. Measurements were not systematically different between readings for the experienced observers but were higher in reading 1 than reading 2 for the inexperienced observer. Measurements were not systematically different between the experienced observers in reading 1 or between any two observers in reading 2. Reliability for GFR measurements was high among experienced observers; variations in GFR measurements rarely led to differences in clinical classification. Results suggested that, for experienced observers, changes in GFR values following treatment in cats with chronic kidney disease between -0.4 and 0.4 mL/min/kg may be due to inherent variability rather than treatment effect. © 2016 American College of Veterinary Radiology.

  17. Immunological persistence in 5 y olds previously vaccinated with hexavalent DTPa-HBV-IPV/Hib at 3, 5, and 11 months of age.

    PubMed

    Silfverdal, Sven A; Assudani, Deepak; Kuriyakose, Sherine; Van Der Meeren, Olivier

    2014-01-01

    The combined diphtheria-tetanus-acellular pertussis-hepatitis B-poliomyelitis/Haemophilus influenza vaccine (DTPa-HBV-IPV/Hib: Infanrix™ hexa, GlaxoSmithKline Vaccines) is used for primary vaccination of infants in a range of schedules world-wide. Antibody persistence after 4 DTPa-HBV-IPV/Hib doses in the first 2 y of life has been documented, but long-term persistence data following the 3, 5, 11-12 months (3-5-11) infant vaccination schedule, employed for example in Nordic countries, are limited. We assessed antibody persistence in 57 5-year-old children who had received either DTPa-HBV-IPV/Hib or DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in the 3-5-11 schedule. Among DTPa-HBV-IPV/Hib recipients, 7/12 retained seroprotective antibody concentrations for diphtheria, 10/12 for tetanus, 5/12 for hepatitis and 10/12 for Hib. Detectable antibodies were observed for 0/12 children for pertussis toxin (PT), 12/12 for filamentous haemagglutinin (FHA) and 8/12 for pertactin (PRN). Among DTPa-IPV/Hib recipients, 28/45 retained seroprotective anti-diphtheria concentrations, 34/44 for tetanus and 40/45 for Hib. Detectable antibodies were observed for 9/45 children for PT, 41/45 for FHA and 34/45 for PRN. Antibody persistence in DTPa-HBV-IPV/Hib and DTPa-IPV/Hib-vaccinees appeared similar in 5 y olds to that previously observed in children of a similar age who had received 4 prior doses of DTPa-HBV-IPV/Hib (or DTPa-IPV/Hib). As in subjects primed with 4 prior doses, we observed that antibodies markedly declined by 5 y of age, calling for the administration of a pre-school booster dose in order to ensure continued protection against pertussis.

  18. Influence of mixed-ligand complexes on retention and distribution of radioniobium in mice

    SciTech Connect

    Gachalyi, A.; Namenyi, J.; Szegedi, I.; Varga, L.P.

    1987-11-01

    The individual effects of desferrioxamine B (DFOA), Na3Ca diethylenetriaminepentaacetic acid (DTPA), Na-salicylate, DL-penicillamine, and 2-aminoethylisothiouronium bromide hydrobromide, as well as the effect of mixed-ligand treatment on the retention and elimination of /sup 95/Nb in mice have been examined. It was found that /sup 95/Nb could easily be mobilized by a single dose of DFOA, but the best result was obtained with the DFOA and DTPA combination. Mixed-ligand treatment did not change the deposition characteristics and translocation kinetics of /sup 95/Nb.

  19. Safety and efficacy parameters in patients treated with TiN-117m DTPA

    SciTech Connect

    Atkins, H.L.; Srivastava, S.C.; Meinken, G.E.

    1997-05-01

    We determined factors related to the administered dose versus efficacy and hematological toxicity in patients treated with Sn-117m DTPA for palliation of metastatic bone pain. We collected data in 47 patients (50 administrations) given Sn-117m DTPA in a dose escalation trial (5, 10, 12.5, 16, and 20 mCi/70/kg) for alleviation of pain from bone metastases derived from a variety of primary cancers. We correlated administered activity per unit body weight and calculated marrow dose, with both percent and absolute decrease in WBC and platelet counts, percent pain response, and onset of pain relief. We also correlated pain response with the extent of disease, using degree of uptake of tracer in bone and the bone index. At 5-20 mCi/70 kg dose levels, Sn-117m appears to have less hematological toxicity than other bone pain palliation agents (p<0.05). Overall pain relief (75%) was not correlated with administered activity and is similar to the other agents. There was a good correlation (p<0.05) between low and high levels of administered dose with response onset.

  20. Influence of complexans (EDTA, DTPA) on the toxicity of Cadmium to fish at chronic levels

    SciTech Connect

    Muramoto, S.

    1981-05-01

    There are a few reports on the effects of the complexing agents, as heavy metal pollution-inhibiting agents, to the aquatic animals. SPRAGUE(1968) reported on the influence of NTA on the zinc-and copper poisoning to brook trout. NISHIKAWA and TABATA(1969) conducted some experiments on eliminations of the toxicity of waste water from copper mines with EDTA using water fleas and dace. However, this in an area which has not so far as been clarifies in investigations on metal complexan toxicity and accumulation. In the previous paper, the effects of complexans(EDTA,NTA, and DTPA) on the metal-toxicity(Cd,Cu,Zn and Pb) at lethal levels and of complexan(EDTA) on the removing cadmium from the Cd-polluted fish were reported. This reports is examination of influence of complexans (EDTA and DTPA) on the metal toxicity and on the metal accumulation in viscera, gills and other parts of the fish exposing cadmium at low concentrations, long term(3 months). Vertebrae deformed fish induced by cadmium were observed with eye. The vertebrae of the fish were then examined by x-ray photography.

  1. Clinical experience with technetium-99m DTPA aerosol with perfusion scintigraphy in suspected pulmonary embolism

    SciTech Connect

    Selby, J.B.; Gardner, J.J.

    1987-01-01

    To evaluate the clinical value of radioaerosol imaging, 156 patients with suspected pulmonary embolism (PE) were studied. In 25 patients, a preperfusion xenon-133 (Xe-133) study was compared with a postperfusion study using Tc-99m DTPA aerosol. It was found that they were of equal value most of the time (56%), but that the aerosol study was more often helpful. Because of this, and the technical ease of using six standard views with radioaerosol, the series was completed using perfusion scintigraphy followed by radioaerosol images. In 19 patients the perfusion scintigraphy with Tc-99 macroaggregated albumin (Tc-99m MAA) was normal or nearly normal and no aerosol study was required. Tc-99m DTPA aerosol images were satisfactory when the count rate was at least twice and preferably three times that of the previous perfusion study. There were 17 studies (11%) classified as intermediate. There were 26 patients classified as high probability for PE, and angiographic or autopsy correlation was available in 14. All of the 14 proved to have PE. In the 113 patients classified as low probability, there were ten with angiographic or autopsy correlation. In the ten, there was one patient with a small pulmonary embolus found at autopsy. Clinical follow-up for over two months confirmed the absence of PE in the remainder of this group. Aerosol studies have proven technically easier to perform and a satisfactory substitute for xenon imaging in suspected PE.

  2. New normal values not related to age and sex, of glomerular filtration rate by (99m)Tc-DTPA renal dynamic imaging, for the evaluation of living kidney graft donors.

    PubMed

    Zhao, Xiuyi; Shao, Yahui; Wang, Yanming; Tian, Jun; Sun, Ben; Ru, Yanhui; Zhang, Aimin; Hao, Junwen

    2012-01-01

    The aim of this study was to investigate the normal values of glomerular filtration rate (GFR) by technetium-99m diaethylene-triamine-pentaacetic acid ((99m)Tc-DTPA) renal dynamic imaging for living kidney graft donors. In a total of 212 candidate donors, GFR was examined using (99m)Tc-DTPA renal dynamic imaging. Donors with GFR≥80mL/(min×1.73m(2)) and as low as with GFR≥70mL/(min×1.73m(2)) but a normal endogenous creatinine clearance rate (CCr) were quantified for living kidney donation. Differences in GFR levels based on sex and age were analyzed using rank correlation coefficient. Out of the 212 candidates, 161 were finally selected as kidney graft donors. The double kidney total GFR between the male and female donor groups, the GFR levels among differently-aged donor groups, and the GFR levels between the elderly (>55 years) and young- and middle-aged (≤55 years) donor groups did not show any significant difference (P>0.05). After kidney donation, renal function measured by blood urea nitrogen (BUN) and serum creatinine of all donors returned to normal within one week, and no serious complications were noticed. In conclusion, renal dynamic imaging by (99m)Tc-DTPA had a good accuracy and repeatability in GFR evaluation for living kidney donors. Candidate donors with GFR between 70mL/(min×1.73m(2)) and 80mL/(min×1.73m(2)) can be selected as kidney donors after strict screening. In living kidney donors GFR is not significantly correlated with age or sex.

  3. Diagnostic Accuracy of Gd-EOB-DTPA for Detection Hepatocellular Carcinoma (HCC): A Comparative Study with Dynamic Contrast Enhanced Magnetic Resonance Imaging (MRI) and Dynamic Contrast Enhanced Computed Tomography (CT)

    PubMed Central

    Imbriaco, Massimo; De Luca, Serena; Coppola, Milena; Fusari, Mario; Klain, Michele; Puglia, Marta; Mainenti, Pierpaolo; Liuzzi, Raffaele; Maurea, Simone

    2017-01-01

    Summary Background To compare the diagnostic accuracy of hepato-biliary (HB) phase with gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) with dynamic contrast-enhanced MR imaging (DCEMRI) and contrast-enhanced CT (DCECT) for hepatocellular carcinoma (HCC) detection. Material/Methods 73 patients underwent DCECT and Gd-EOB-DTPA-3T-MR. Lesions were classified using a five-point confidence scale. Reference standard was a combination of pathological evidence and tumor growth at follow-up CT/MR at 12 months. Receiver Operating Characteristic (ROC) curves were obtained. Results A total of 125 lesions were confirmed in 73 patients. As many as 74 were HCCs and 51 were benign. Area under the curve (AUC) was 0.984 for DCEMRI+HB phase vs. 0.934 for DCEMRI (p<0.68) and 0.852 for DCECT (p<0.001). For lesions >20 mm (n.40), AUC was 0.984 for DCEMRI+HB phase, 0.999 for DCEMRI, and 0.913 for DCECT, (p=n.s.). For lesions <20 mm (n.85) AUC was 0.982 for DCEMRI+HB phase vs. 0.910 for DCEMRI (p<0.01) and 0.828 for DCECT (p<0.001). Conclusions The addition of HB phase to DCEMRI provides an incremental accuracy of 4.5% compared to DCEMRI and DCECT for HCC detection. The accuracy of Gd-EOB-DTPA-3T-MR significantly improves for lesions <20 mm. No significant improvement is observed for lesions >20 mm and patients with Child-Pugh class B or C. PMID:28217239

  4. Passive and active hepatoma tumor targeting of new N-(2-hydroxypropyl)methacrylamide copolymer conjugates: synthesis, characterization, and evaluation in vitro and in vivo.

    PubMed

    Yuan, Jianchao; Yuan, Bingnian; Guo, Hongyun; Zeng, Xianwu; Wang, Xiaoqi; Liao, Shiqi; Li, Jing; Jia, Zong; Song, Fengying; Wang, Fuzhou

    2013-01-01

    Human hepatocellular carcinoma (HCC) is one of the major causes of death worldwide. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific sulfapyridine HPMA (HPMA: N-(2-hydroxypropyl methacrylamide)) copolymer (sulfapyridine: SPD) conjugates, nonspecific HPMA copolymer conjugates, and DTPA are described in this study. The poly(HPMA)-SPD-DTPA (DTPA: diethylenetriaminepentaacetic acid), poly(HPMA)-DTPA, and DTPA conjugates were radiolabeled with the radionuclide (99m)Tc and tested for uptake by cultured H22 cells. The cellular accumulation of poly(HPMA)-SPD-DTPA-(99m)Tc complex was found to be time-dependent. The poly(HPMA)-SPD-DTPA-(99m)Tc tracer exhibited rapid uptake kinetics in cell culture with a t(1/2) of ~5 min. The uptake of poly(HPMA)-SPD-DTPA-(99m)Tc was significantly higher than that of poly(HPMA)-DTPA-(99m)Tc, indicating that the uptake of the poly(HPMA)-SPD-DTPA-(99m)T was active binding. The uptake of poly(HPMA)-DTPA-(99m)Tc was significantly higher than that of DTPA-(99m)Tc, suggesting that the uptake of the poly(HPMA)-DTPA-(99m)T was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p < 0.001) tumor localization for poly(HPMA)-SPD-DTPA-(99m)Tc (4.98 ± 0.48%ID/g [percentage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-(99m)Tc (2.69 ± 0.15% ID/g) and DTPA-(99m)Tc (0.83 ± 0.03%ID/g). Moreover, higher T/B for poly(HPMA)-SPD-DTPA-(99m)Tc indicated reduced extravazation of the targeted polymeric conjugates in normal tissues. Specific molecular targeting and nonspecific vascular permeability are both significant in the relative tumor localization of poly(HPMA)-SPD-DTPA-(99m)Tc. Extravascular leak in nonspecific organs appears to be a major factor in reducing the T/B for the sulfapyridine molecules. Thus, the poly(HPMA)-SPD-DTPA is expected to be used

  5. Utility of radioisotopic filtration markers in chronic renal insufficiency: Simultaneous comparison of sup 125 I-iothalamate, sup 169 Yb-DTPA, sup 99m Tc-DTPA, and inulin. The Modification of Diet in Renal Disease Study

    SciTech Connect

    Perrone, R.D.; Steinman, T.I.; Beck, G.J.; Skibinski, C.I.; Royal, H.D.; Lawlor, M.; Hunsicker, L.G. )

    1990-09-01

    Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time-consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc-DTPA, 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m-2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects.

  6. Development of 153Sm-DTPA-SPION as a theranostic dual contrast agents in SPECT/MRI

    PubMed Central

    Gholami, Amir; Mousavie Anijdan, Seyyed Hossein

    2016-01-01

    Objective(s): This study describes the preparation, biodistribution of 153Sm-DTPA-SPION after intravenous injection in rats. Materials and Methods: The chelator DTPA dianhydride was conjugated to SPION using a small modification of the well-known cyclic anhydride method. Conjugation was done at a 1: 4 (SPION:ccDTPA) molar ratio. Conjugation reaction was purified with magnetic assorting column (MACs) using high gradient magnetic field following incubation, the radio labeled conjugate was checked using RTLC method for labeling and purity checked. Results: The RTLC showed that labeling yield was above 99% after purification and the compound have good in vitro stabilities until 48 hr post injection in the presence of human serum. The biodistribution of 153Sm-DTPA-SPION in rats showed dramatic uptake in the reticuloendothelial system (RES) and their clearance is so fast in other organs especially in the blood. Biodistribution results show that after 30 min post injection more than 84% of injected activities were taken up by the liver and spleen (about 64% and 20%, respectively). Conclusion: Due to magnificent uptakes of this radiotracer in the liver and spleen and their fast clearance from other tissues, especially in blood, it is suggested that this radiotracer would be a potential candidate for RES theranostic purposes. PMID:27872701

  7. Pneumocystis pneumonia increases the clearance rate of inhaled /sup 99m/Tc DTPA from lung to blood

    SciTech Connect

    Jones, D.K.; Higenbottam, T.W.

    1985-10-01

    Despite no radiographic change, a patient with Pneumocystis pneumonia showed increased clearance of inhaled /sup 99m/Tc DTPA from lung to blood. Gas transfer for carbon monoxide was also reduced, but improved with treatment. This was paralleled by serial increase in the t1/2 LB.

  8. Identification of complexes involving Tl(I) and Tl(III) with EDTA and DTPA ligands by ESI-MS.

    PubMed

    Zembrzuska, Joanna; Karbowska, Bozena

    2017-08-21

    Thallium is considered as an environmental threat, however its hazardous properties depend on its oxidation state. Tl(III) is approx. 1000-times more toxic compared to Tl(I), therefore identification of each species is essential in order to properly evaluate the associated health hazard. ESI-MS allows determination of speciation in solution due to its soft mode of ionization while selective complexation with ligands allows to distinguish the Tl species. Selective complexation of Tl(I) and Tl(III) ions requires the use of two selective complexing agents and selection of appropriate conditions for this process. Tl(I) and Tl(III) ions as well as two ligands (EDTA and DTPA) were used to form binary (single ion + single ligand), ternary (one ion + both ligands) and quaternary systems (both ions and both ligands) under different pH conditions (7 and 8). These mixtures were subjected to the determination of Tl species using ESI-MS operating in positive and negative ion mode. Tl(I) complexes with DTPA were identified at pH 7 and 8, whereas in case of EDTA the complexes were detected only at pH 8. In contrast, Tl(III) formed distinct complexes with EDTA at pH 7 and 8, while with DTPA the complexes were detected only at pH 8. Analysis of the quaternary system (which contained both ions and both ligands) revealed that Tl(I) formed complexes with EDTA, while Tl(III) formed complexes with DTPA at pH 7 and 8. The obtained results confirmed that the increase of the solution complexity allowed to simultaneously identify different complexes is solutions containing both Tl species. The initial analyzes carried out for binary and ternary solutions facilitated the simultaneous determination of specific complexes (Tl(I) with EDTA and Tl(III) with DTPA) in the quaternary system. This article is protected by copyright. All rights reserved.

  9. Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

    2012-05-01

    This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×109 MBs ml-1 using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C3F8) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd3+ ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T1-weighted turbo-spin-echo sequence MR imaging. Heavy T2*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2- and T2*-weighted MR images. The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35 s-1mM-1, respectively, indicating that the MBs represent a positive contrast agent in T1-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for

  10. Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging.

    PubMed

    Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

    2012-05-07

    This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual

  11. Theoretical investigation of fluorescence properties of EDTA and DTPA substituted tetraphenylporphyrin molecules

    NASA Astrophysics Data System (ADS)

    Valiev, R. R.; Kalugina, Yu. N.; Cherepanov, V. N.

    2012-12-01

    The matrix elements of spin-orbit coupling operator (HSO) and non-adiabatic coupling operator (Ω) for the H2ATPP-EDTA and H2ATPP-DTPA molecules were calculated using INDO method. Rate constants of internal conversion and of intersystem crossing were calculated using the values of matrix elements of HSO and Ω operators and excitation energies both calculated with the ADC(2) and TDDFT methods and obtained from experimental data. Results of calculations show that the probability of radiationless deactivation in internal conversion channel is greater than the probability of radiationless transition in intersystem crossing channel for considered molecules. Obtained theoretical values of fluorescence quantum yield have good agreement with their experimental values.

  12. Ozone-induced changes in the pulmonary clearance of (99m)Tc-DTPA in man

    SciTech Connect

    Kehrl, H.R.; Vincent, L.M.; Kowalsky, R.J.; Horstman, D.H.; O'Neil, J.J.

    1988-05-01

    Ozone is a respiratory irritant that has been shown in animals to increase the premeability of the respiratory epithelium. In the study the authors have recently reported that respiratory epithelial permeability was similarly affected in eight healthy non-smoking young men exposed to ozone (ARRD, 135 (1987) 1124-8). Permeability was evaluated by determining the pulmonary clearance of inhaled aerosolized 99mTc-DTPA with sequential posterior lung imaging by a computer-assisted gamma camera. In a randomized crossover design, 16 young men were exposed for 2 h to purified air and 0.4 ppm ozone while performing intermittent high intensity treadmill exercise; forced vital capacity (FVC) was measured before and at the end of exposures. The results demonstrate that ozone exposure increased respiratory epithelial permeability. Such an increase may be a manifestation of direct ozone-induced epithelial-cell injury, lung inflammation, or both.

  13. Synthesis and biological assessment of folate-accepted developer (99m)Tc-DTPA-folate-polymer.

    PubMed

    Chen, Fei; Shao, Kejing; Zhu, Bao; Jiang, Mengjun

    2016-05-15

    A novel cancer-targetable folate-poly(2-hydroxyethyl methacrylate) (PFDH) copolymer containing DTPA segment was prepared by conventional chemical synthesis and labeled with (99m)Tc subsequently. The (99m)Tc-labled PFDH could be produced easily with high radiochemical yield of 91% and radiochemical purity of 95%. The LogP octanol-water value for the (99m)Tc-labled PFDH was -2.19 and the radiotracer was stable in phosphate-buffered saline and human serum for 2h (>95% in PBS or ∼90% in human serum). To investigate (99m)Tc-labled PFDH tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and SPECT imaging were evaluated, respectively. These preliminary results strongly suggest that the novel folate conjugated dendrimer maybe developed to be potential for delivery of therapeutic radionuclides.

  14. Tin-117m(4+)-DTPA for palliation of pain from osseous metastases: A pilot study

    SciTech Connect

    Atkins, H.L.; Mausner, L.F.; Srivastava, S.C. ||

    1995-05-01

    The physical and biological attributes of {sup 117m}Sn(4+)-DTPA indicate that it should be an effective agent for palliative therapy of painful bony metastatic disease. The aim of this study was to evaluate whether or not this agent could effectively reduce pain while sparing the hemopoietic marrow from adverse effects. Fifteen patients (10 males and 5 females) with painful bony metastases from various primary cancers were included in the study. Seven patients received 1.22 to 3.11 MBq/kg of {sub 117m}Sn intravenously (Group 1) and eight patients received 4.85 to 5.77 MBq/kg (Group 2). All but one were treated as outpatients and followed for a minimum of 2 mo. In the first group, pain relief was nonassessable in four patients because of death or additional treatment of soft-tissue disease by another modality. One patient had no relief of pain, one had complete relief of pain and one had transient relief of pain. No myelotoxicity was observed. For Group 2, three patients achieved complete relief of pain, two good relief, two partial relief and one began to experience pain relief when he suffered a pathological fracture 2 mo most-treatment. None of these patients had myelotoxicity. Tin-117m(4+)-DTPA can reduce pain from metastatic disease to bone without inducing adverse reactions related to bone marrow. Further studies are needed to assess tolerance levels for the bone marrow and to evaluate response rates and duration of effect. 6 refs., 4 figs., 4 tabs.

  15. PET imaging of HER1-expressing xenografts in mice with 86Y-CHX-A”-DTPA-cetuximab

    PubMed Central

    Nayak, Tapan K.; Regino, Celeste A.S.; Wong, Karen J.; Milenic, Diane E.; Garmestani, Kayhan; Baidoo, Kwamena E.; Szajek, Lawrence P.; Brechbiel, Martin W.

    2010-01-01

    Cetuximab is a recombinant, human/mouse chimeric IgG1, monoclonal antibody (mAb) that binds to the epidermal growth factor receptor (EGFR/HER1). Cetuximab is approved for the treatment of patients with HER1-expressing metastatic colorectal cancer. Limitations in currently reported radiolabeled cetuximab for PET applications prompted the development of 86Y-CHX-A”-DTPA-cetuximab as an alternative for imaging HER1-expressing cancer. 86Y-CHX-A”-DTPA-cetuximab can also serve as a surrogate marker for 90Y therapy. Methods Bifunctional chelate, CHX-A”-DTPA was conjugated to cetuximab and radiolabeled with 86Y. In vitro immunoreactivity was assessed in HER1-expressing A431 cells. In vivo biodistribution, PET imaging and non-compartmental pharmacokinetics were performed on mice bearing HER1-expressing human colorectal (LS-174T and HT29), prostate (PC-3 and DU145), ovarian (SKOV3) and pancreatic (SHAW) tumor xenografts. Receptor blockage was demonstrated by co-injection of either 0.1 or 0.2 mg cetuximab. Results 86Y-CHX-A”-DTPA-cetuximab was routinely prepared with a specific activity of 1.5– 2 GBq/mg and in vitro immunoreactivity ranging from 65–75 %. Biodistribution and PET imaging studies demonstrated high HER1-specific tumor uptake of the radiotracer and clearance from non-specific organs. In LS-174T tumor bearing mice injected with the 86Y-CHX-A”-DTPA-cetuximab alone, 86Y-CHX-A”-DTPA-cetuximab plus 0.1 mg cetuximab or 0.2 mg cetuximab, the tumor uptake values at 3 d were 29.3 ± 4.2, 10.4 ± 0.5 and 6.4 ± 0.3 % ID/g, respectively, demonstrating dose-dependent blockage of the target. Tumors were clearly visualized 1 d after injecting 3.8–4.0 MBq 86Y-CHX-A”-DTPA-cetuximab. Quantitative PET revealed highest tumor uptake in LS-174T (29.55 ± 2.67 % ID/cc) and lowest tumor uptake in PC-3 (15.92 ± 1.55 % ID/cc) xenografts at 3 d after injection. Tumor uptake values quantified by PET were closely correlated (r2= 0.9, n=18) to values determined by

  16. Binding Specificity of Radiolabeled Cyclic Peptide 153Sm-DTPA-c(CGRRAGGSC) to MHCC97-H Human Liver Cancer Cells and its Antitumor Effects in vivo.

    PubMed

    Wu, Qinghua; He, Yujie; Gu, Chen; Jiang, Jianwei; Zhou, Huan; Zhou, Shi

    2016-12-01

    This objective of this study is to investigate the effects of the radiolabeled cyclic peptide (153)Sm-DTPA-c(CGRRAGGSC) on MHCC97-H human liver cancer cells in vitro and in vivo. The protein expression levels were examined by Western blot analysis. Biological activity of (153)Sm-DTPA-c(CGRRAGGSC) was assessed with the radioligand binding assay and competitive inhibition experiment. Subcellular localization of the cyclic peptide was observed by fluorescence microscopy. Animals were implanted with MHCC97-H cells and administered with (153)Sm-DTPA-c(CGRRAGGSC). Hematoxylin and eosin staining, electron microscopy, and immunohistochemistry were performed to evaluate the effects of (153)Sm-DTPA-c(CGRRAGGSC) on implanted tumors. The expression levels of interleukin 11 receptor were significantly elevated, by 2-to 5-fold, in tumor cell lines, especially for MHCC97-H cells. Characterization of (153)Sm-DTPA-c(CGRRAGGSC) showed that the biological activity of the cyclic peptide was not altered after labeling, and the radiolabeled cyclic peptide exhibited sufficient binding affinity to interleukin 11 receptor . The cyclic peptide of c(CGRRAGGSC) was mainly distributed in the cytoplasm and on the cell membrane of MHCC97-H cells. The in vivo experiments showed that the tumor growth was significantly inhibited by the treatment of (153)Sm-DTPA-c(CGRRAGGSC). The inhibitory effect of (153)Sm-DTPA-c(CGRRAGGSC) on tumor growth was further confirmed by Hematoxylin and eosin staining, electron microscopy, and immunohistochemistry. Moreover, the expression levels of interleukin 11 receptor in implanted tumors were significantly decreased in the treatment groups. (153)Sm-DTPA-c (CGRRAGGSC) could specifically bind to interleukin 11 receptor on MHCC97-H liver tumor cells, inhibiting the cell proliferation and inducing cellular apoptosis. These findings provide experimental evidence for the development of individual treatment of liver cancers, as well as recurrence and metastasis. © The

  17. Evaluation of cell tracking effects for transplanted mesenchymal stem cells with jetPEI/Gd-DTPA complexes in animal models of hemorrhagic spinal cord injury.

    PubMed

    Liu, Yu; He, Zhi-Jie; Xu, Bo; Wu, Qi-Zhu; Liu, Gang; Zhu, Hongyan; Zhong, Qian; Deng, David Y; Ai, Hua; Yue, Qiang; Wei, Yi; Jun, Shen; Zhou, Guangqian; Gong, Qi-Yong

    2011-05-19

    Cell tracking using iron oxide nanoparticles has been well established in MRI. However, in experimental rat models, the intrinsic iron signal derived from erythrocytes masks the labeled cells. The research evaluated a clinically applied Gd-DTPA for T1-weighted positive enhancement for cell tracking in spinal cord injury (SCI) rat models. MSCs were labeled with jetPEI/Gd-DTPA particles to evaluate the transfection efficiency by MRI in vitro. Differentiation assays were carried out to evaluate the differentiation ability of Gd-DTPA-labeled MSCs. The Gd-DTPA-labeled MSCs were transplanted to rat SCI model and monitored by MRI in vivo. Fluorescence images were taken to confirm the MRI results. Behavior test was assessed with Basso, Beattie, and Bresnahan (BBB) scoring in 6weeks after cell transplantation. The Gd-labeled MSCs showed a significant increase in signal intensity in T1-weighted images. After local transplantation, Gd-DTPA-labeled MSCs could be detected in SCI rat models by the persistent T1-weighted positive enhancement from 3 to 14days. Under electronic microscope, Gd-DTPA/jetPEI complexes were mostly observed in cytoplasm. Fluorescence microscopy examination showed that the Gd-labeled MSCs survived and distributed within the injured spinal cord until 2weeks. The Gd-labeled MSCs were identified and tracked with MRI by cross and sagittal sections. The BBB scores of the rats with labeled MSCs transplantation were significantly higher than those of control rats. Our results demonstrated that Gd-DTPA is appropriate for cell tracking in rat model of SCI, indicating that an efficient and nontoxic label method with Gd-DTPA could properly track MSCs in hemorrhage animal models.

  18. The Impact of Gd-Eob-Dtpa-Enhanced MR Cholangiography in Biliary Diseases: Comparison with T2-Weighted MR Cholangiopancreatography

    PubMed Central

    Özmen, Evrim; Algın, Oktay; Evrimler, Şehnaz; Arslan, Halil

    2016-01-01

    Background: Contrast enhanced magnetic resonance cholangiography is a novel technique and promising method in demonstrating biliary tree anatomy and evaluating biliary disorders. However, to date, there are a limited number of studies that have focused on the impact of this technique. Aims: We aimed to evaluate the additional role of contrast enhanced MR cholangiography (MRC) and compare contrast enhanced MRC with T2-weighted (w) magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of biliary disorders. Study Design: Diagnostic accuracy study. Methods: The T2w-MRCP and contrast enhanced MRC sequences of 31 patients whose gold standard test results were available were scored visually for the existence of pathological findings with regard to any of the biliary diseases. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) was used as the contrast agent. The correlation values were determined according to the statistical analysis made from those scores and the sensitivity, specificity and accuracy values of each sequence were detected as well. Results: We detected that the correlation values with gold standard methods of contrast enhanced MRC sequences were significantly higher than the ones of T2w-MRCP sequences. The correlation ratios of T2w-MRCP sequences were between 26 and 34%, while those for contrast enhanced MRC sequences were between 81 and 83% for the first reader and the correlation ratios of T2w-MRCP sequences were between 10 and 61%, whereas those of contrast enhanced MRC were between 79 and 81% for the second reader The mean sensitivity, specificity and accuracy values of T2w-MRCP sequences were 14.3–42.5%, 85–89.2% and 59.3–72.5%, respectively, while the mean sensitivity, specificity and accuracy values of contrast enhanced MRC sequences were 100%, 86.7% and 93.2–93.3%, respectively. Conclusion: We suggest that obtaining of contrast enhanced MRC sequences in addition to the T2w-MRCP can be useful in the

  19. Initial clinical evaluation of radiolabeled MX-DTPA humanized BrE-3 antibody in patients with advanced breast cancer.

    PubMed

    Kramer, E L; Liebes, L; Wasserheit, C; Noz, M E; Blank, E W; Zabalegui, A; Melamed, J; Furmanski, P; Peterson, J A; Ceriani, R L

    1998-07-01

    To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal antibody as a radioimmunolocalization and therapeutic agent in breast cancer patients, tumor localization, pharmacokinetics, radiation dosimetry, and immunogenicity of (111)In-labeled combined 1-p-isothiocyanatobenzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyldiethylenetriamine pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with BrE-3 antigen-positive, metastatic breast carcinoma underwent (111)In huBrE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for (111)In huBrE-3. Data were extrapolated to 90Y huBrE-3. Human anti-human antibody (HAHA) response was measured in serum samples obtained up to 3 months after infusion. Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T1/2alpha=10.6+/-8.5 (SD) h and average T1/2beta=114.2+/-39.2 h. Radiation absorbed dose estimates for (111)In huBrE-3 for whole body averaged 0.53+/-.08 rads/mCi. Dose estimates for 90Y huBrE-3 for marrow averaged 8.4+/-11.9 rads/mCi, and for tumors, 70+/-31.5 rads/mCi. Liver radioactivity uptake averaged 19.7+/-8.8% injected dose at 24 h after infusion, translating into an average radiation absorbed dose 21.1+/-12 rads/90Y mCi administered. Only one of seven patients demonstrated a low level of HAHA response. Although the plasma half-lives are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumor dosimetry, and low immunogenicity support the use of 90Y-huBrE-3 antibody for radioimmunotherapy of breast cancer.

  20. Aqueous complexation of thorium(IV), uranium(IV), neptunium(IV), plutonium(III/IV), and cerium(III/IV) with DTPA.

    PubMed

    Brown, M Alex; Paulenova, Alena; Gelis, Artem V

    2012-07-16

    Aqueous complexation of Th(IV), U(IV), Np(IV), Pu(III/IV), and Ce(III/IV) with DTPA was studied by potentiometry, absorption spectrophotometry, and cyclic voltammetry at 1 M ionic strength and 25 °C. The stability constants for the 1:1 complex of each trivalent and tetravalent metal were calculated. From the potentiometric data, we report stability constant values for Ce(III)DTPA, Ce(III)HDTPA, and Th(IV)DTPA of log β(101) = 20.01 ± 0.02, log β(111) = 22.0 ± 0.2, and log β(101) = 29.6 ± 1, respectively. From the absorption spectrophotometry data, we report stability constant values for U(IV)DTPA, Np(IV)DTPA, and Pu(IV)DTPA of log β(101) = 31.8 ± 0.1, 32.3 ± 0.1, and 33.67 ± 0.02, respectively. From the cyclic voltammetry data, we report stability constant values for Ce(IV) and Pu(III) of log β(101) = 34.04 ± 0.04 and 20.58 ± 0.04, respectively. The values obtained in this work are compared and discussed with respect to the ionic radius of each cationic metal.

  1. In vivo magnetic resonance imaging of atherosclerotic lesions with a newly developed Evans blue-DTPA-gadolinium contrast medium in apolipoprotein-E-deficient mice.

    PubMed

    Yasuda, Satoshi; Ikuta, Kenjiro; Uwatoku, Toyokazu; Oi, Keiji; Abe, Kohtaro; Hyodo, Fuminori; Yoshimitsu, Kengo; Sugimura, Kohtaro; Utsumi, Hideo; Katayama, Yoshiki; Shimokawa, Hiroaki

    2008-01-01

    Magnetic resonance imaging (MRI) contrast agents that specifically detect atherosclerotic plaque may be useful for the noninvasive detection of the plaque. We have recently developed a new contrast agent, Evans blue-DTPA-gadolinium (EB-DTPA-Gd), which selectively accumulates vascular lesions with endothelial removal. In this study, we examined whether EB-DTPA-Gd is also useful for in vivo imaging of atherosclerotic plaques. We used male apolipoprotein-E-deficient (ApoE-/-) mice of different ages (3, 6 and 12 months old) and age-matched male wild-type mice. After a single intravenous administration of EB-DTPA-Gd (160 microM/kg body weight), MRI T(1) signal was obtained in vivo. Increased signal intensity in the aortic wall was noted within 10-20 min after intravenous injection of EB-DTPA-Gd and was maintained for 30 min. The MRI enhancement in the aorta of ApoE-/- mice was increased in accordance with age, whereas no such enhancement was noted in wild-type mice. Histological examination demonstrated that there was a topological correlation between the site of MRI enhancement and that of atherosclerotic plaque. These results indicate that EB-DTPA-Gd is a useful MRI contrast medium for the in vivo detection of atherosclerotic plaques. Copyright (c) 2007 S. Karger AG, Basel.

  2. Comparison of methods for calculating glomerular filtration rate: Technetium-99m-DTPA scintigraphic analysis, protein-free and whole-plasma clearance of technetium-99m-DTPA and iodine-125-iothalamate clearance

    SciTech Connect

    Goates, J.J.; Morton, K.A.; Whooten, W.W.; Greenberg, H.E.; Datz, F.L.; Handy, J.E.; Scuderi, A.J.; Haakenstad, A.O.; Lynch, R.E. )

    1990-04-01

    True glomerular filtration rate (GFR) was measured in normal volunteers and in patients with normal and impaired renal function by the iothalamate clearance (IC) method of Sigman. Within 24 hr, GFR was also determined by two other methods: technetium-99m- ({sup 99m}Tc) DTPA scintigraphic analysis (SA) utilizing a modification of the Gates computer program, and by measuring disappearance of {sup 99m}Tc-DTPA from whole plasma (WPC) and from protein-free ultrafiltered plasma (PFPC). Determinations of GFR by IC and by PFPC methods were virtually identical (mean absolute error 5.36 ml/min, r = 0.99, p greater than 0.05). GFRs measured in protein-free, ultrafiltered plasma differed significantly from those obtained from whole plasma only in sicker patients and in those taking multiple medications (in whom alterations in protein-binding of DTPA may be seen). The SA method correlated less well with the iodine-125-({sup 125}I) IC method than did either the protein-free or whole-plasma clearance methods (mean absolute error 32.36 ml/min, r = 0.74, p less than 0.05). However, the SA method provided useful information with respect to differential (split) renal function.

  3. A novel contrast agent with rare earth-doped up-conversion luminescence and Gd-DTPA magnetic resonance properties

    NASA Astrophysics Data System (ADS)

    Lu, Qing; Wei, Daixu; Cheng, Jiejun; Xu, Jianrong; Zhu, Jun

    2012-08-01

    The magnetic-luminescent multifunctional nanoparticles based on Gd-DTPA and NaYF4:Yb, Er were successfully synthesized by the conjugation of activated DTPA and silica-coated/surface-aminolated NaYF4:Yb, Er nanoparticles through EDC/NHS coupling chemistry. The as-prepared products were characterized by powder X-ray diffraction, transmission electron microscopy, dynamic light scattering, energy dispersive X-ray analysis, and fourier transform infrared spectrometry. The room-temperature upconversion luminescent spectra and T1-weighted maps of the obtained nanoparticles were carried out by 980 nm NIR light excitation and a 3T MR imaging scanner, respectively. The results indicated that the as-synthesized multifunctional nanoparticles with small size, highly solubility in water, and both high MR relaxivities and upconversion luminescence may have potential usage for MR imaging in future.

  4. Assessment of effective absorbed dose of (111)In-DTPA-Buserelin in human on the basis of biodistribution rat data.

    PubMed

    Lahooti, Afsaneh; Shanehsazzadeh, Saeed; Jalilian, Amir Reza; Tavakoli, Mohammad Bagher

    2013-04-01

    In this study, the effective absorbed dose to human organs was estimated, following intra vascular administration of (111)In-DTPA-Buserelin using biodistribution data from rats. Rats were sacrificed at exact time intervals of 0.25, 0.5, 1, 2, 4 and 24 h post injections. The Medical Internal Radiation Dose formulation was applied to extrapolate from rats to humans and to project the absorbed radiation dose for various human organs. From rat data, it was estimated that a 185-MBq injection of (111)In-DTPA-Buserelin into the human might result in an estimated absorbed dose of 24.27 mGy to the total body and the highest effective absorbed dose was in kidneys, 28.39 mSv. The promising results of this study emphasises the importance of absorbed doses in humans estimated from data on rats.

  5. Physiological Uptake in the Pancreatic Head on Somatostatin Receptor Scintigraphy Using [111In-DTPA]Octreotide: Incidence and Mechanism.

    PubMed

    Brabander, Tessa; Teunissen, Jaap; Kwekkeboom, Dik

    2017-01-01

    Physiological uptake in the uncinate process or pancreatic head has been described with Ga-labeled PET tracers for somatostatin receptor imaging. In-DTPA-octreotide is the only registered radiopharmaceutical for the imaging of neuroendocrine tumors. We studied the uptake in this region of the pancreatic head on somatostatin receptor scintigraphy (SRS) using In-DTPA-octreotide in a large group of patients. Furthermore, known physiological and clinical characteristics are discussed in an attempt to elucidate this phenomenon. Four hundred seven patients underwent SRS using In-DTPA-octreotide in our department in 2014. After excluding patients with a known malignancy in or close to the pancreas, as well as all scans without SPECT/CT of the upper abdomen, we reviewed 178 scans in total. The uptake was graded on a 4-point scale that correlates the uptake in the pancreatic head to physiological uptake in the liver. Uptake in the region of the pancreatic head, including the uncinate process, was seen in 46 (26%) of 178 patients on SPECT/CT and in 12 patients (7%) on planar imaging. On SPECT/CT, uptake was lower than the liver in 26 patients (15%), equal to the liver in 17 patients (10%), and higher than the liver in 3 patients (2%). In patients with diabetes mellitus (DM), the incidence of uptake in the pancreatic head was 50% on SPECT/CT. Physiological uptake in the pancreatic head is seen on SPECT/CT with In-DTPA-octreotide in 26% of patients, and the incidence is doubled in patients with DM. Previous case reports showed uptake in the pancreatic head due to histologically proven pancreatic polypeptide (PP) cell hyperplasia. Also, patients with DM have elevated serum PP concentrations, which is likely due to PP cell hyperplasia. Because 90% of PP cells are present in the pancreatic head, PP cell hyperplasia is the most likely explanation for visualization of the pancreatic head on SRS in a substantial number of patients.

  6. Evaluation of a maleimido derivative of CHX-A'' DTPA for site-specific labeling of affibody molecules.

    PubMed

    Tolmachev, Vladimir; Xu, Heng; Wållberg, Helena; Ahlgren, Sara; Hjertman, Magnus; Sjöberg, Anna; Sandström, Mattias; Abrahmsén, Lars; Brechbiel, Martin W; Orlova, Anna

    2008-08-01

    Affibody molecules are a new class of small targeting proteins based on a common three-helix bundle structure. Affibody molecules binding a desired target may be selected using phage-display technology. An Affibody molecule Z HER2:342 binding with subnanomolar affinity to the tumor antigen HER2 has recently been developed for radionuclide imaging in vivo. Introduction of a single cysteine into the cysteine-free Affibody scaffold provides a unique thiol group for site-specific labeling of recombinant Affibody molecules. The recently developed maleimido-CHX-A'' DTPA was site-specifically conjugated at the C-terminal cysteine of Z HER2:2395-C, a variant of Z HER2:342, providing a homogeneous conjugate with a dissociation constant of 56 pM. The yield of labeling with (111)In was >99% after 10 min at room temperature. In vitro cell tests demonstrated specific binding of (111)In-CHX-A'' DTPA-Z 2395-C to HER2-expressing cell-line SKOV-3 and good cellular retention of radioactivity. In normal mice, the conjugate demonstrated rapid clearance from all nonspecific organs except kidney. In mice bearing SKOV-3 xenografts, the tumor uptake of (111)In-CHX-A'' DTPA-Z 2395-C was 17.3 +/- 4.8% IA/g and the tumor-to-blood ratio 86 +/- 46 (4 h postinjection). HER2-expressing xenografts were clearly visualized 1 h postinjection. In conclusion, coupling of maleimido-CHX-A'' DTPA to cysteine-containing Affibody molecules provides a well-defined uniform conjugate, which can be rapidly labeled at room temperature and provides high-contrast imaging of molecular targets in vivo.

  7. Gd3+-DTPA-bis (N-methylamine) - anionic linear globular Dendrimer-G1; a more efficient MRI contrast media.

    PubMed

    Ghalandarlaki, N; Mohammadi, T D; Agha Babaei, R; Tabasi, M A; Keyhanvar, P; Mehravi, B; Yaghmaei, P; Cohan, R A; Ardestani, M S

    2014-02-01

    By advancing of molecular imaging techniques, magnetic resonance imaging (MRI) is becoming an increasingly important tool in early diagnosis. Researchers have found new ways to increase contrast of MRI images.Therefore some types of drug known as contrast media are produced. Contrast media improve the visibility of internal body structures in MRI images. Gadodiamide (Omniscan®) is one of these contrast media which is produced commercially and used clinically. In this study Gadodiamide was first synthesized and then qualitative and quantitative methods were carried out to ensure the proper synthesis of this drug then to increase the efficiency of this contrast medium use dendrimer that is one kind of nano particle. This dendrimer has a polyethylene glycol (PEG) core and citric acid branches. After dendrimer attached to Gadodiamide to ensure the proper efficient connection between them the stability studies were carried out and cytotoxicity of the drug was evaluated. Finally, after ensuring the non-toxicity of the drug, in vivo studies (injected into mice) MR imaging was performed to examine the impact of synthesis drug on the resolution of image.The result obtained from this study demonstrated that the attachment of Gadodiamide to dendrimer reduces its cytotoxicity and also improved resolution of image. Also the new contrast media (Gd3+-DTPA- bis [N-methylamine] - Dendrimer) - unlike Omniscan® - is biodegradable and able to enter the HEPG2 cell line. The results confirm the hypothesis that using dendrimer to synthesize this new nano contrast medium increases its effectiveness.

  8. The effect of x rays, DTPA, and aspirin on the absorption of plutonium from the gastrointestinal tract of rats

    SciTech Connect

    Sullivan, M.F.; Gorham, L.S.; Miller, B.M.

    1983-04-01

    To measure the effect of radiation on plutonium transport, rats that were exposed to 250-kVp X rays were given /sup 238/Pu 3 days afterwards by either gavage or injection into a ligated segment of the duodenum. In a second group of experiments, rats were either injected intraduodenally with /sup 238/Pu-DTPA or administered the chelate intravenously and the /sup 238/Pu by gavage. In a third experiment, rats that had been gavaged with 200 or 400 mg/kg/day of aspirin for 2 days were injected intragastrically with /sup 238/Pu nitrate. Results of the first experiment showed a dose-dependent increase in /sup 238/Pu absorption between 800 and 1500 rad of lower-body X irradiation. Intravenous or intraduodenal injections of DTPA caused a marked increase in /sup 238/Pu absorption but resulted in decreased plutonium deposition in the skeleton and liver. Retention of /sup 238/Pu in the skeleton of rats given aspirin was double that of controls, but the effect on plutonium absorption was less marked than that of DTPA.

  9. Influence of tyramine-induced neurotoxicity on kinetics of first-pass brain TC-99m-DTPA

    SciTech Connect

    Malveaux, E.; Schmidt, F.; Sarper, R.; Camp, V.; Faraj, B.A.

    1986-03-05

    Tyramine (T) induces coma in phenelzine-treated dogs. The objective of the present investigation was to examine the influence of T in MAO-inhibited dogs on the kinetics of Tc-99m-DTPA during its first passage through the brain by nuclear imaging. The study began with anesthetized dogs (n=10) in a supine position over the camera detector. Data acquisition was started simultaneously following the rapid intracarotid injection of Tc-99m-DTPA (30 mCi) and 60 0.5 second images of the brain were taken. T induced increased uptake with a concomittant impairment in the elimination of Tc-99m-DPTA from the brain of these treated animals as compared to controls. This was accompanied by an appreciable reduction in hemispheric cerebral blood flow (CBF) (56 +/- 19 vs 110 +/- 16 ml/100g/min). Increased cerebrovascular permeability of Tc-99m-DTPA and decreased CBF correlated significantly with development of intracranial hypertension and elevation in CSF catecholamines in these animals. T may have implication in the development of cerebral edema of Reye's syndrome.

  10. The determination of relative renal function in a pediatric population using Tc-99m DTPA and Tc-99m DMSA

    SciTech Connect

    Rosen, P.R.; Kuruc, A.; Treves, S.T.

    1985-05-01

    Three methods for evaluating relative renal function in a pediatric population were compared. The clinical and nuclear medicine data of 73 patients were reviewed. Pertinent data included patient age, serum creatinine and the referral diagnosis (reflux, hypertension, obstructive uropathy). Time activity curves for renal regions of interest (ROI) were obtained by renography with Tc-99m DTPA, and deconvolved by an externally detected blood pool curve Furosemide was then administered to evaluate the renal collecting system (if indicated). This was followed by DMSA administration. Relative function was determined in 3 ways: 1) Accumulated renal DTPA activity 60-120 sec. following injection. 2) Amplitude of the tubular phase of the deconvolved renal curve and, 3) Accumulated Tc-99m DMSA activity in renal ROI 4 or 24 hrs. post-injection. Regression analysis revealed: 1) The basic relationship of relative functional data obtained by all three methods was not affected by creatinine, age or other factors. 2) The relationship between the three methods is linear and highly correlated. 3) The DMSA values may be predicted from either method of analyzing the DTPA study using appropriate predictor equations. The authors conclude that Tc-99m DMSA, due to its higher cost and more radiation exposure should not be used for the routine evaluation of relative renal function.

  11. Detection of renal ischemic lesions using Gd-DTPA enhanced turbo FLASH MRI: Experimental and clinical results

    SciTech Connect

    Vosshenrich, R.; Fischer, U.; Funke, M.; Kopka, L.; Grabbe, E.

    1996-03-01

    Our goal was to investigate the role of Gd-DTPA-enhanced dynamic MRI in the evaluation of renal ischemic lesions. With a turbo FLASH sequence before and after injection of Gd-DTPA, nine foxhound dogs after 60-120 min of renal ischemia underwent MR examination. In addition, five patients with a tumor in a solitary kidney were examined before and after nephron-sparing renal surgery to evaluate renal perfusion and function. The experimental and clinical findings were correlated with conventional measurements of kidney function and with histological findings. Complete renal ischemia leads to a poor corticomedullary differentiation in Gd-DTPA-enhanced turbo FLASH MRI. The signal-intensity-versus-time plots of kidneys with significant postischemic changes show a less steep increase of signal intensity in the cortex and a steeper increase of signal intensity in the medulla than those of normal kidneys. Dynamic MRI demonstrate renal morphology and reflect the functional status of the renal vasculature. 21 refs., 8 figs., 1 tab.

  12. MR Prediction of Liver Function and Pathology Using Gd-EOB-DTPA: Effect of Liver Volume Consideration

    PubMed Central

    Shimamoto, Dai; Nishie, Akihiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Takayama, Yukihisa; Fujita, Nobuhiro; Shirabe, Ken; Hida, Tomoyuki; Kubo, Yuichiro; Honda, Hiroshi

    2015-01-01

    Purpose. To evaluate whether the diagnostic performance of Gd-EOB-DTPA-enhanced MRI in evaluating liver function and pathology is improved by considering liver volume (LV). Methods. This retrospective study included 104 patients who underwent Gd-EOB-DTPA-enhanced MRI before liver surgery. For each patient, using the precontrast and hepatobiliary phase images, we calculated the increase rate of the liver-to-spleen signal intensity ratio (LSR), that is, the “ΔLSR,” and the increase rate of the liver-to-muscle signal intensity ratio (LMR), that is, the “ΔLMR.” ΔLSR × LV and ΔLMR × LV were also calculated. The correlation of each MR parameter with liver function data or liver pathology was assessed. The correlation coefficients were compared between ΔLSR (ΔLMR) and ΔLSR (ΔLMR) × LV. Results. The correlation coefficient between ΔLSR (ΔLMR) × LV and cholinesterase was significantly higher than that between ΔLSR (ΔLMR) and cholinesterase. The correlation coefficient between ΔLSR (ΔLMR) × LV and the degree of fibrosis or necroinflammatory activity was significantly lower than that between ΔLSR (ΔLMR) and the degree of fibrosis or necroinflammatory activity. Conclusion. The inclusion of liver volume may improve Gd-EOB-DTPA-based predictions of liver function, but not in predictions of liver pathology. PMID:26609519

  13. Targeting of diethylene triamine pentaacetic acid encapsulated in liposomes to rat liver: an effective strategy to prevent bone deposition and increase urine elimination of plutonium in rats.

    PubMed

    Phan, G; Ramounet-Le Gall, B; Manceau, J; Fanet, M; Benech, H; Fritsch, P; Fattal, E; Deverre, J R

    2004-06-01

    To modify the distribution of the chelating agent diethylene triamine pentaacetic acid (DTPA) by using a formulation approach with liposomes in order to match the in vivo distribution of plutonium (Pu) and, as a consequence, to improve actinide decorporation. DTPA was encapsulated in conventional and stealth liposomes. Their pharmacokinetics and ability to remove Pu were evaluated in rats 2 and 16 days after a single intravenous treatment given 2 h after contamination with colloidal Pu (239Pu phytate) or with soluble Pu (238Pu citrate). Both formulations induced major pharmacokinetic modifications in rats, allowing an accumulation of [14C]-DTPA mainly in the liver and secondarily (for stealth liposomes) in bone and spleen. These modifications were associated with major increases in urine elimination and with a decrease in skeletal Pu deposition, depending of the nature of the Pu contaminant. After contamination by Pu phytate, conventional liposomes of DTPA (6 micromol kg(-1)) were as efficient as free DTPA (30 micromol kg(-1)) in maintaining the Pu content in the femur below 4.3% of the injected dose after 16 days, a 3.6-fold reduction compared with free DTPA (4 micromol kg(-1)) treatment or without treatment. A formulation approach with liposomes appears to be a powerful tool to improve the efficiency of Pu chelating agents in vivo.

  14. PET imaging of tumor angiogenesis in mice with VEGF-A targeted 86Y-CHX-A″-DTPA-bevacizumab

    PubMed Central

    Nayak, Tapan K.; Garmestani, Kayhan; Baidoo, Kwamena E.; Milenic, Diane E.; Brechbiel, Martin W.

    2010-01-01

    Bevacizumab is a humanized monoclonal antibody that binds to tumor-secreted VEGF-A and inhibits tumor angiogenesis. In 2004, the antibody was approved by the United States FDA for the treatment of metastatic colorectal carcinoma in combination with chemotherapy. This report describes the preclinical evaluation of a radioimmunoconjugate, 86Y-CHX-A″-DTPA-bevacizumab, for potential use in PET imaging of VEGF-A tumor angiogenesis and as a surrogate marker for 90Y based radioimmunotherapy. Bevacizumab was conjugated to CHX-A″-DTPA and radiolabeled with 86Y. In vivo biodistribution and PET imaging studies were performed on mice bearing VEGF-A secreting human colorectal (LS-174T), human ovarian (SKOV-3) and VEGF-A negative human mesothelioma (MSTO-211H) xenografts. Biodistribution and PET imaging studies demonstrated high specific tumor uptake of the radioimmunoconjugate. In mice bearing VEGF-A secreting LS-174T, SKOV-3 and VEGF-A negative MSTO-211H tumors, the tumor uptake at 3 d post-injection (p.i) was 13.6 ± 1.5, 17.4 ± 1.7 and 6.8 ± 0.7 % ID/g, respectively. The corresponding tumor uptake in mice co-injected with 0.05 mg cold bevacizumab were 5.8 ± 1.3, 8.9 ± 1.9 and 7.4 ± 1.0 % ID/g, respectively at the same time point, demonstrating specific blockage of the target in VEGF-A secreting tumors. The LS-174T and SKOV3 tumors were clearly visualized by PET imaging after injecting 1.8–2.0 MBq 86Y-CHX-A″-DTPA-bevacizumab. Organ uptake quantified by PET closely correlated (r2=0.87, p=0.64, n=18) to values determined by biodistribution studies. This preclinical study demonstrates the potential of the radioimmunoconjugate, 86Y-CHX-A″-DTPA-bevacizumab, for non-invasive assessment of the VEGF-A tumor angiogenesis status and as a surrogate marker for 90Y-CHX-A″-DTPA-bevacizumab radioimmunotherapy. PMID:20473899

  15. PET imaging of tumor angiogenesis in mice with VEGF-A-targeted (86)Y-CHX-A″-DTPA-bevacizumab.

    PubMed

    Nayak, Tapan K; Garmestani, Kayhan; Baidoo, Kwamena E; Milenic, Diane E; Brechbiel, Martin W

    2011-02-15

    Bevacizumab is a humanized monoclonal antibody that binds to tumor-secreted vascular endothelial growth factor (VEGF)-A and inhibits tumor angiogenesis. In 2004, the antibody was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal carcinoma in combination with chemotherapy. This report describes the preclinical evaluation of a radioimmunoconjugate, (86)Y-CHX-A″-DTPA-bevacizumab, for potential use in Positron Emission Tomography (PET) imaging of VEGF-A tumor angiogenesis and as a surrogate marker for (90)Y-based radioimmunotherapy. Bevacizumab was conjugated to CHX-A″-DTPA and radiolabeled with (86)Y. In vivo biodistribution and PET imaging studies were performed on mice bearing VEGF-A-secreting human colorectal (LS-174T), human ovarian (SKOV-3) and VEGF-A-negative human mesothelioma (MSTO-211H) xenografts. Biodistribution and PET imaging studies demonstrated highly specific tumor uptake of the radioimmunoconjugate. In mice bearing VEGF-A-secreting LS-174T, SKOV-3 and VEGF-A-negative MSTO-211H tumors, the tumor uptake at 3 days postinjection was 13.6 ± 1.5, 17.4 ± 1.7 and 6.8 ± 0.7 % ID/g, respectively. The corresponding tumor uptake in mice coinjected with 0.05 mg cold bevacizumab were 5.8 ± 1.3, 8.9 ± 1.9 and 7.4 ± 1.0 % ID/g, respectively at the same time point, demonstrating specific blockage of the target in VEGF-A-secreting tumors. The LS-174T and SKOV3 tumors were clearly visualized by PET imaging after injecting 1.8-2.0 MBq (86)Y-CHX-A″-DTPA-bevacizumab. Organ uptake quantified by PET closely correlated (r(2) = 0.87, p = 0.64, n = 18) to values determined by biodistribution studies. This preclinical study demonstrates the potential of the radioimmunoconjugate, (86)Y-CHX-A″-DTPA-bevacizumab, for noninvasive assessment of the VEGF-A tumor angiogenesis status and as a surrogate marker for (90)Y-CHX-A″-DTPA-bevacizumab radioimmunotherapy. Copyright © 2010 UICC.

  16. Tumor-Targeted HPMA Copolymer-(RGDfK)-(CHX-A″-DTPA) Conjugates Show Increased Kidney Accumulation

    PubMed Central

    Borgman, Mark P.; Coleman, Tomika; Kolhatkar, Rohit B.; Geyser-Stoops, Sandra; Line, Bruce R.; Ghandehari, Hamidreza

    2008-01-01

    N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-RGDfK conjugates targeting the αvβ3 integrin have shown increased accumulation in solid tumors and promise for selective delivery of radiotherapeutics to sites of angiogenesis- or tumor-expressed αvβ3 integrin. An unresolved issue in targeting radiotherapeutics to solid tumors is toxicity to non-target organs. To reduce toxicity of radiolabeled conjugates, we have synthesized HPMA copolymer-RGDfK conjugates with varying molecular weight and charge content to help identify a polymeric structure that maximizes tumor accumulation while rapidly clearing from non-targeted organs. Endothelial cell binding studies showed that copolymer conjugates of approximately 43, 20 and 10 kD actively bind to the αvβ3 integrin. Scintigraphic images showed rapid clearance of indium-111 radiolabeled conjugates from the blood pool and high kidney accumulation within 1 h in tumor bearing mice. Biodistribution data confirms images with high accumulation in kidney (max 210% ID/g for 43 kD conjugate) and lower tumor accumulation (max 1.8% ID/g for 43kD conjugate). While actively binding to the αvβ3 integrin in vitro, HPMA copolymer-RGDfK conjugates with increased negative charge through increased CHX-A″-DTPA chelator content in the side chains causes increased kidney accumulation with a loss of tumor binding in vivo. PMID:18687371

  17. Tumor-targeted HPMA copolymer-(RGDfK)-(CHX-A''-DTPA) conjugates show increased kidney accumulation.

    PubMed

    Borgman, Mark P; Coleman, Tomika; Kolhatkar, Rohit B; Geyser-Stoops, Sandra; Line, Bruce R; Ghandehari, Hamidreza

    2008-12-18

    N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-RGDfK conjugates targeting the alpha(v)beta(3) integrin have shown increased accumulation in solid tumors and promise for selective delivery of radiotherapeutics to sites of angiogenesis- or tumor-expressed alpha(v)beta(3) integrin. An unresolved issue in targeting radiotherapeutics to solid tumors is toxicity to non-target organs. To reduce toxicity of radiolabeled conjugates, we have synthesized HPMA copolymer-RGDfK conjugates with varying molecular weight and charge content to help identify a polymeric structure that maximizes tumor accumulation while rapidly clearing from non-targeted organs. Endothelial cell binding studies showed that copolymer conjugates of approximately 43, 20 and 10 kD actively bind to the alpha(v)beta(3) integrin. Scintigraphic images showed rapid clearance of indium-111 ((111)In) radiolabeled conjugates from the blood pool and high kidney accumulation within 1 h in tumor bearing mice. Biodistribution data confirms images with high accumulation in kidney (max 210% ID/g for 43 kD conjugate) and lower tumor accumulation (max 1.8% ID/g for 43 kD conjugate). While actively binding to the alpha(v)beta(3) integrin in vitro, HPMA copolymer-RGDfK conjugates with increased negative charge through increased CHX-A''-DTPA chelator content in the side chains causes increased kidney accumulation with a loss of tumor accumulation in vivo.

  18. The variability of processing of technetium-99m DTPA renography. Role of interpolative background subtraction.

    PubMed

    Hurwitz, G A; Champagne, C L; Gravelle, D R; Smith, F J; Powe, J E

    1993-04-01

    In quantitative renography, observer-dependent selection of renal outlines and background regions may account for considerable variability. This study of differential renal function with Tc-99m DTPA scintigraphy compares interpolative background subtraction with the authors' routine techniques; the latter involves background-subtracted uptake on data integrated over 1-3 minutes after injection. Other techniques considered were omission of background subtraction and use of 1-2 minute integration. The normal range was established in 24 hypertensive patients who had a normal angiogram and a normal radiometric glomerular filtration rate. The test set of 52 other hypertensive patients included 27 with renal artery stenosis. All techniques correlated well with the routine method (r > or = 0.98); however the interpolative background technique was unique in preserving the depiction of renal asymmetry but reducing the variability of replicate measurements (P < 0.05). Reduced renal function increased the variability of routine measurements, but the interpolative background subtraction method performed better in this instance (P < 0.01). Thus, the new technique appears to improve the definition of renal outlines and increase the reliability of measurements of differential renal function.

  19. Microcirculation of the fingers in Raynaud's syndrome: (99m)Tc-DTPA imaging.

    PubMed

    Csiki, Z; Garai, I; Varga, J; Szücs, G; Galajda, Z; András, C; Zeher, M; Galuska, L

    2005-02-01

    We investigated the circulatory characteristics of patients suffering of primary and secondary Raynaud's syndrome. We examined 106 patients presenting with the classical symptoms of Raynaud's syndrom (47 primary, 59 secondary) by hand perfusion scintigraphy developed by our Department of Nuclear Medicine. After visual evaluation we analyzed the images semiquantitatively, using the finger to palm ratio. We statistically compared the patients with primary and those with secondary Raynaud's syndrome. By visual evaluation we constated regional perfusion disturbances in 42 from 59 patients with secondary Raynaud's syndrome. However, this was observed in only 3 from 47 patients with the primary form of this disease. This difference was statistically significant (p<0.001). Semiquantitative analysis showed that the finger/palm ratios (FPR) were significantly lower (p<0.05) for the patients with primary Raynaud's syndrome. No differences in the FPR values concerning sex or right and left side. The hand perfusion scintigraphy with (99m)Tc-DTPA is a noninvasive, cost effective diagnostic tool, which objectively reflects the global and regional microcirculatory abnormalities of the hands, and provides quantitative data for follow-up.

  20. Retention and distribution of two 99mTc-DTPA labelled vaginal dosage forms.

    PubMed

    Chatterton, Barry E; Penglis, Stan; Kovacs, Julie C; Presnell, Bernardine; Hunt, Barry

    2004-03-01

    To objectively evaluate the performance of new vaginal dosage forms, it is important to determine their time of residence and their distribution. This paper describes the in vivo characteristics of a reference and test product in this situation. A randomised cross-over study was performed in the same phase of the menstrual cycle in eight pre-menopausal women. The retention and distribution of a commercially available vaginal clotrimazole cream and a test gel product, each "labelled" with 99mTc-DTPA was assessed by gamma scintigraphy for 24 h after administration of the products. Mass balance analysis was attempted by collecting and counting sanitary napkins worn for the study time. Within individuals there was little variation in the clearance of the formulations, but wide variation between individuals with a range between 81 and 1% of the administered doses retained by 24 h. The losses appeared to occur mainly at times of urination with 12 +/- 8% (cream) and 20 +/- 23% (gel) collected on the sanitary napkins, but 46 +/- 34% (cream) and 38 +/- 22% gel activity not accounted for by 24 h. The intravaginal distribution of activity was similar for each product. Radioactive tracer methods are useful in assessing and comparing vaginal dosage forms.

  1. [Dixon's technic for fat suppression. Its potential applications in combination with gadolinium-DTPA].

    PubMed

    Mascalchi, M; Battolla, L; Zampa, V; Falaschi, F; Caramella, D; Bartolozzi, C

    1994-01-01

    Modification of the Dixon technique enables the reconstruction of water and fat images operating at midfield strength. The technique was combined with intravenous administration of gadolinium-DTPA in five patients with lumbosacral spine conditions, four patients with soft tissue neoplasms and three with skeletal neoplasms; all patients were examined at 0.5 T. Mean attenuation of fat signal in T1-weighted images was 85% and implied a redistribution of the gray-scale dynamic range. This allowed easier appreciation of normal and abnormal enhancement in both areas containing fat tissue and areas without it. This was useful in the evaluation of fresh scars in two patients recently submitted to lamino-discectomy and of the prevertebral extension of the inflammatory process in one patient with spondylodiscitis. In the patients with soft tissue neoplasms the combination of fat suppression and Gadolinium was helpful to assess lesion size. Finally, in the patients with skeletal neoplasms fat-suppressed images obviated for the lesion disappearance observed on conventional T1-weighted SE images after contrast administration. The combination of intravenous administration of gadolinium-DPTA with Dixon's fat-suppression technique is a new promising capability of midfield MRI.

  2. Case Study: Three Acute 241Am Inhalation Exposures with DTPA Therapy

    SciTech Connect

    Carbaugh, Eugene H.; Lynch, Timothy P.; Cannon, Curt; Lewis, Loren L.

    2010-10-01

    Three workers incurred inhalation exposures to 241Am oxide as a result of waste sorting and compaction activities. The magnitudes of the exposures were not fully recognized until the following day when an in vivo chest count identified a significant lung deposition of 241Am in a male worker, and DTPA chelation therapy was initiated. Two additional workers (one female and one male) were then identified as sufficiently exposed to also warrant therapy. In vivo bioassay measurements were performed over the ensuing 6 months to quantify the 241Am activity in the lungs, liver, and skeleton. Urine and fecal samples were collected and showed readily detectable 241Am. Clinical lab tests and medical evaluations all showed normal results. There were no significant adverse clinical health effects from the therapy. The estimated 241Am inhalation intakes for the three workers were 1800 Bq, 630 Bq, and 150 Bq. Lung retention showed somewhat longer pulmonary clearance half-times than standard inhalation class W or absorption Type M assumptions. The three underwent slightly different therapy regimes, with therapy effectiveness factors (defined as the ratio of the reference doses without therapy relative to the final assessed doses) of 4.65, 1.93, and 1.67, respectively.

  3. Assessment of tumor angiogenesis: dynamic contrast-enhanced MRI with paramagnetic nanoparticles compared with Gd-DTPA in a rabbit Vx-2 tumor model.

    PubMed

    Kassner, Andrea; Thornhill, Rebecca E; Liu, Fang; Winter, Patrick M; Caruthers, Shelton D; Wickline, Samuel A; Lanza, Gregory M

    2010-01-01

    The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd-DTPA) using dynamic contrast-enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12-14 days after Vx-2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd-DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (K(i)) maps were calculated using a two-compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The K(i) values estimated using PNs were significantly lower than those obtained for Gd-DTPA (p = 0.018). When PNs and Gd-DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd-DTPA data (p = 0.34). The mean K(i) for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd-DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd-DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis.

  4. Treatment of peritoneal carcinomatosis by targeted delivery of the radio-labeled tumor homing peptide bi-DTPA-[F3]2 into the nucleus of tumor cells.

    PubMed

    Drecoll, Enken; Gaertner, Florian C; Miederer, Matthias; Blechert, Birgit; Vallon, Mario; Müller, Jan M; Alke, Andrea; Seidl, Christof; Bruchertseifer, Frank; Morgenstern, Alfred; Senekowitsch-Schmidtke, Reingard; Essler, Markus

    2009-05-27

    Alpha-particle emitting isotopes are effective novel tools in cancer therapy, but targeted delivery into tumors is a prerequisite of their application to avoid toxic side effects. Peritoneal carcinomatosis is a widespread dissemination of tumors throughout the peritoneal cavity. As peritoneal carcinomatosis is fatal in most cases, novel therapies are needed. F3 is a tumor homing peptide which is internalized into the nucleus of tumor cells upon binding to nucleolin on the cell surface. Therefore, F3 may be an appropriate carrier for alpha-particle emitting isotopes facilitating selective tumor therapies. A dimer of the vascular tumor homing peptide F3 was chemically coupled to the alpha-emitter (213)Bi ((213)Bi-DTPA-[F3](2)). We found (213)Bi-DTPA-[F3](2) to accumulate in the nucleus of tumor cells in vitro and in intraperitoneally growing tumors in vivo. To study the anti-tumor activity of (213)Bi-DTPA-[F3](2) we treated mice bearing intraperitoneally growing xenograft tumors with (213)Bi-DTPA-[F3](2). In a tumor prevention study between the days 4-14 after inoculation of tumor cells 6x1.85 MBq (50 microCi) of (213)Bi-DTPA-[F3](2) were injected. In a tumor reduction study between the days 16-26 after inoculation of tumor cells 6x1.85 MBq of (213)Bi-DTPA-[F3](2) were injected. The survival time of the animals was increased from 51 to 93.5 days in the prevention study and from 57 days to 78 days in the tumor reduction study. No toxicity of the treatment was observed. In bio-distribution studies we found (213)Bi-DTPA-[F3](2) to accumulate in tumors but only low activities were found in control organs except for the kidneys, where (213)Bi-DTPA-[F3](2) is found due to renal excretion. In conclusion we report that (213)Bi-DTPA-[F3](2) is a novel tool for the targeted delivery of alpha-emitters into the nucleus of tumor cells that effectively controls peritoneal carcinomatosis in preclinical models and may also be useful in oncology.

  5. Transmetallation of Gd-DTPA by Fe3+, Cu2+ and Zn2+ in water: batch experiments and coagulation-flocculation simulations.

    PubMed

    Rabiet, Marion; Letouzet, Marine; Hassanzadeh, Sepideh; Simon, Stéphane

    2014-01-01

    The study investigates the stability of gadolinium-DTPA complex in presence of competing metallic ions, Fe(3+), Cu(2+) and Zn(2+) using batch experiments and coagulation-flocculation simulations. High performance liquid chromatography with fluorescence detection was used for simultaneous analysis of chelate gadolinium (Gd-DTPA) and free Gd(III) ion in water. It was shown that Cu(2+) has a strong affinity for DTPA and could lead to a complete release of Gd(3+). Fe(3+) appeared also to compete strongly with Gd(3+) for DTPA binding since up to 80% of Gd-complex was dissociated under iron excess condition. Finally, zinc had a lower influence on Gd speciation: only 15% of Gd(3+) was released with addition of a 5-fold excess of Zn(2+). During coagulation-flocculation simulation, Fe(3+) was able to displace about 27% of Gd-DTPA, and no adsorption was observed onto flocs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. The DyP-type peroxidase DtpA is a Tat-substrate required for GlxA maturation and morphogenesis in Streptomyces

    PubMed Central

    Petrus, Marloes L. C.; Chaplin, Amanda K.; Worrall, Jonathan A. R.; van Wezel, Gilles P.

    2016-01-01

    The filamentous bacterium Streptomyces lividans depends on the radical copper oxidase GlxA for the formation of reproductive aerial structures and, in liquid environments, for the formation of pellets. Incorporation of copper into the active site is essential for the formation of a cross-linked tyrosyl-cysteine cofactor, which is needed for enzymatic activity. In this study, we show a crucial link between GlxA maturation and a group of copper-related proteins including the chaperone Sco and a novel DyP-type peroxidase hereinafter called DtpA. Under copper-limiting conditions, the sco and dtpA deletion mutants are blocked in aerial growth and pellet formation, similarly to a glxA mutant. Western blot analysis showed that GlxA maturation is perturbed in the sco and dtpA mutants, but both maturation and morphology can by rescued by increasing the bioavailability of copper. DtpA acts as a peroxidase in the presence of GlxA and is a substrate for the twin-arginine translocation (Tat) translocation pathway. In agreement, the maturation status of GlxA is also perturbed in tat mutants, which can be compensated for by the addition of copper, thereby partially restoring their morphological defects. Our data support a model wherein a copper-trafficking pathway and Tat-dependent secretion of DtpA link to the GlxA-dependent morphogenesis pathway. PMID:26740586

  7. Renal uptakes of 99mTc-MAG3, 99mTc-DTPA, and 99mTc-DMSA in rabbits with unilateral ureteral obstruction.

    PubMed

    Lee, Won Guk; Kim, Joong-Hyun; Kim, Jong Min; Shim, Kyung Mi; Kang, Seong Soo; Chae, Hong In; Choi, Seok Hwa

    2010-01-01

    Renal function measurements using (99m)Tc-DTPA and (99m)Tc-MAG(3) dynamic scintigraphs were compared to those obtained using (99m)Tc-DMSA static scintigraphy. Eighteen experimental rabbits were randomly divided into (99m)Tc-DTPA-, (99m)Tc-MAG(3)-, and (99m) Tc-DMSA-injected groups. Experimental unilateral renal damage was induced by ligating a unilateral right ureter in 18 rabbits. Scintigraphic images were obtained at 2 and 5 h after intravenous injection of (99m)Tc-DMSA, or immediately after administration of (99m)Tc-DTPA or (99m)Tc-MAG(3). For the dynamic images using (99m)Tc-DTPA and (99m)Tc-MAG(3), rapid sequential images were obtained every 2 s for 30 images up to 1 min. The three groups presented different relative renal functions between the left normal and the right abnormal kidneys at 1, 2, 3, and 4 weeks post-ligation (p<0.05). However, the between-group comparisons showed no significant differences at any time. These results suggest that dynamic images of (99m)Tc-DTPA and (99m)Tc-MAG(3) can be used to measure the relative renal function in place of the static image of (99m)Tc-DMSA.

  8. Real-time tracking of dissociation of hyperpolarized 89Y-DTPA: a model for degradation of open-chain Gd3+ MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Ferguson, Sarah; Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Kovacs, Zoltan; Lumata, Lloyd

    Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the 89Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T1 relaxation time of 89Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized 89Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd3+ MRI contrast agents will be discussed. This work was supported by the U.S. Department of Defense Award Number W81XWH-14-1-0048 and by the Robert A. Welch Foundation research Grant Number AT-1877.

  9. Effect of Zn-DTPA therapy on the maternal transfer of /sup 241/Am or /sup 237/Pu to young mice

    SciTech Connect

    Lloyd, R.D.; Jones, C.W.; Mays, C.W.; Brammer, T.W.; Burnham, J.W.

    1985-09-01

    Newborn mice exposed to /sup 241/Am or /sup 237/Pu during gestation and whose mothers were given Zn-DTPA at various times before parturition contained less radioactivity than comparable newborn mice given identical /sup 241/Am or /sup 237/Pu exposure without Zn-DTPA treatment of the mothers. There was no net increase in radionuclide transfer from mothers to unborn young as a result of maternal administration of Zn-DTPA, regardless of the pregnancy stage during which the radioactivity and decorporation treatments were given. Administration of /sup 241/Am followed after three days by extended Zn-DTPA therapy resulted in lower fetal content of radioactivity in litters conceived long after or soon after maternal exposure to /sup 241/Am. These data indicate that the risk from Am and Pu to unborn young can be reduced by Zn-DTPA treatment of the pregnant mother and of the female who becomes pregnant subsequently. This information may prove to be of significance with the increasing probability of Am or Pu exposure to women in the nuclear industry who could be pregnant at the time or who may conceive a child in the future.

  10. Single-sample methods to measure GFR with technetium-99m-DTPA.

    PubMed

    Li, Y; Lee, H B; Blaufox, M D

    1997-08-01

    Many single-sample methods have been suggested to simplify the methodology of glomerular filtration rate (GFR) measurement. The relative accuracy of these competing methods is still not clear for clinical practice. Fifty-four GFR studies with 99mTc-DTPA were performed on 37 adult patients (serum creatinine 0.8-10 mg/dl). Each study included a UV/P, plasma clearance method (three-sample) and single-sample methods. The single-sample methods used were those of Christensen and Groth (modified by Watson), Constable, Dakubu, Groth and Aasted, Jacobsson, Morgan, Russell and Tauxe. When the GFR > or = 30 ml/min (n = 26), all of the single-sample methods were highly correlated with UV/P. The correlation of the single-sample method with the plasma clearance was higher than with UV/P. In this group (GFR > or = 30 ml/min), the Groth 4-hr sample method had the best value of both absolute difference and percent absolute difference (mean +/- s.e. = 11.05 +/- 2.51 ml/min and 14.08% +/- 2.43%, respectively). Most single-sample methods do not perform well at GFR < 30 ml/min (n = 28), and none of them has a good correlation with UV/P or plasma clearance at this level of renal function. However, the Groth and Aasted's 4-hr sample method was the best compared with others (mean +/- s.e. = 8.43 +/- 1.30 ml/min for absolute difference, and 65.91% +/- 16.70% for percent absolute difference). Single-sample methods may not correctly predict GFR in advanced renal failure. Groth and Aasted's method with 4-hr plasma sample has both the lowest mean absolute difference and percent absolute difference in both the group with GFR > or = 30 ml/min and GFR < 30 ml/min. All methods perform acceptably at GFR > or = 30 ml/min.

  11. Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants

    PubMed Central

    Lalwani, Sanjay K.; Agarkhedkar, Sharad; Sundaram, Balasubramanian; Mahantashetti, Niranjana S.; Malshe, Nandini; Agarkhedkar, Shalaka; Van Der Meeren, Olivier; Mehta, Shailesh; Karkada, Naveen; Han, Htay Htay; Mesaros, Narcisa

    2017-01-01

    ABSTRACT Multivalent combination vaccines have reduced the number of injections and therefore improved vaccine acceptance, timeliness of administration and global coverage. The hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib; Infanrix hexa™) vaccine, administered according to various schedules, is widely used for the primary vaccination of infants worldwide. In the current publication, we are presenting the immunogenicity and safety of 3 doses of DTPa-HBV-IPV/Hib vaccine when administered to Indian infants. 224 healthy infants (mean age 6.8 weeks) were vaccinated at 6–10–14 weeks (W) of age (n = 112) or 2–4–6 months (M) of age (n = 112). One month after the third vaccine dose, the seroprotection/seropositivity status against diphtheria, pertussis, tetanus, polio, hepatitis B and Hib antigens ranged from 98.6% to 100% in both groups. The vaccine response rate to the pertussis antigens ranged from 97% to 100%. Pain (6–10–14W group: 25.2%; 2–4–6M group: 13.4%) and fever (15.3% and; 15.2%, respectively) were the most frequently reported solicited local and general symptoms. Unsolicited adverse events were reported for 35.7% (6–10–14W group) and 22.3% (2–4–6M group) of subjects. No vaccine related serious adverse events were reported. In conclusion, the hexavalent DTPa-HBV-IPV/Hib vaccine was immunogenic and well tolerated, irrespective of the dosing schedule. PMID:27629913

  12. Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants.

    PubMed

    Lalwani, Sanjay K; Agarkhedkar, Sharad; Sundaram, Balasubramanian; Mahantashetti, Niranjana S; Malshe, Nandini; Agarkhedkar, Shalaka; Van Der Meeren, Olivier; Mehta, Shailesh; Karkada, Naveen; Han, Htay Htay; Mesaros, Narcisa

    2017-01-02

    Multivalent combination vaccines have reduced the number of injections and therefore improved vaccine acceptance, timeliness of administration and global coverage. The hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib; Infanrix hexa™) vaccine, administered according to various schedules, is widely used for the primary vaccination of infants worldwide. In the current publication, we are presenting the immunogenicity and safety of 3 doses of DTPa-HBV-IPV/Hib vaccine when administered to Indian infants. 224 healthy infants (mean age 6.8 weeks) were vaccinated at 6-10-14 weeks (W) of age (n = 112) or 2-4-6 months (M) of age (n = 112). One month after the third vaccine dose, the seroprotection/seropositivity status against diphtheria, pertussis, tetanus, polio, hepatitis B and Hib antigens ranged from 98.6% to 100% in both groups. The vaccine response rate to the pertussis antigens ranged from 97% to 100%. Pain (6-10-14W group: 25.2%; 2-4-6M group: 13.4%) and fever (15.3% and; 15.2%, respectively) were the most frequently reported solicited local and general symptoms. Unsolicited adverse events were reported for 35.7% (6-10-14W group) and 22.3% (2-4-6M group) of subjects. No vaccine related serious adverse events were reported. In conclusion, the hexavalent DTPa-HBV-IPV/Hib vaccine was immunogenic and well tolerated, irrespective of the dosing schedule.

  13. Labeling anti-HER2/neu monoclonal antibodies with 111In and 90Y using a bifunctional DTPA chelating agent.

    PubMed

    Blend, Michael J; Stastny, Jerry J; Swanson, Steven M; Brechbiel, Martin W

    2003-06-01

    The goal of this investigation was to develop stable radioimmunoconjugates (RICs) of anti-HER2/neu monoclonal antibodies (MoAbs) for imaging and therapy in an animal model bearing human breast tumor xenografts that express normal (MCF-7 cells) and increased amounts of HER2/neu receptors (HCC-1954, BT-474, SKBR-3 cells) on their cell surface membranes. Pharmacy-grade Herceptin, a murine anti-HER2/neu MoAb, and nonspecific mouse IgG protein were conjugated with the recently developed DTPA linker known as CHX-A"-DTPA. These immunoconjugates were labeled with (111)InCl(3) and (90)YCl(3). Using a molar excess of 10:1 CHX-A"-DTPA to immunoglobulin, average specific activities of 1.87 microCi (111)In/microg RIC and 2.71 microCi (90)Y/microg RIC were obtained. The purity of RICs was 96%+ for (111)In and 99%+ for (90)Y. Stability in human plasma at 37 degrees C for both RICs ranged from 98% at 24 h to 85% at 96 h. Binding capacity of the RICs was tested with human cancer cell lines MCF-7, HCC-1954, BT-474, and SKBR-3. Using (111)In-labeled nonspecific IgG protein as a control, (111)In-Herceptin RIC was found to bind to MCF-7 cells with a ratio of 2.5:1 and to SKBR-3 cells with a ratio of 85:1 after 3 h of incubation. (111)In anti-HER2/neu RIC bound to MCF-7 cells with a ratio of 6:1 and to SKBR-3 cells with a ratio of 115:1 after 3 h of incubation. (90)Y-anti-HER2/neu RIC bound 10-times greater to BT-474 cells than to MCF-7 cells. Thus, these MoAbs can be labeled with (111)In and (90)Y using the CHX-A"-DTPA linker. The resulting RICs ((111)In- and (90)Y-anti HER2/neu antibodies) are stable and bind significantly to HER2 overexpressing tumor cell lines.

  14. A feasibility study evaluating the relationship between dose and focal liver reaction in stereotactic ablative radiotherapy for liver cancer based on intensity change of Gd-EOB-DTPA-enhanced magnetic resonance images

    PubMed Central

    Jung, Sang Hoon; Yu, Jeong Il; Lim, Do Hoon; Han, Youngyih

    2016-01-01

    Purpose In order to evaluate the relationship between the dose to the liver parenchyma and focal liver reaction (FLR) after stereotactic ablative body radiotherapy (SABR), we suggest a novel method using a three-dimensional dose distribution and change in signal intensity of gadoxetate disodium-gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) hepatobiliary phase images. Materials and Methods In our method, change of the signal intensity between the pretreatment and follow-up hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI was calculated and then threshold dose (TD) for developing FLR was obtained from correlation of dose with the change of the signal intensity. For validation of the method, TDs for six patients, who had been treated for liver cancer with SABR with 45–60 Gy in 3 fractions, were calculated using the method, and we evaluated concordance between volume enclosed by isodose of TD by the method and volume identified as FLR by a physician. Results The dose to normal liver was correlated with change in signal intensity between pretreatment and follow-up MRI with a median R2 of 0.935 (range, 0.748 to 0.985). The median TD by the method was 23.5 Gy (range, 18.3 to 39.4 Gy). The median value of concordance was 84.5% (range, 44.7% to 95.9%). Conclusion Our method is capable of providing a quantitative evaluation of the relationship between dose and intensity changes on follow-up MRI, as well as determining individual TD for developing FLR. We expect our method to provide better information about the individual relationship between dose and FLR in radiotherapy for liver cancer. PMID:27104169

  15. In vivo examination of 111In-bis-5HT-DTPA to target myeloperoxidase in atherosclerotic ApoE knockout mice.

    PubMed

    Wu, Ming-Che; Ho, Hsin-I; Lee, Te-Wei; Wu, Hua-Lin; Lo, Jem-Mau

    2012-08-01

    The aim of the study is to assess the feasibility of imaging specific activity of myeloperoxidase (MPO), a leukocyte-derived enzyme with important role in atherosclerosis, by SPECT/CT using a novel radiotracer, (111)In-bis-5-hydroxytryptamide-diethylenetriamine-pentaacetate ((111)In-bis-5HT-DTPA). Bis-5HT-DTPA was synthesized. Oligomerization of bis-5HT-DTPA in the presence of MPO/H(2)O(2) was studied and confirmed using MALDI-TOF. Apolipoprotein E knockout (ApoE KO) mice was used as an atherosclerosis-prone rodent model. Biodistribution assay and micro SPECT/CT imaging were carried out to prove the atherosclerosis targeting of (111)In-bis-5HT-DTPA in the ApoE KO mice. MALDI-TOF spectrum showed that the 5HT base agent can self oligomerize after activating by MPO. From the biodistribution study, (111)In-bis-5HT-DTPA was quantified to be retained markedly higher while eliminated much slower in the aortas of the ApoE KO mice than that of the wild type (WT) mice within 1 h post-injection. The nuclear imaging showed significantly higher uptake in the aorta of the ApoE KO mice than that of the WT mice at least within 2 h post-injection. This study described the pharmacokinetics and biodistribution of (111)In-bis-5HT-DTPA in ApoE KO mice and validated its utilization for early detection of atherosclerotic marker, MPO, in the aortic wall of atherosclerosis-prone rodent model.

  16. Synthesis and complexation properties of DTPA-N,N''-bis[bis(n-butyl)]-N'-methyl-tris(amide). Kinetic stability and water exchange of its Gd3+ complex.

    PubMed

    Jaszberényi, Z; Tóth, E; Kálai, T; Király, R; Burai, L; Brücher, E; Merbach, A E; Hideg, K

    2005-02-21

    A novel DTPA-tris(amide) derivative ligand, DTPA-N,N''-bis[bis(n-butyl)]-N'-methyl-tris(amide)(H2L3) was synthesized. With Gd3+, it forms a positively charged [Gd(L3)]+ complex, whereas with Cu2+ and Zn2+ [ML3], [MHL3]+ and [M2L3]2+ species are formed. The protonation constants of H2L3 and the stability constants of the complexes were determined by pH potentiometry. The stability constants are lower than those for DTPA-N,N''-bis[bis(n-butyl)amide)](H3L2), due to the lower negative charge and reduced basicity of the amine nitrogens in (L3)2-. The kinetic stability of [Gd(L3)]+ was characterised by the rates of metal exchange reactions with Eu3+, Cu2+ and Zn2+. The exchange reactions, which occur via proton and metal ion assisted dissociation of [Gd(L3)]+, are significantly slower than for [Gd(DTPA)]2-, since the amide groups cannot be protonated and interact only weakly with the attacking metal ions. The relaxivities of [Gd(L2)] and [Gd(L3)]+ are constant between 10-20 degrees C, indicating a relatively slow water exchange. Above 25 degrees C, the relaxivities decrease, similarly to other Gd3+ DTPA-bis(amide) complexes. The pH dependence of the relaxivities for [Gd(L3)]+ shows a minimum at pH approximately 9, thus differs from the behaviour of Gd3+-DTPA-bis(amides) which have constant relaxivities at pH 3-8 and an increase below and above. The water exchange rates for [Gd(L2)(H2O)] and [Gd(L3)(H2O)]+, determined from a variable temperature (17)O NMR study, are lower than that for [Gd(DTPA)(H2O)]2-. This is a consequence of the lower negative charge and decreased steric crowding at the water binding site in amides as compared to carboxylate analogues. Substitution of the third acetate of DTPA5- with an amide, however, results in a less pronounced decrease in kex than substitution of the first two acetates. The activation volumes derived from a variable pressure (17)O NMR study prove a dissociative interchange and a limiting dissociative mechanism for [Gd(L2)(H2O

  17. Trastuzumab labeled to high specific activity with ¹¹¹In by conjugation to G4 PAMAM dendrimers derivatized with multiple DTPA chelators exhibits increased cytotoxic potency on HER2-positive breast cancer cells.

    PubMed

    Chan, Conrad; Cai, Zhongli; Reilly, Raymond M

    2013-08-01

    To conjugate trastuzumab with/without NLS peptides to G4 PAMAM dendrimers derivatized with DTPA and determine the specific radioactivity (SA) for (111)In labeling, HER2 immunoreactivity and cytotoxicity on breast cancer (BC) cells. G4 dendrimers were reacted with DTPA then conjugated through a thiol to maleimide-derivatized trastuzumab. The SA achievable was determined by incubating 2 to 20 μg with 60 MBq of (111)In. HER2 immunoreactivity, internalization and nuclear importation were measured. The effect of (111)In-DTPA-G4-trastuzumab (5.9 MBq/μg) on the clonogenic survival (CS) of SK-Br-3 or MDA-MB-231 cells with high or low HER2 density, respectively was compared to (111)In-DTPA-NLS-trastuzumab (0.5 MBq/μg). DNA double-strand breaks (DSBs) were measured. DTPA-G4-trastuzumab was labeled with (111)In to a SA (23.6 MBq/μg) which was 100-fold higher than (111)In-DTPA-NLS-trastuzumab. (111)In-DTPA-G4-trastuzumab and (111)In-DTPA-G4-NLS-trastuzumab retained HER2 immunoreactivity and were internalized and imported into the nucleus of BC cells. G4-radioimmunoconjugates were 2-4 fold and 9-fold more cytotoxic to SK-Br-3 and MDA-MB-231 cells, respectively than (111)In-DTPA-NLS-trastuzumab which was associated with an increase in DNA DSBs. Conjugation of trastuzumab to G4 PAMAM dendrimers modified with 30 DTPA permitted high SA (111)In labeling which increased their cytotoxic potency for BC cells with high or low HER2 density.

  18. Bronchoalveolar lavage and clearance of 99m-Tc-DTPA in asbestos workers without evidence of asbestosis.

    PubMed

    Gellert, A R; Langford, J A; Uthayakumar, S; Rudd, R M

    1985-07-01

    We performed BAL and measured the clearance of 99m-Tc-DTPA in 20 non-smoking subjects (mean age 50, range 36-68 years) occupationally exposed to asbestos (mean duration 14, range 3-30 years). All had normal lung function and none had clinical or radiological evidence of asbestosis. The mean BAL results were: total cells per ml 737 X 10(3) (360-1210), percentage macrophages 79 (49-96), percentage lymphocytes 13 (1-42), percentage neutrophils 8 (1-40), percentage eosinophils 0 (0-3), asbestos bodies per ml 83 (0-550). Eight subjects showed increased percentage of lymphocytes and four others showed increased percentages of neutrophils when compared with normal ranges in our laboratory. Higher percentages of neutrophils correlated with longer duration of exposure to asbestos (r = 0.54, P less than 0.025), and shorter time since last exposure to asbestos (r = -0.54, P less than 0.025). Four subjects showed faster clearance of 99m-Tc-DTPA than was observed in 31 normal non-smoking control subjects. There was a tendency for faster solute clearance to be associated with greater numbers of BAL macrophages (r = -0.39, P less than 0.10) but there were no significant relationships between solute clearance and other BAL variables. BAL profiles in asbestos workers may be abnormal in the absence of clinical or radiological evidence of asbestosis.

  19. Limitations of GD-EOB-DTPA-enhanced MRI: can clinical parameters predict suboptimal hepatobiliary phase?

    PubMed

    Kobi, M; Paroder, V; Flusberg, M; Rozenblit, A M; Chernyak, V

    2017-01-01

    To establish cut-off levels of the clinical parameters, which would predict suboptimal 30 minutes delayed hepatobiliary phase (HBP) with high specificity. This retrospective study included patients with chronic liver disease who underwent hepatocellular carcinoma screening with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) between 1 January 2011 and 30 November 2014. For each case, HBP was graded as adequate or suboptimal, based on Liver Image Reporting and Data System (LI-RADS) criteria. The following laboratory data obtained within 3 months of the MRI date was extracted: total bilirubin (TB), direct bilirubin (DB), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALP), albumin, activated partial thromboplastin time (aPTT), and International normalised ratio (INR). Model For End-Stage Liver Disease (MELD) scores were calculated as 3.78×ln[TB] + 11.2×ln[INR] + 9.57×ln[creatinine] + 6.43. Receiver operating characteristic (ROC) curve analysis was used to establish cut-off values for predicting suboptimal HBP. Of 284 patients, 242 (85.2%) patients (91; 57.6% male) had an adequate HBP and 42 (14.8%) patients (13; 61.9% male) had suboptimal HBP, with mean ages of 58.5±9.7 years and 55±12.7 years, respectively (p=0.096). Areas under the ROC curve for predicting suboptimal HBP were 0.85 (95%CI 0.79-0.91) for the MELD score, 0.88 (95%CI 0.82-0.93) for TB, and 0.91 (95%CI 0.86-0.95) for DB. Accuracy, positive likelihood ratios and cut-off values for predicting suboptimal HBP were, respectively: 86.7% and 11.2 for the MELD score ≥16.7, 88.2% and 28.7 for TB ≥4.3 mg/dl, and 91.1% and 36.4 for DB ≥1.3 mg/dl. SGOT, SGPT, and ALP were not statistically significantly different between the groups. Cut-off levels of MELD score, DB, and TB can predict an suboptimal HBP with high accuracy. Prospective identification of patients with a high likelihood of an suboptimal HBP can help to avoid

  20. Highly stabilized gadolinium chelates functionalized on metal nanoparticles as magnetic resonance imaging contrast agent

    NASA Astrophysics Data System (ADS)

    Siddiqui, Talha S.

    Magnetic resonance imaging (MRI) is a non-invasive method for imaging and diagnosing tissue damage, organ function and the vascular system. Magnevist(TM) a complex of diethylenetriaminepentaacetic acid (DTPA) and Gd3+ is a clinically approved contrast agent for MRI. A derivative of DTPA was formed by the addition of two cysteine groups (DTPA-L-Cys) through amide linkage. The Gd complex of this ligand bonds with the silver surfaces through the cysteine thiols. GdDTPA-L-Cys was bound to ˜10nm diameter Ag nanoparticles for use as a multifunctional MRI contrast agent. The ligand and complex were characterized by 1H and 13C NMR, ESI-MS and IR spectroscopy. The silver construct was characterized by TEM, TGA and UV-Vis absorption spectra. The per metal complex r1 relaxivity of GdDTPA-L-Cys{Ag} greater than that of Magnavist(TM) with the same molarity for both compounds. The synthesis of a DTPA derivative is described that allows it to bind to silver or gold nanoparticles through a single thiol linkage (DTPASH). The resulting Gd complex, GdDTPASH, was bound to Ag nanoparticles to create a single monolayer on the surface. The construct was further stabilized in buffered solution with the addition of a thiolated PEG chain. The highly stabilized nanoparticle construct delivers a high payload of Gd compelex and is an effective T1 brightening agent. The production of this type of construct opens the way for engineered multimodal MRI contrast agents.

  1. Bioreducible polyethylenimine nanoparticles for the efficient delivery of nucleic acids.

    PubMed

    Bansal, Ruby; Tayal, Shweta; Gupta, K C; Kumar, Pradeep

    2015-03-14

    Recently, non-viral vectors for nucleic acid delivery have received considerable attention. Among the various non-viral vectors, branched polyethylenimine (bPEI, 25 kDa) has been one of the most widely used carrier systems due to its high transfection efficiency, however, it imparts high cytotoxicity. In this study, we have crosslinked bPEI with a bioreducible linker, 3,3'-dithiodipropionic acid (DTPA), via electrostatic interactions to obtain DTPA crosslinked bPEI (DP) nanoparticles. The crosslinking significantly reduced the cytotoxicity of the nanoparticles. To arrive at the best formulation in terms of nucleic acid transfection, a series of DP nanoparticles were prepared by varying the percentage of crosslinking. The dual action of DTPA, i.e. partial blocking of the charge density as well as crosslinking to convert bPEI into its nanoparticles, did not alter the pDNA condensation ability of the so-formed nanoparticles, rather the strategy favoured the unpackaging of the complexes inside the cells improving the release of pDNA, which resulted in a higher transfection efficiency. All the formulations carried nucleic acids inside the cells and exhibited significantly higher transfection efficiencies than native bPEI and the commercial transfection reagent, Lipofectamine™. Sequential siRNA delivery displayed significant suppression in the target gene expression. All together, the evaluation of the delivery systems demonstrates that the newly synthesized DP NPs are quite promising as non-viral gene carriers.

  2. Effect of Temperature on the Protonation of the TALSPEAK Ligands: Lactic and Diethylenetrinitropentaacetic Acids

    SciTech Connect

    Tian, Guoxin; Rao, Linfeng

    2009-10-20

    The protonation reactions of two ligands that play important roles in the TALSPEAK process for the separation of trivalent actinides from lanthanides, lactic acid and diethylenetrinitropentaacetic acid (DTPA), have been studied at variable temperatures. The protonation constants at 10-70 C were determined by titration potentiometry and the protonation enthalpies were determined at 25 C by titration microcalorimetry. The protonation constants remain essentially unchanged (25-70 C) within the experimental uncertainties, indicating that the effect of temperature on the protonation of lactate is insignificant. In contrast, the protonation constants of DTPA (log {beta}H's) generally decrease as the temperature is increased. Results from this study indicate that the effect of temperature on the protonation of DTPA could alter the speciation of metal ions (actinides and lanthanides) in the TALSPEAK system, since lower values of log{beta}H at higher temperatures suggest that the hydrogen ions would compete less strongly with the metal ions for the complexation of DTPA at higher temperatures.

  3. Enhancement of radiopharmaceutical excretion by chemical interventions

    SciTech Connect

    Oster, Z.H.; Som, P.; Brill, A.B.; Sacker, D.F.; Atkins, H.L.

    1982-01-01

    The goal was to find methods of decreasing the radiation dose after radionuclide studies, by giving a compound that will increase the rate of excretion of the radionuclide. Sprague - 1 Dawley rats were given Tc-99m pertechnetate, Ga-67 citrate or Tl-201 chloride intravenously followed at intervals of 1 to 24 hours by one of the following compounds: desferroxamine (DFO), 2,3-dimercapto-1-propanol (BAL), triethylene tetraamine hexaacetic acid (TETHA), stannous tartarate, bleomycin (BLEO), 2,3-dimercaptosuccinic acid (DMSA), diethylene-triaminepentaacetic acid (DTPA), DTPA+SnCl.2H/sub 2/O, dihydroxybenzoic acid (DHB), and ferric-cyanoferrate (IT)(Prussian blue, PB). All the agents except PB are chelators. Some of these agents enhance excretion through the urinary tract (DFO), while most are excreted through the bile. PB was shown to increase Cs excrection through the G.I. tract. (ACR)

  4. The correlation between effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with renal scintigraphy 99mTc-DTPA study

    NASA Astrophysics Data System (ADS)

    Ratnasari, D.; Nazir, F.; Toresano, L. O. H. Z.; Pawiro, S. A.; Soejoko, D. S.

    2016-03-01

    The prevalence of chronic renal diseases in Indonesia has an increasing annual trend, because it is frequently unrecognized and often co-exists with other disease. GFR and ERPF are parameters currently utilized to estimate renal function at routine renal scintigraphy 99m-Tc DTPA study. This study used 99m-Tc DTPA to measure GFR and ERPF. The purpose of this study was to find the correlation between ERPF and GFR, for ERPF analysis with Schlegel's method, and GFR analysis with Gate's method, as well as to find correction factor between both variables. Analysis of renal scintigraphy has been performed at Department of Nuclear Medicine Pertamina Center Hospital to thirty patient images acquired from 2014 to 2015 which were analyzed retrospectively data, using gamma camera dual head with counting method from renal scintigraphy 99m-Tc DTPA study. The calculation was executed by means of both display and manual calculation. Pearson's statistical analysis resulted on Positive Correlation for all data, with ERPF and GFR (display) showing Strongly Positive Correlation (r = 0.82; p- value < 0.05). Standard deviation was found to be 27.58 and 107.64 for GFR and ERPF (display), respectively. Our result indicated that the use of 99mTc-DTPA measure ERPF was not recommended.

  5. The Effect of Pressure and Temperature on Separation of Free Gadolinium(III) From Gd-DTPA Complex by Nanofiltration-Complexation Method

    NASA Astrophysics Data System (ADS)

    Rahayu, Iman; Anggraeni, Anni; Ukun, MSS; Bahti, Husein H.

    2017-05-01

    Nowdays, the utilization of rare earth elements has been carried out widely in industry and medicine, one of them is gadolinium in Gd-DTPA complex is used as a contrast agent in a magnetic resonance imaging (MRI) diagnostic to increase the visual contrast between normal tissue and diseased. Although the stability of a given complex may be high enough, the complexation step couldnot have been completed, so there is possible to gadolinium(III) in the complex compound. Therefore, the function of that compounds should be dangerous because of the toxicity of gadolinium(III) in human body. So, it is necessarry to separate free gadolinium(III) from Gd-DTPA complex by nanofiltration-complexation. The method of this study is complexing of Gd2O3 with DTPA ligand by reflux and separation of Gd-DTPA complex from gadolinium(III) with a nanofiltration membrane on the variation of pressures(2, 3, 4, 5, 6 bars) and temperature (25, 30, 35, 40 °C) and determined the flux and rejection. The results of this study are the higher of pressures and temperatures, permeation flux are increasing and ion rejections are decreasing and gave the free gadolinium(III) rejection until 86.26%.

  6. Stabilised 111In-labelled DTPA- and DOTA-conjugated neurotensin analogues for imaging and therapy of exocrine pancreatic cancer.

    PubMed

    de Visser, M; Janssen, P J J M; Srinivasan, A; Reubi, J C; Waser, B; Erion, J L; Schmidt, M A; Krenning, E P; de Jong, M

    2003-08-01

    Neurotensin (NT) receptors are overexpressed in exocrine pancreatic cancer and Ewing's sarcoma. The potential utility of native NT in cancer diagnosis and therapy is, however, limited by its rapid degradation in vivo. Therefore, NT analogues were synthesised with modified lysine and arginine derivatives to enhance stability and coupled either to DTPA, to enable high specific activity labelling with indium-111 for imaging, or to DOTA, to enable high specific activity labelling with beta-emitting radionuclides, such as lutetium-177 and yttrium-90. Based on serum stability (4 h incubation at 37 degrees C in human serum) and receptor binding affinity, the five most promising analogues were selected and further evaluated in in vitro internalisation studies in human colorectal adenocarcinoma HT29 cells, which overexpress NT receptors. All five NT analogues bound with high affinity to NT receptors on human exocrine pancreatic tumour sections. The analogues could be labelled with (111)In to a high specific activity. The (111)In-labelled compounds were found to be very stable in serum. Incubation of HT29 cells with the (111)In-labelled analogues at 37 degrees C showed rapid receptor-mediated uptake and internalisation. The most promising analogue, peptide 2530 [DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH] was further tested in vivo in a biodistribution study using HT29 tumour-bearing nude mice. The results of this study showed low percentages of injected dose per gram tissue of this (111)In-labelled 2530 analogue in receptor-negative organs like blood, spleen, pancreas, liver, muscle and femur. Good uptake was found in the receptor-positive HT29 tumour and high uptake was present in the kidneys. Co-injection of excess unlabelled NT significantly reduced tumour uptake, showing that tumour uptake is a receptor-mediated process. With their enhanced stability, maintained high receptor affinity and rapid receptor-mediated internalisation, the (111)In-labelled DTPA

  7. Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants

    PubMed Central

    Li, Yanping; Li, Rong Cheng; Ye, Qiang; Li, Changgui; Liu, You Ping; Ma, Xiao; Li, Yanan; Zhao, Hong; Chen, Xiaoling; Assudani, Deepak; Karkada, Naveen; Han, Htay Htay; Van Der Meeren, Olivier; Mesaros, Narcisa

    2017-01-01

    ABSTRACT We conducted 3 phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 months of age (Group B). In the Primary study (NCT01086423), 984 healthy infants (randomized 1:1:1) received 3 doses of DTPa-IPV/Hib at 2–3–4 (Group A) or 3–4–5 (Group B) months of age, or concomitant DTPa/Hib and poliomyelitis (IPV) vaccination at 2–3–4 months of age (Control group); 825 infants received a booster dose of DTPa/Hib and IPV at 18–24 months of age (Booster study; NCT01449812). In the Pilot study, unsolicited symptoms were more frequent in Group A (16 versus 1 infant; mostly upper respiratory tract infection and pyrexia); this observation was attributed to an epidemic outbreak of viral infections. Non-inferiority of 3-dose primary vaccination with DTPa-IPV/Hib over separately administered DTPa/Hib and IPV was demonstrated for Group A (primary objective). Similar antibody concentrations were observed in all groups, except for anti-polyribosyl-ribitol phosphate and anti-poliovirus types 1–3 which were higher in DTPa-IPV/Hib recipients. Protective antibody levels against all vaccine antigens remained high until booster vaccination. Three-dose vaccination with DTPa-IPV/Hib had a clinically acceptable safety profile. PMID:27768515

  8. Safety, immunogenicity and persistence of immune response to the combined diphtheria, tetanus, acellular pertussis, poliovirus and Haemophilus influenzae type b conjugate vaccine (DTPa-IPV/Hib) administered in Chinese infants.

    PubMed

    Li, Yanping; Li, Rong Cheng; Ye, Qiang; Li, Changgui; Liu, You Ping; Ma, Xiao; Li, Yanan; Zhao, Hong; Chen, Xiaoling; Assudani, Deepak; Karkada, Naveen; Han, Htay Htay; Van Der Meeren, Olivier; Mesaros, Narcisa

    2017-03-04

    We conducted 3 phase III, randomized, open-label, clinical trials assessing the safety, reactogenicity (all studies), immunogenicity (Primary vaccination study) and persistence of immune responses (Booster study) to the combined diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Chinese infants and toddlers. In the Pilot study (NCT00964028), 50 infants (randomized 1:1) received 3 doses of DTPa-IPV/Hib at 2-3-4 (Group A) or 3-4-5 months of age (Group B). In the Primary study (NCT01086423), 984 healthy infants (randomized 1:1:1) received 3 doses of DTPa-IPV/Hib at 2-3-4 (Group A) or 3-4-5 (Group B) months of age, or concomitant DTPa/Hib and poliomyelitis (IPV) vaccination at 2-3-4 months of age (Control group); 825 infants received a booster dose of DTPa/Hib and IPV at 18-24 months of age (Booster study; NCT01449812). In the Pilot study, unsolicited symptoms were more frequent in Group A (16 versus 1 infant; mostly upper respiratory tract infection and pyrexia); this observation was attributed to an epidemic outbreak of viral infections. Non-inferiority of 3-dose primary vaccination with DTPa-IPV/Hib over separately administered DTPa/Hib and IPV was demonstrated for Group A (primary objective). Similar antibody concentrations were observed in all groups, except for anti-polyribosyl-ribitol phosphate and anti-poliovirus types 1-3 which were higher in DTPa-IPV/Hib recipients. Protective antibody levels against all vaccine antigens remained high until booster vaccination. Three-dose vaccination with DTPa-IPV/Hib had a clinically acceptable safety profile.

  9. Unexpected side products in the conjugation of an amine-derivatized morpholino oligomer with p-isothiocyanate benzyl DTPA and their removal.

    PubMed

    Liu, Guozheng; Dou, Shuping; Liu, Yuxia; Liang, Minmin; Chen, Ling; Cheng, Dengfeng; Greiner, Dale; Rusckowski, Mary; Hnatowich, Donald J

    2011-02-01

    In connection with pretargeting, an amine-derivatized morpholino phosphorodiamidate oligomer (NH(2)-cMORF) was conjugated conventionally with p-isothiocyanate benzyl-DTPA (p-SCN-Bn-DTPA). However, after (111)In radiolabeling, unexpected label instability was observed. To understand this instability, the NH(2)-cMORF and, as control, the native cMORF without the amine were conjugated in the conventional manner. Surprisingly, the (111)In labeling of the native cMORF conjugate was equally effective as that of the NH(2)-cMORF conjugate (>95%) despite the absence of the amine group. Furthermore, heating the radiolabeled NH(2)-cMORF and native cMORF conjugates resulted in a 35% loss and a complete loss of the label, respectively. Since the (111)In labeled DTPA is known to be stable, the instability in both cases must be due to some unstable association of DTPA to the cMORF, presumably unstable association to some endogenous sites in cMORF. Based on this assumption, a postconjugation-prepurification heating step was introduced, and labeling efficiency and stability were again investigated. By introducing the heating step, the side products were dissociated, and after purification and labeling, the NH(2)-cMORF conjugate provided a stable label and high labeling efficiency with no need for postlabeling purification. The biodistribution of this radiolabeled conjugate in normal mice showed significantly lower backgrounds compared with the labeled unstable native cMORF conjugate. In conclusion, the conventional conjugation procedure to attach the p-SCN-Bn-DTPA to NH(2)-cMORF resulted in side product(s) that were responsible for the (111)In label instability. Adding a postconjugation-prepurification heating step dissociated the side products, improved the label stability and lowered tissue backgrounds in mice. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Graphene Oxide and Gadolinium-Chelate Functionalized Poly(lactic acid) Nanocapsules Encapsulating Perfluorooctylbromide for Ultrasound/Magnetic Resonance Bimodal Imaging Guided Photothermal Ablation of Cancer.

    PubMed

    Li, Zhenglin; Ke, Hengte; Wang, Jinrui; Miao, Zhaohua; Yue, Xiuli

    2016-03-01

    This paper successfully fabricated a novel multifunctional theranostic agent (PFOB@PLA/GO/Gd-DTPA NCs) by loading perfluorooctylbromide (PFOB) into poly(lactic acid) (PLA) nanocapsules (NCs) followed by surface functionalization with graphene oxide (GO) and gadolinium-chelate (Gd-DTPA). It was found that the resulting nanoagent could serve as a contrast agent simultaneously to enhance ultrasound (US) and magnetic resonance imaging (MRI). Benefiting from the strong absorption in the near infrared (NIR) region, the nanocapsules could efficiently kill cancer cells under NIR laser irradiation. Thus, such a single theranostic agent with the combination of realtime US imaging and high-resolution MR imaging could achieve great therapeutic effectiveness without systemic damage to the body. In addition, the cytotoxicity assay on HUVEC cells revealed a good biocompatibility of PFOB@PLA/GO/Gd-DTPA NCs, showing that the versatile nanocapsule system may hold great potential as an effective nanoplatform for contrast enhanced imaging guided photothermal therapy.

  11. Gd-Complexes of New Arylpiperazinyl Conjugates of DTPA-Bis(amides): Synthesis, Characterization and Magnetic Relaxation Properties.

    PubMed

    Ba-Salem, Abdullah O; Ullah, Nisar; Shaikh, M Nasiruzzaman; Faiz, Mohamed; Ul-Haq, Zaheer

    2015-04-29

    Two new DTPA-bis(amide) based ligands conjugated with the arylpiperazinyl moiety were synthesized and subsequently transformed into their corresponding Gd(III) complexes 1 and 2 of the type [Gd(L)H2O]·nH2O. The relaxivity (R1) of these complexes was measured, which turned out to be comparable with that of Omniscan®, a commercially available MRI contrast agent. The cytotoxicity studies of these complexes indicated that they are non-toxic, which reveals their potential and physiological suitability as MRI contrast agents. All the synthesized ligands and complexes were characterized with the aid of analytical and spectroscopic methods, including elemental analysis, 1H-NMR, FT-IR, XPS and fast atom bombardment (FAB) mass spectrometry.

  12. Dosimetry of (99m)Tc (DTPA, DMSA and MAG3) used in renal function studies of newborns and children.

    PubMed

    Arteaga, Marcial Vásquez; Caballero, Víctor Murillo; Rengifo, Kelman Marín

    2017-07-28

    The dose to kidneys of newborns and 1-year old children was calculated using the MIRD methodology. In order to perform renal studies radiopharmaceutical like (99m)Tc-DTPA, (99m) Tc-MAG3 and (99m)Tc-DMSA are used. Here, besides the anatomic and structure information of kidneys another data are provided in benefit of patient, however during the radioisotope decay emitted radiations delivers, totally or partially, their energy. Therefore is important to estimate the internal radiation dose of the organs. The largest dose to kidneys comes from the self-dose and it is due to the charged particles emitted during (99m)Tc decay. From the three radiopharmaceutical here used the largest dose to kidneys is due to (99m)Tc-DMSA, and the smaller dose is due to (99m)Tc-MAG3. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Investigation of the usefulness of NTA, EDTA and DTPA in separation of some platinum metals on cellulose exchangers.

    PubMed

    Brajter, K; Słonawska, K

    1980-09-01

    The possibility of using NTA, EDTA and DTPA as complexing agents for separation of some platinum group ions on cellulose ion-exchangers has been investigated. The greatest differences in the affinities of Pd(II) and Pt(IV) toward the cellulose ion-exchangers are obtained in the presence of DPTA, Cellex D (as ion-exchanger) in hydroxide form. The column separation of Pd(II) from Pt(IV), Rh(III) from Pd(II) and of a Rh(III)Pd(II)Pt(IV) mixture can be achieved with DPTA and chloride solutions. The method can be for determination of the components of RhPdPt alloys.

  14. Evaluation of a maleimido derivative of CHX-A” DTPA for site-specific labeling of Affibody molecules

    PubMed Central

    Tolmachev, Vladimir; Xu, Heng; Wållberg, Helena; Ahlgren, Sara; Hjertman, Magnus; Sjöberg, Anna; Sandström, Mattias; Abrahmsén, Lars; Brechbiel, Martin W.; Orlova, Anna

    2008-01-01

    Affibody molecules are a new class of small targeting proteins based on a common threehelix bundle structure. Affibody molecules binding a desired target may be selected using phage-display technology. An Affibody molecule ZHER2:342 binding with subnanomolar affinity to the tumor antigen HER2 has recently been developed for radionuclide imaging in vivo. Introduction of a single cysteine into the cysteine-free Affibody scaffold provides a unique thiol group for site-specific labeling of recombinant Affibody molecules. The recently developed maleimido-CHX-A” DTPA was site-specifically conjugated at the C-terminal cysteine of ZHER2:2395-C, a variant of ZHER2:342, providing a homogenous conjugate with a dissociation constant of 56 pM. The yield of labeling with 111In was > 99% after 10 min at room temperature. In vitro cell tests demonstrated specific binding of 111In-CHX-A” DTPAZ2395-C to HER2-expressing cell-line SKOV-3 and good cellular retention of radioactivity. In normal mice, the conjugate demonstrated rapid clearance from all non-specific organs except kidney. In mice bearing SKOV-3 xenografts, the tumor uptake of 111In-CHX-A” DTPAZ2395-C was 17.3 ± 4.8 % IA/g and the tumor-to-blood ratio 86 ± 46 (4 h post-injection). HER2-exprssing xenografts were clearly visualized 1 h post-injection. In conclusion, coupling of maleimido-CHX-A” DTPA to cysteine-containing Affibody molecules provides welldefined uniform conjugate, which can be rapidly labeled at room temperature and provides high-contrast imaging of molecular targets in vivo. PMID:18620447

  15. Alteration of tissue disposition of cadmium by chelating agents. [Mice; rats

    SciTech Connect

    Klaassen, C.D.; Waalkes, M.P.; Cantilena, L.R. Jr.

    1984-03-01

    The effect of several chelating agents (diethyldithiocarbamic acid, DDC; nitrilotriacetic acid, NTA; 2,3-dimercaptopropanol, BAL; d,l-penicillamine, PEN; 2,3-dimercaptosuccinic acid, DMSA; ethylenediaminetetraacetic acid, EDTA; and diethylenetriaminepentaacetic acid, DTPA) on the toxicity, distribution and excretion of cadmium (Cd) was determined in mice. When chelators were administered immediately after Cd, significant increases in survival were noted after treatment with DMSA, EDTA, and DTPA. DTPA, followed by EDTA and then DMSA, were consistently the most effective in decreasing the tissue concentrations of Cd and increasing the excretion of Cd. NTA, BAL, DDC and PEN had no beneficial effects. To determine the role of MT in the acute decrease in chelator efficacy following Cd poisoning, rats were injected IV with Cd followed by DTPA at various times after Cd. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal metallothionein (MT) did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D failed to eliminate this decreased DTPA effectiveness. Therefore, it appears that MT does not play an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The effect of repeated daily administration of chelators on the distribution and excretion of Cd was studied by administering chelators daily for 5 days starting 48 hr after Cd. DTPA, EDTA, DMSA and BAL significantly increased the urinary elimination of Cd. Thus, mobilization of Cd into urine occurs with repeated chelation therapy, which may decrease tissue concentrations of Cd and reduce the toxicity of the metal. 4 references, 15 figures, 2 tables.

  16. Technetium-99m-L,L-ethylenedicysteine is more effective than technetium-99m diethylenetriamine penta-acetic acid for excluding obstruction in patients with pyelocalicinal dilation.

    PubMed

    Lima, Mariana C L; de Lima, Marcelo Lopes; Pepe, Carlos F V; Etchebehere, Elba C S C; Santos, Allan O; Amorim, Bárbara J; Camargo, Edwaldo E; Ferreira, Ubirajara; Palma, Paulo C R; Ramos, Celso D

    2010-08-01

    To evaluate the utility of diuretic dynamic renal scintigraphy (DDRS) with technetium-99m-L,L-ethylenedicysteine ((99m)Tc-EC) in patients with indeterminate or possible false-positive results for urinary obstruction by technetium-99m diethylenetriamine penta-acetic acid ((99m)Tc-DTPA) DDRS. A total of 92 patients (63 male; mean age, 16.6 +/- 21.25 years) were studied, with a total of 103 kidneys presenting indeterminate (20/103) or possible false-positive results for obstruction attributable to reduced renal function or severe kidney dilation (83/103) by (99m)Tc-DTPA DDRS (<60% of radiopharmaceutical excreted in 20 minutes-half-time clearance [T(1/2)] >15 minutes). Patients were reimaged after intravenous injection of (99m)Tc-EC, with dynamic images before and after furosemide administration using the same acquisition parameters applied in the previous (99m)Tc-DTPA study. Time interval between (99m)Tc-DTPA and (99m)Tc-EC renograms was 2-64 days. The percentage of excreted material 20 minutes after furosemide was calculated using both radiopharmaceuticals, and were statistically compared using the paired samples t test. The excretion after furosemide injection was 25.3% +/- 18.2% for (99m)Tc-DTPA and 41.2% +/- 26.1% for (99m)Tc-EC, with a statistically significant difference between both radiopharmaceuticals (P <.0001). Using (99m)Tc-EC obstruction was excluded in 36 of 103 kidneys, which excreted >60%. A total of 10 of 83 kidneys (12.0%) with an obstructive pattern by (99m)Tc-DTPA study turned out to be indeterminate by (99m)Tc-EC DDRS. There was an agreement between (99m)Tc-EC and (99m)Tc-DTPA studies in 54 of 83 kidneys with obstructive (65.1%) and in 3 of 20 (15.0%) with indeterminate patterns. (99m)Tc-EC was more effective than (99m)Tc-DTPA for excluding obstruction, presenting less false-positive and indeterminate results. (99m)Tc-EC can substitute (99m)Tc-DTPA to evaluate patients with urinary tract dilation. Copyright (c) 2010 Elsevier Inc. All rights

  17. Comparison of Performance of Improved Serum Estimators of Glomerular Filtration Rate (GFR) to (99m)Tc-DTPA GFR Methods in Patients with Hepatic Cirrhosis.

    PubMed

    Haddadin, Zaid; Lee, Vivian; Conlin, Christopher; Zhang, Lei; Carlston, Kristi; Morrell, Glen; Kim, Daniel; Hoffman, John M; Morton, Kathryn

    2017-03-01

    Glomerular filtration rate (GFR) measurements are critical in patients with hepatic cirrhosis but potentially erroneous when based on serum creatinine. New equations for estimated GFR (eGFR) have shown variable performance in cirrhotics, possibly because of inaccuracies in reference methods for measured GFR (mGFR). The primary objective was to compare the performance of 4 improved eGFR equations with a 1-compartment, 2-sample plasma slope intercept (99m)Tc-DTPA mGFR method to determine whether any of the eGFR calculations could replace plasma (99m)Tc-DTPA mGFR in patients with cirrhosis. The secondary objective was to test the hypothesis that mGFR using voluntary voided urine collections introduces error compared with plasma-only methods. Methods: Fifty-four patients with hepatic cirrhosis underwent mGFR determinations from 2 plasma samples at 1 and 3 h after intravenous administration of 185 MBq of (99m)Tc-DTPA. GFR was also generated by a UV/P calculation derived from blood and urine samples. These mGFRs were compared with the eGFRs generated by 4 estimating equations: MDRD (Modified Diet in Renal Disease), CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) (serum creatinine [SCr]), CKD-EPI (cystatin [CysC]), and CKD-EPI (CysC+SCr). eGFRs were compared with mGFRs by Pearson correlation, precision, bias, percentage bias, and accuracy (eGFRs varying by <10% [p10], <20% [p20] or <30% [p30] from the corresponding mGFR). Results: All eGFRs showed poorer performance when the UV/P (99m)Tc-DTPA mGFR was used as the reference than when the plasma (99m)Tc-DTPA mGFR was used. When compared with the plasma (99m)Tc-DTPA mGFR method, the performance of all eGFR equations was superior to most published reports. There was a moderately good positive correlation between eGFRs and mGFRs. When compared with plasma (99m)Tc-DTPA mGFR, precision of eGFRs was in the range of 14-20 mL/min and showed a negligible bias. Compared with the plasma (99m)Tc-DTPA mGFR, CKD-EPI (Cys

  18. Distribution of pancreatic B cell imaging agent 99mTc-DTPA-NGN2 in the body and animal experimental research on pancreatic B cell functional imaging

    PubMed Central

    Liu, Zhi-Hua; Xie, Ying; Tang, Jun; Liu, Chun-Feng

    2016-01-01

    Purpose: To explore the feasibility of the application of 99mTc-DTPA-Nateglinide as a nuclear medicine imaging agent for evaluating pancreatic B cell function. Methods: (1) Distribution of the experiment: Forty-two mice were selected and divided into seven groups. Each mice was injected with 3.7 MBq (100 μCi) of 99mTc-DTPA-NGN2 from the vena caudalis and was sacrificed by bloodletting at five minutes, 15 minutes, 30 minutes, one hour, two hours, four hours and six hours, respectively. Then, their tissues and organs such as the heart, liver, spleen, brain, kidneys, bones, small bowels, stomach and pancreas,and blood were collected, weighted, and their radioactivity was tested. Subsequently, the percentage injection dose rate (%ID/g) per gram of tissue was calculated. (2) Imaging experiment: Thirty-five mice were selected and divided into seven groups. Each was injected with 18.5 MBq (100 μCi) of 99mTc-DTPA-NGN2 from the vena caudalis and imaging were conducted at the same time as above. (3) Forty-eight Wistar rats were attained and randomly divided into four groups. The first group served as the healthy control group, while the second, third and fourth groups were diabetic model groups induced by intraperitoneally injecting STZ at different doses. Each group was injected with 99mTc-DTPA-Nateglinide from the vena caudalis, and radiological evaluations were conducted at 30 minutes, one hour, 1.5 hours and two hours, respectively. The data obtained were estimated using a correlation comparison with the levels of insulin and immunohistochemical count of beta cells. Results: The 99mTc-DTPA-Nateglinide demonstrated good imaging in the pancreases of mice and rats, and was positively correlated to the level of insulin and the number of pancreatic beta cells. Conclusion: Pancreatic beta cell imaging using 99mTc-DTPA-Nateglinide may be a method to evaluate pancreatic beta cell function. PMID:27186309

  19. Metabolomic Analysis of N-acetylcysteine Protection of Injury from Gadolinium-DTPA Contrast Agent in Rats with Chronic Renal Failure.

    PubMed

    Wan, Chuanling; Xue, Rong; Zhan, Youyang; Wu, Yijie; Li, Xiaojing; Pei, Fengkui

    2017-09-01

    Gadolinium-based contrast agents (GBCAs) are frequently used to enhance the diagnostic efficacy of magnetic resonance imaging. On the other hand, the association between GBCA administration in patients with advanced renal disease and nephrogenic systemic fibrosis (NSF) was also noted. NSF is a systemic disorder characterized by widespread tissue fibrosis that may lead to death. N-acetylcysteine (NAC) protects rats from injury induced by gadolinium-based contrast agents, but the underlying mechanisms remain unclear. In this study, a nuclear magnetic resonance-based metabolomic approach was used to systematically investigate the protective effects of NAC on Gd-DTPA-induced injury. Thirty-two male Sprague-Dawley rats were given adenine (200 mg·kg(-1) body weight) by oral gavage once a day for 3 weeks to induce chronic renal failure (CRF). NAC (600 mg/L in drinking water for 9 days) pretreatment was initiated 2 days before Gd-DTPA injection (a single tail vein injection, 2 mmol/kg body weight). Serum and liver samples were collected on day 7 after Gd-DTPA injection. By study design, the serum and hepatic metabolic changes of rats were measured in four groups of eight each: CRF, CRF-Gd, CRF-Gd-NAC, and CRF-NAC. Gd-DTPA administration to rats with CRF resulted in disturbances of several metabolic pathways, including glucose, lipid, glutamate, choline, gut microbiota, one-carbon, and purine metabolism. NAC pretreatment reversed the abundance changes of high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, glutamate, glutamine, oxidized glutathione, choline, phosphocholine, glycerophosphocholine, trimethylamine, and trimethylamine-N-oxide induced by Gd-DTPA. It is noteworthy, however, that the ameliorating effects of NAC on the disturbance of glutamate, choline, and gut microbiota metabolism may be specific to Gd-DTPA. In all, these findings could be potentially useful to decipher the underlying mechanisms of NAC protective effects from

  20. Evaluation of [(111/114m)In]CHX-A''-DTPA-ZHER2:342, an affibody ligand coniugate for targeting of HER2-expressing malignant tumors.

    PubMed

    Orlova, A; Rosik, D; Sandström, M; Lundqvist, H; Einarsson, L; Tolmachev, V

    2007-12-01

    Radionuclide imaging of the HER2 receptor, which is a target for trastuzumab therapy, can provide important diagnostic information. Further, targeting radionuclide therapy might be an option for treatment of HER2 expressing tumors. The phage-display selected Affibody ligand Z(HER2:342), which binds to HER2 with an affinity of 22 pM, may here play an important role. The small size of the Z(HER2:342), 7.5 kDa, enables quick tumor localization and fast blood clearance. Earlier, successful targeting of HER2-expressing xenografts using Z(HER2:342) labeled using [(111)In]benzyl-DTPA was reported. By changing to the CHX-A''-DTPA chelator, the stability and labeling kinetics of the radiometal-Z(HER2:342) conjugate can be improved. The aim of this study was to evaluate the labeling of the CHX-A''-DTPA-Z(HER2:342) conjugate with (111)In for diagnostic imaging and with (114m)In for locoregional radionuclide therapy. The isothiocyanate derivative of CHX-A''-DTPA was coupled to Z(HER2:342) in alkaline conditions at 37 degrees C. The conjugate was labeled with both (111)In and (114m)In and evaluated in vitro and in vivo. Labeling with (111)In and (114m)In provided >95% yield after 30 min at RT. Specific radioactivity was 0.5 and 12 MBq/nmol, for (114m)In and (111)In, respectively. The radiolabeled conjugates demonstrated specific binding to HER2 expressing SKOV-3 cells. In mice bearing SKOV-3 xenografts, the tumor uptake of [(111)In]CHX-A''-DTPA-Z(HER2:342) 4 h postinjection was 10.3+/-3.6% IA/g and tumor-to-blood ratio about 190. [(111)In]CHX-A''-DTPA-Z(HER2:342) is a promising candidate for the visualization of HER2 expression in malignant tumors. Labeled with (114m)In it could also be used for locoregional treatment of HER2 expressing tumors.

  1. Radionuclide evaluation of renal transplants

    SciTech Connect

    Dubovsky, E.V.; Russell, C.D.

    1988-07-01

    In this review article, the following topics are treated: the radiopharmaceuticals /sup 99m/Tc-diethylenetriaminepentaacetic acid (DTPA), /sup 131/I-orthoiodohippurate (OIH), /sup 99m/Tc-mercaptoacetyltriglycine (MAG3), /sup 67/Ga-citrate, radioiodinated fibrinogen, /sup 99m/Tc-sulfur colloid, 111In-labelled white cells and platelets; gamma camera methods based on images, on first pass and on tubular transit; blood clearance methods; and the diagnosis of surgical complications, acute rejection (AR), acute tubular necrosis (ATN), chronic rejection (CR), and cyclosporine-A (CYA) toxicity. 94 references.

  2. Micelles Based on Biodegradable Poly(L-glutamic acid)-b-Polylactide with Paramagnetic Gd Ions Chelated to the Shell Layer as a Potential Nanoscale MRI-Visible Delivery System

    PubMed Central

    Zhang, Guodong; Zhang, Rui; Wen, Xiaoxia; Li, Li; Li, Chun

    2008-01-01

    There is much interest in the development of nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly(L-glutamic acid)-b-polylactide (PG-b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. (PG-b-PLA) was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed by ring opening polymerization of benzyl glutamate N-carboxylic anhydride. The metal chelator p-aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to the side chain carboxylic acids of poly(L-glutamic acid). The resulting copolymer formed spherical micelles in aqueous solution with an average diameter of 230 nm at pH 7.4. The size of PG(DTPA)-b-PLA micelles decreased with increasing pH value. DTPA-Gd chelated to the shell layer of the micelles exhibited significantly higher spin-lattice relaxivity (r1) than a small-molecular-weight MRI contrast agent, indicating that water molecules could readily access the Gd ions in the micelles. Because of the presence of multiple carboxylic acid functional groups in the shell layer, polymeric micelles based on biodegradable PG(DTPA-Gd)-b-PLA may be a suitable platform for the development of MRI-visible, targeted nanoscale drug delivery systems. PMID:18047289

  3. New Developments in the Pathogenesis of Smoke Inhalation-Induced Pulmonary Edema

    PubMed Central

    Witten, Mark L.; Quan, Stuart F.; Sobonya, Richard E.; Lemen, Richard J.

    1988-01-01

    Smoke inhalation causes most of the deaths in fire-related injuries, with pulmonary edema as a major determinant in the outcome of smoke-inhalation injury. The pathophysiology of pulmonary edema is thought to be related to the products of incomplete combustion. Damage to the integrity of the alveolar epithelium is one of the determinants of the development of smoke-induced pulmonary edema. In recent studies using lung clearance of aerosolized pentetic acid (DTPA [diethylenetriaminepentaacetic acid]) labeled with technetium Tc 99m to assess the permeability of the alveolar epithelium, several factors were identified that may increase a person's susceptibility to smoke-induced acute lung injury. These are increased initial alveolar permeability and alterations in the number and activity of alveolar macrophages. Clinical measurement of 99mTcDTPA clearance may provide a sensitive and convenient method for the early detection and serial assessment of smoke-induced alveolar epithelial permeability changes. Images PMID:3277334

  4. Auger electron-emitting (111)In-DTPA-NLS-CSL360 radioimmunoconjugates are cytotoxic to human acute myeloid leukemia (AML) cells displaying the CD123(+)/CD131(-) phenotype of leukemia stem cells.

    PubMed

    Gao, Catherine; Leyton, Jeffrey V; Schimmer, Aaron D; Minden, Mark; Reilly, Raymond M

    2016-04-01

    Chimeric IgG1 monoclonal antibody CSL360 recognizes the CD123(+)/CD131(-) phenotype expressed by leukemic stem cells (LSC). Auger electron-emitting (111)In-DTPA-NLS-CSL360 radioimmunoconjugates incorporating nuclear translocation sequence (NLS) peptides bound specifically to Raji cells transfected with CD123 and exhibited a KD of 11nmols/L in a competition receptor-binding assay using CD123-transfected CHO cells. (111)In-DTPA-NLS-CSL360 was bound, internalized and transported to the nucleus of human AML-5 myeloid leukemia cells. The clonogenic survival of AML-5 cells was reduced by (111)In-DTPA-NLS-CSL360 up to 3.7-fold. Isotype control (111)In-DTPA-chIgG1 was 2-fold less cytotoxic, and unlabeled CSL360, DTPA-NLS-CSL360 or free (111)In acetate did not decrease cell survival. These results are promising for further evaluation of (111)In-DTPA-NLS-CSL360 for Auger electron radioimmunotherapy of AML targeting the critical LSC subpopulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Solvent extraction separation of trivalent lanthanide and actinide ions using an aqueous aminomethanediphosphonic acid.

    SciTech Connect

    Jensen, M. P.

    1998-10-14

    The possibility of separating the trivalent lanthanides, represented by EU{sup 3+}, and actinides, represented by Cf{sup 3+}, using HDEHP in toluene and an aqueous phase containing N-piperidinomethane-1,1-diphosphotic acid, PMDPA, has been investigated. This modified aqueous phase offers potential advantages over the diethylenetriaminepentaacetic acid based TALSPEAK process because of the improved complexation properties of PMDPA in acidic solutions, and the ability to decompose PMDPA before disposal. Extraction experiments were conducted at 25 C in 2 M NaClO{sub 4} between -log [H{sup +}] 1 and 2. The studies enabled us to derive the aqueous phase speciation, the stability constants of the aqueous complexes, and the Cf/Eu separation factors. Despite the presence of an amino group in PMDPA that should favor the retention of the actinides in the aqueous phase, the Cf/Eu separation factors are near unity under the conditions studied.

  6. Threshold Doses for Focal Liver Reaction After Stereotactic Ablative Body Radiation Therapy for Small Hepatocellular Carcinoma Depend on Liver Function: Evaluation on Magnetic Resonance Imaging With Gd-EOB-DTPA

    SciTech Connect

    Sanuki, Naoko; Takeda, Atsuya; Oku, Yohei; Eriguchi, Takahisa; Nishimura, Shuichi; Aoki, Yosuke; Mizuno, Tomikazu; Iwabuchi, Shogo; Kunieda, Etsuo

    2014-02-01

    Purpose: Focal liver reaction (FLR) appears on radiographic images after stereotactic ablative body radiation therapy (SABR) in patients with hepatocellular carcinoma (HCC) and chronic liver disease. We investigated the threshold dose (TD) of FLR and possible factors affecting the TD on gadoxetate acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). Methods and Materials: In 50 patients who were treated with SABR for small HCC and followed up by MRI for >6 months, FLR, seen as a hypointense area, was evaluated on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. The follow-up MRI with the largest extent of FLR was fused to the planning computed tomography (CT) image, and patients with good image fusion concordance were eligible. After delineating the border of the FLR manually, a dose–volume histogram was used to identify the TD for the FLR. Clinical and volumetric factors were analyzed for correlation with the TD. Results: A total of 45 patients were eligible for analysis with a median image fusion concordance of 84.9% (range, 71.6-95.4%). The median duration between SABR and subsequent hepatobiliary phase MRI with the largest extent of FLR was 3 months (range, 1-6 months). The median TD for FLR was 28.0 Gy (range, 22.3-36.4 Gy). On univariate analysis, pre-treatment Child-Pugh (CP) score and platelet count were significantly correlated with the TD. On multiple linear regression analysis, CP score was the only parameter that predicted TD. Median TDs were 30.5 Gy (range, 26.2.3-36.4 Gy) and 25.2 Gy (range, 22.3-27.5 Gy) for patients with CP-A and CP-B disease, respectively. Conclusion: The TD was significantly correlated with baseline liver function. We propose 30 Gy for CP-A disease and 25 Gy for CP-B disease in 5 fractions as TDs for FLR after SABR for patients with HCC and chronic liver disease. Use of these TDs will help to predict potential loss of liver tissue after SABR.

  7. Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein

    SciTech Connect

    Moerlein, S.M.; Daugherty, A.; Sobel, B.E.; Welch, M.J. )

    1991-02-01

    Low-density lipoprotein (LDL) labeled with either gallium-68 ({sup 68}Ga) or indium-111 ({sup 111}In) was evaluated as a potential PET or SPECT radiopharmaceutical for determination of hepatic lipoprotein metabolism in rabbits. Gallium-68 or {sup 111}In was linked to LDL via diethylenetriaminepentaacetic acid (DTPA) with a 25-70% radiochemical yield. Studies in vivo that compared {sup 68}Ga- or {sup 111}In-DTPA-LDL with dilactitol-({sup 125}I)-tyramine LDL and 131I-LDL showed that both {sup 68}Ga- and {sup 111}In-labeled LDL behaved as residualizing radiotracers. Localization of radioactivity within the liver of normal rabbits was visualized clearly with ({sup 68}Ga)DTPA-LDL by PET and with ({sup 111}In)DTPA-LDL by gamma scintigraphy. Significant differences were observed in hepatic uptake of normal compared with hypercholesterolemic rabbits in which low-capacity LDL receptor-mediated catabolism was saturated. Gallium-68 and {sup 111}In-DTPA-LDL are attractive radiopharmaceuticals for noninvasive delineation of tissue LDL metabolism under normal and pathophysiologic conditions.

  8. Evaluation of residual functional lung volume on Tc-99m DTPA aerosol ventilation and Tc-99m MAA perfusion scintigraphy in primary ciliary dyskinesia (Kartagener syndrome).

    PubMed

    Chen, Yu-Wen; Chang, Chin-Chuan; Lai, Yung-Chuang; Lu, Chia-Ying; Dai, Zen-Kong

    2008-12-01

    Kartagener syndrome is diagnosed as sinusitis, bronchitis (bronchiectasis), and situs inversus by the clinical features. It is a subclass of primary ciliary dyskinesia (PCD) disease. A 12-year-old girl who had frequent upper and lower airway infections since birth, which was confirmed as Kartagener syndrome by HRCT imaging. We present the residual functional lung volume and mucociliary clearance findings seen on Tc-99m DTPA aerosol ventilation and Tc-99m MAA perfusion scintigraphy.

  9. Evaluation of the effects of toluene inhalation on alveolar epithelial permeability by 99mTc-DTPA inhalation scintigraphy in automobile painters.

    PubMed

    Cerci, Sevim Sureyya; Ozturk, Onder; Sutcu, Recep; Ozbek, Feride Meltem; Baydar, Cetin Lutfi; Yildiz, Mustafa; Akkaya, Ahmet; Delibas, Namk

    2008-01-01

    The main component of paint thinner used in industry is toluene diisocyanate (TDI) which can cause occupational asthma in 5-10% of exposed workers. To investigate the effect of TDI on 99mTc clearance rate of alveolar epithelium and on pulmonary function tests (PFT) in automobile painters, and to determine the relationship between 99mTc-DTPA radioaerosol lung scintigraphy and serum levels of antioxidant enzymes and metalloproteinases (MMPs) of automobile painters. Twenty-eight automobile painters and 13 control subjects were included in the study. 99mTc-DTPA aerosol inhalation scintigraphy and PFT were administered to all subjects. Clearance half-time (T1/2) and penetration index (PI) on the first-minute image after 99mTc-DTPA scintigraphy were calculated. Blood levels of MDA, antioxidant enzymes and metalloproteinases were measured. The mean T1/2 values of automobile painters were longer in both smoker and non-smoker subjects, but the difference was not significant (P>0.05). Although the PFT values decreased in automobile painters, there was no significant difference between each group. Any correlation between spirometric measurements and T1/2 or PI values in non-smoking automobile painters was not detected. Negative correlation among mean T1/2 value and FVC% and FEV1% in smoking automobile painters, and positive correlation between mean T1/2 value and MMP-9, GSH-Px levels in non-smoking automobile painters were detected. Our results suggested that the clearance of 99mTc-DTPA from the lungs of automobile painters was slower than in the control group, but the difference is not statistically significant. This data also supports the observation that TDI occasionally stimulates bronchial changes rather than alveolar changes in automobile painters.

  10. Using the integral spleen method of radiorenogram analysis and a baboon model to compare the diagnostic usefulness of technetium-99m-diethylenetriamine pentaacetic acid to that of various technetium-99m-mercaptoacetyltriglycene formulations and iodine-123-hippuran

    SciTech Connect

    Dormehl, I.C.; Van Wyk, A.; Pilloy, W.; Maree, M.; Knoesen, O.; De Winter, R.; Jacobs, L.; Hoppe, H.C.

    1989-01-01

    In light of the high price of commercially available mercaptoacetyltriglycene (MAG3) it was decided to attempt a local MAG3-formation and to test this against diethylenetriamine pentaacetic acid (DTPA), /sup 123/I-Hippuran, and commercial MAG3 for diagnostic radiorenographic capabilities also in conjunction with furosemide and captopril. A baboon model (n = 6) was used, and the parameters evaluated were obtained by the integral spleen method of radiorenogram analysis. Although the images and parameters pointed to /sup 123/I-Hippuran and commercial MAG3 as the ideal renal scanning agents and to DTPA as the least so, with the local product an acceptable alternative, the differences were not significant enough to warrant either the purchase of the commercial product or the extensive development of the local product. Inexpensive /sup 99m/Tc-DTPA in conjunction with modern computer techniques will probably supply most of the answers.

  11. Effects of lowering the aluminium content of a dTpa vaccine on its immunogenicity and reactogenicity when given as a booster to adolescents.

    PubMed

    Theeten, H; Van Damme, P; Hoppenbrouwers, K; Vandermeulen, C; Leback, E; Sokal, E M; Wolter, J; Schuerman, L

    2005-02-10

    As aluminium in vaccines has been associated with the incidence of local side effects occurring after vaccination, this observer-blind randomised clinical trial was designed to evaluate the effect of lowering the aluminium content of a combined reduced-antigen-content dTpa vaccine on immunogenicity and safety when administered to healthy adolescents aged 10-18 years. A total of 647 subjects were enrolled, 224 (35%) received a dTpa formulation with 0.5 mg aluminium, 209 (32%) a formulation with 0.3 mg aluminium and 214 (33%) a formulation with 0.133 mg aluminium. One month after boostering, all subjects were seroprotected against diphtheria and tetanus toxoids. All subjects were seropositive for anti-FHA and anti-PRN but 4% of the initially seronegatives in both reduced aluminium groups did not seroconvert for anti-PT. Booster responses did not differ significantly between groups for any antibody, but post booster vaccination anti-PT GMC's differed significantly between groups and decreased when vaccine aluminium content decreased. No clear difference between study groups in local or general side effects was demonstrated. The most frequently reported symptoms after vaccination were injection site pain (89.5-90.7%), fatigue (42.1-47.4%) and headache (41.1-45.1%). This study showed that the aluminium content has a specific influence on the immunogenicity of this dTpa vaccine.

  12. Cholangiocarcinoma: spectrum of appearances on Gd-EOB-DTPA-enhanced MR imaging and the effect of biliary function on signal intensity.

    PubMed

    Feng, Shi-Ting; Wu, Ling; Cai, Huasong; Chan, Tao; Luo, Yanji; Dong, Zhi; Zheng, Keguo; Li, Zi-Ping

    2015-02-06

    To describe the Gd-EOB-DTPA-enhanced MRI appearances of cholangiocarcinoma, and evaluate the relative signal intensities (RSIs) changes of major abdominal organs, and investigate the effect of total bilirubin (TB) levels on the RSI. 25 patients with pathologically-proven cholangiocarcinoma underwent Gd-EOB-DTPA-enhanced MRI. The visualization of the biliary system during biliary phase (BP) was observed. RSIs of the abdominal aorta (A), portal vein (V), liver (L), and spleen (S) were measured. On hepatocellular phase (HP), exophytic tumors (n =10) and infiltrative tumors (n =10) were hypointense, polypoid tumors (n = 2) were hypointense, and combined type tumors (n = 3) had mixed appearances. While patients with normal TB levels (≤22 μmol/L, n = 12) had clear visualization of the biliary tree during BP, those with elevated TB levels (>22 μmol/L, n = 13) had obscured or no visualization. In addition, patients with normal TB levels had higher RSIA, RSIV and RSIS than those with elevated TB levels on all dynamic phases (P <0.001), and lower RSIA, RSIV and RSIS on HP and BP (P <0.001). Patients with normal TB levels had higher RSIL than those with elevated TB levels on all phases (P <0.001). RSIs of major abdominal organs reflected underlying biliary function. Cholangiocarcinoma patients with elevated TB levels had delayed excretion of Gd-EOB-DTPA compared with patients with normal TB levels.

  13. Early diagnosis and regional evaluation of radiation mucositis by newly developed TC-99M DTPA labelled agent

    SciTech Connect

    Tamamura, H.; Ohguchi, M.; Higashi, K.

    1994-05-01

    We have developed a new drug for treating acute radiation mucositis which consists of a steroid with potent localized anti-inflammatory effect, and sodium alginate with strong adherence to mucosal surface, and since then we have treated many patients with success. In the present study, we labelled this agent with Tc-99m DTPA, and administered to 10 healthy volunteers and 35 patients with acute radiation mucositis, and determined the values of mean transit time (MTT) and T1/2 from the dynamic phase and the time taken for the mixture to reach to cardia according to Talliefer`s method. Abnormal radionuclide (RN) accumulation in the esophagus was evaluated at 10 minutes after the administration and, the ratio of abnormal RN accumulation count were calculated. In the healthy volunteers, the MTT was 2.67 seconds, T1/2 14.0 seconds, and the time for the drug to reach the stomach 5.25 seconds. Even in the patients with acute radiation mucositis, these values were not significantly different from the healthy controls. However, the images taken at 10 minutes after the administration revealed abnormal RN accumulation corresponding to the irradiated region in all patients. The ratio of this abnormal RN accumulation to the total RN count in the esophagus was 52.48%, the pre-administration RN ratio was 6.45%. None of the healthy volunteers produced abnormal RN accumulation. The ratio of total RN count in the esophagus to pre-administration RN count was only 1.87% in the healthy volunteers, whereas 11.39% in the radiation mucositis group. When Tc-99m DTPA-labelled water was used similarly, the region of radiation esophagitis was not identified on scintigraphy. It was thus suggested that diagnosis of radiation mucositis could be made only with this new agent of high viscosity and very strong mucous adhesive property. Owing to its repeatability and simplicity, this new agent seemed to be useful to make the early diagnosis and regional evaluation of radiation mucositis possible.

  14. Proteinuria, 99mTc-DTPA Scintigraphy, Creatinine-, Cystatin- and Combined-Based Equations in the Assessment of Chronic Kidney Disease

    PubMed Central

    Trimarchi, Hernán; Muryan, Alexis; Toscano, Agostina; Martino, Diana; Forrester, Mariano; Pomeranz, Vanesa; Lombi, Fernando; Young, Pablo; Raña, María Soledad; Karl, Alejandra; Alonso, M.; Dicugno, Mariana; Fitzsimons, Clara

    2014-01-01

    Background. Precise estimation of the glomerular filtration rate (GFR) and the identification of markers of progression are important. We compared creatinine, cystatin, and combined CKD-EPI equations with 99mTc-DTPA scintigraphy to measure GFR and proteinuria as markers of progression. Methods. Cross-sectional, observational study including 300 subjects. CKD was classified by 99mTc-DTPA scintigraphy. Determinations. Creatinine, 24-hour creatinine clearance, cystatin, Hoek formula, and creatinine, cystatin, and combined CKD-EPI equations. Results. In the global assessment, creatinine CKD-EPI and combined CKD-EPI equations yielded the highest correlations with 99mTc-DTPA: ρ = 0.839, P < 0.0001 and ρ = 0.831, P < 0.0001. Intergroup analysis versus 99mTc-DTPA: control G, creatinine clearance ρ = 0.414, P = 0.013; G3, combined CKD-EPI ρ = 0.5317, P < 0.0001; G4, Hoek ρ = 0.618, P < 0.0001, combined CKD-EPI ρ = 0.4638, P < 0.0001; and G5, creatinine clearance ρ = 0.5414, P < 0.0001, combined CKD-EPI ρ = 0.5288, P < 0.0001. In the global assessment, proteinuria displayed the highest significant correlations with cystatin (ρ = 0.5433, P < 0.0001) and cystatin-based equations (Hoek: ρ = −0.5309, P < 0.0001). When GFR < 60 mL/min: in stage 3, proteinuria-cystatin (ρ = 0.4341, P < 0.0001); proteinuria-Hoek (ρ = −0.4105, P < 0.0001); in stage 4, proteinuria-cystatin (ρ = 0.4877, P < 0.0001); proteinuria-Hoek (ρ = −0.4877, P = 0.0026). Conclusions. At every stage of GFR < 60 mL/min, cystatin-based equations displayed better correlations with 99mTc-DTPA. Proteinuria and cystatin-based equations showed strong associations and high degrees of correlation. PMID:24977136

  15. In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent.

    PubMed

    Dewi, Novriana; Mi, Peng; Yanagie, Hironobu; Sakurai, Yuriko; Morishita, Yasuyuki; Yanagawa, Masashi; Nakagawa, Takayuki; Shinohara, Atsuko; Matsukawa, Takehisa; Yokoyama, Kazuhito; Cabral, Horacio; Suzuki, Minoru; Sakurai, Yoshinori; Tanaka, Hiroki; Ono, Koji; Nishiyama, Nobuhiro; Kataoka, Kazunori; Takahashi, Hiroyuki

    2016-04-01

    A more immediate impact for therapeutic approaches of current clinical research efforts is of major interest, which might be obtained by developing a noninvasive radiation dose-escalation strategy, and neutron capture therapy represents one such novel approach. Furthermore, some recent researches on neutron capture therapy have focused on using gadolinium as an alternative or complementary for currently used boron, taking into account several advantages that gadolinium offers. Therefore, in this study, we carried out feasibility evaluation for both single and multiple injections of gadolinium-based MRI contrast agent incorporated in calcium phosphate nanoparticles as neutron capture therapy agent. In vivo evaluation was performed on colon carcinoma Col-26 tumor-bearing mice irradiated at nuclear reactor facility of Kyoto University Research Reactor Institute with average neutron fluence of 1.8 × 10(12) n/cm(2). Antitumor effectivity was evaluated based on tumor growth suppression assessed until 27 days after neutron irradiation, followed by histopathological analysis on tumor slice. The experimental results showed that the tumor growth of irradiated mice injected beforehand with Gd-DTPA-incorporating calcium phosphate-based nanoparticles was suppressed up to four times higher compared to the non-treated group, supported by the results of histopathological analysis. The results of antitumor effectivity observed on tumor-bearing mice after neutron irradiation indicated possible effectivity of gadolinium-based neutron capture therapy treatment.

  16. Reliability of single kidney glomerular filtration rate measured by a 99mTc-DTPA gamma camera technique

    SciTech Connect

    Rehling, M.; Moller, M.L.; Jensen, J.J.; Thamdrup, B.; Lund, J.O.; Trap-Jensen, J.

    1986-01-01

    The reliability of a previously published method for determination of single kidney glomerular filtration rate (SKGFR) by means of technetium-99m-diethylenetriaminepenta-acetate (99mTc-DTPA) gamma camera renography was evaluated. The day-to-day variation in the calculated SKGFR values was earlier found to be 8.8%. The technique was compared to the simultaneously measured renal clearance of inulin in 19 unilaterally nephrectomized patients with GFR varying from 11 to 76 ml/min. The regression line (y = 1.04 X -2.5) did not differ significantly from the line of identity. The standard error of estimate was 4.3 ml/min. In 17 patients the inter- and intraobserver variation of the calculated SKGFR values was 1.2 ml/min and 1.3 ml/min, respectively. In 21 of 25 healthy subjects studied (age range 27-29 years), total GFR calculated from the renograms was within an established age-dependent normal range of GFR.

  17. The biodistribution and dosimetry of {sup 117m}Sn DTPA with special emphasis on active marrow absorbed doses

    SciTech Connect

    Stubbs, J.; Atkins, H.

    1999-01-01

    {sup 117m}Sn(4+) DTPA is a new radiopharmaceutical for the palliation of pain associated with metastatic bone cancer. Recently, the Phase 2 clinical trials involving 47 patients were completed. These patients received administered activities in the range 6.7--10.6 MBq/kg of body mass. Frequent collections of urine were acquired over the first several hours postadministration and daily cumulative collections were obtained for the next 4--10 days. Anterior/posterior gamma camera images were obtained frequently over the initial 10 days. Radiation dose estimates were calculated for 8 of these patients. Each patient`s biodistribution data were mathematically simulated using a multicompartmental model. The model consisted of the following compartments: central, bone, kidney, other tissues, and cumulative urine. The measured cumulative urine data were used as references for the cumulative urine excretion compartment. The total-body compartment (sum of the bone surfaces, central, kidney, and other tissues compartments) was reference to all activity not excreted in the urine.

  18. 99mTc-DTPA and 131I-Hippuran Findings in Liver Transplant Recipients Treated with Cyclosporin A

    PubMed Central

    Klintmalm, Göran B. G.; Klingensmith, William C.; Iwatsuki, Shunzaburo; Schröter, Gerhard P. J.; Starzl, Thomas E.

    2010-01-01

    The effects of cyclosporin A (CyA), an immunosuppressive agent that is potentially nephrotoxic, on the kidneys of 9 liver transplant recipients were studied with serial 99mTc-DTPA and 131I-hippuran scans. In addition, renal function was determined by measuring serum creatinine levels during the second postoperative week in the 9 unselected CyA-treated patients and, retrospectively, in a control group of 29 liver transplant recipients who had not been treated with CyA and who were selected because they had survived for at least 3 months postoperatively. The early postoperative creatinine level was significantly greater in the CyA group. Eight of the 9 CyA patients showed imaging abnormalities in all preoperative and postoperative studies. Five of the 8 patients showed a pattern similar to that of acute tubular necrosis (relatively preserved perfusion) in at least one study. Lowering the dosage of CyA permitted the continuation of therapy, and all 9 patients are alive after 8 to 14 months. PMID:7031760

  19. 99mTc-DTPA and /sup 131/I-hippuran findings in liver transplant recipients treated with cyclosporin A

    SciTech Connect

    Klintmalm, G.B.; Klingensmith, W.C.; Iwatsuki, S.; Schroeter, G.P.; Starzl, T.E.

    1982-01-01

    The effects of cyclosporin A (CyA), an immunosuppressive agent that is potentially nephrotoxic, on the kidneys of 9 liver transplant recipients were studied with serial 99mTc-DTPA and 131I-hippuran scans. In addition, renal function was determined by measuring serum creatinine levels during the second postoperative week in the 9 unselected CyA-treated patients and, retrospectively, in a control group of 29 liver transplant recipients who had not been treated with CyA and who were selected because they had survived for at least 3 months postoperatively. The early postoperative creatinine level was significantly greater in the CyA group. Eight of the 9 CyA patients showed imaging abnormalities in all preoperative and postoperative studies. Five of the 8 patients showed a pattern similar to that of acute tubular necrosis (relatively preserved perfusion) in at least one study. Lowering the dosage of CyA permitted the continuation of therapy, and all 9 patients are alive after 8 to 14 months.

  20. Registration of parametric dynamic F-18-FDG PET/CT breast images with parametric dynamic Gd-DTPA breast images

    NASA Astrophysics Data System (ADS)

    Magri, Alphonso; Krol, Andrzej; Lipson, Edward; Mandel, James; McGraw, Wendy; Lee, Wei; Tillapaugh-Fay, Gwen; Feiglin, David

    2009-02-01

    This study was undertaken to register 3D parametric breast images derived from Gd-DTPA MR and F-18-FDG PET/CT dynamic image series. Nonlinear curve fitting (Levenburg-Marquardt algorithm) based on realistic two-compartment models was performed voxel-by-voxel separately for MR (Brix) and PET (Patlak). PET dynamic series consists of 50 frames of 1-minute duration. Each consecutive PET image was nonrigidly registered to the first frame using a finite element method and fiducial skin markers. The 12 post-contrast MR images were nonrigidly registered to the precontrast frame using a free-form deformation (FFD) method. Parametric MR images were registered to parametric PET images via CT using FFD because the first PET time frame was acquired immediately after the CT image on a PET/CT scanner and is considered registered to the CT image. We conclude that nonrigid registration of PET and MR parametric images using CT data acquired during PET/CT scan and the FFD method resulted in their improved spatial coregistration. The success of this procedure was limited due to relatively large target registration error, TRE = 15.1+/-7.7 mm, as compared to spatial resolution of PET (6-7 mm), and swirling image artifacts created in MR parametric images by the FFD. Further refinement of nonrigid registration of PET and MR parametric images is necessary to enhance visualization and integration of complex diagnostic information provided by both modalities that will lead to improved diagnostic performance.

  1. [Assessment of obstructive nephropathy using diuretic 99mTc-DTPA renogram and 99mTc-DMSA renoscintigraphy].

    PubMed

    Okamura, K; Takaba, H; Ito, K; Shimoji, T

    1987-12-01

    99mTc-DMSA and diuretic 99mTc-DTPA renoscintigraphy were performed on 51 kidneys suspected of obstructive nephropathy based on excretory urography to evaluate the residual renal function and the degree of urinary flow impairment respectively. We classified the response to diuretics into 6 patterns: I. normal, IIa. severely damaged renal function, IIb. slow RI excretion without urinary tract visualization (pattern II had no response to furosemide), IIIa. rapid elimination of tracer from the obstructed upper tract, IIIb. slow elimination, and IV. gradual tracer accumulation in the pelvicalyceal system with fairly well preserved renal function but no response. Hydronephrosis varied according to pattern type, in the ascending order of I, IIIa, IIIb and IV (p less than 0.05). Degree of hydronephrosis was inversely related to 99mTc-DMSA uptake, but without statistical significance. 99mTc-DMSA uptake was lower for pattern III as a whole (IIIa + (IIIb) than for pattern I (p less than 0.005), but there was no difference between IIIa and IIIb. Pattern IIa exhibited a significantly lower uptake than any of the other groups. (p less than 0.005) In contrast to previous views, we believe that pattern IIIa indicates a mild obstruction of urinary flow and impaired renal function. Consequently, assessment of obstructive nephropathy should not be based only on urodynamic study but also on differential renal function test.

  2. Interpretation of Urinary Excretion Data From Plutonium Wound Cases Treated With DTPA: Application of Different Models and Approaches.

    PubMed

    Poudel, Deepesh; Bertelli, Luiz; Klumpp, John A; Waters, Tom L

    2017-07-01

    After a chelation treatment, assessment of intake and doses is the primary concern of an internal dosimetrist. Using the urinary excretion data from two actual wound cases encountered at Los Alamos National Laboratory (LANL), this paper discusses several methods that can be used to interpret intakes from the urinary data collected after one or multiple chelation treatments. One of the methods uses only the data assumed to be unaffected by chelation (data collected beyond 100 d after the last treatment). This method, used by many facilities for official dose records, was implemented by employing maximum likelihood analysis and Bayesian analysis methods. The impacts of an improper assumption about the physicochemical behavior of a radioactive material and the importance of the use of a facility-specific biokinetic model when available have also been demonstrated. Another method analyzed both the affected and unaffected urinary data using an empirical urinary excretion model. This method, although case-specific, was useful in determining the actual intakes and the doses averted or the reduction in body burdens due to chelation treatments. This approach was important in determining the enhancement factors, the behavior of the chelate, and other observations that may be pertinent to several DTPA compartmental modeling approaches being conducted by the health physics community.

  3. Sucralose sweetener in vivo effects on blood constituents radiolabeling, red blood cell morphology and radiopharmaceutical biodistribution in rats.

    PubMed

    Rocha, G S; Pereira, M O; Benarroz, M O; Frydman, J N G; Rocha, V C; Pereira, M J; Fonseca, A S; Medeiros, A C; Bernardo-Filho, M

    2011-01-01

    Effects of sucralose sweetener on blood constituents labelled with technetium-99m ((99m)Tc) on red blood cell (RBC) morphology, sodium pertechnetate (Na(99m)TcO(4)) and diethylenetriaminepentaacetic acid labeled with (99m)Tc ((99m)Tc-DTPA) biodistribution in rats were evaluated. Radiolabeling on blood constituents from Wistar rats was undertaken for determining the activity percentage (%ATI) on blood constituents. RBC morphology was also evaluated. Na(99m)TcO(4) and (99m)Tc-DTPA biodistribution was used to determine %ATI/g in organs. There was no alteration on RBC blood constituents and morphology %ATI. Sucralose sweetener was capable of altering %ATI/g of the radiopharmaceuticals in different organs. These findings are associated to the sucralose sweetener in specific organs.

  4. Renal scans in pregnant transplant patients

    SciTech Connect

    Goldstein, H.A.; Ziessman, H.A.; Fahey, F.H.; Collea, J.V.; Alijani, M.R.; Helfrich, G.B.

    1988-08-01

    This study demonstrates the normal technetium-99m diethylenetriaminepentaacetic acid ((/sup 99m/Tc)DTPA) renal scan in pregnant patients with transplanted kidneys. Five pregnant renal transplant patients had seven (/sup 99m/Tc)DTPA renal studies to assess allograft perfusion and function. All scans showed the uteroplacental complex. The bladder was always compressed and distorted. The transplanted kidney was frequently rotated to a more vertical position. In all patients allograft flow and function were maintained. There was calyceal retention on all studies and ureteral retention activity in three of five patients. Using the MIRD formalism, the total radiation absorbed dose to the fetus was calculated to be 271 mrad. This radiation exposure is well within NRCP limits for the fetus of radiation workers and an acceptable low risk in the management of these high risk obstetric patients.

  5. New approaches to the design and synthesis of protein-based radiopharmaceuticals with application to the radiolabelling of antibodies

    SciTech Connect

    Layne, W.W.

    1985-01-01

    A new method of radiolabeling proteins has been explored that involves the coupling of a metal chelating agent, diethylenetriaminepentaacetic acid (DTPA), to proteins in aqueous solution through the use of the DTPA bisanhydride. Each derivatized protein was then radiolabeled with an appropriate carrier-free metallic radionuclide. The proteins examined in this investigation were human serum albumin, human and canine fibrinogen, bovine and human nonspecific gamma globulin, and antibodies to carcinoembryonic antigen (CEA). The two different anti-CEA antibodies chosen for this study were affinity-purified baboon anti-human CEA and monoclonal murine anti-human CEA. The radionuclides were gallium-67, indium-111, and yttrium-90. With /sup 111/In, the method was shown to successfully radiolabel each of the model proteins without significantly altering their in vitro or in vivo behavior.

  6. Tumor characterization in small animals using magnetic resonance-guided dynamic contrast enhanced diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Lin, Yuting; Thayer, Dave; Nalcioglu, Orhan; Gulsen, Gultekin

    2011-10-01

    We present a magnetic resonance (MR)-guided near-infrared dynamic contrast enhanced diffuse optical tomography (DCE-DOT) system for characterization of tumors using an optical contrast agent (ICG) and a MR contrast agent [Gd-diethylenetriaminepentaacetic acid (DTPA)] in a rat model. Both ICG and Gd-DTPA are injected and monitored simultaneously using a combined MRI-DOT system, resulting in accurate co-registration between two imaging modalities. Fisher rats bearing R3230 breast tumor are imaged using this hybrid system. For the first time, enhancement kinetics of the exogenous contrast ICG is recovered from the DCE-DOT data using MR anatomical a priori information. As tumors grow, they undergo necrosis and the tissue transforms from viable to necrotic. The results show that the physiological changes between viable and necrotic tissue can be differentiated more accurately based on the ICG enhancement kinetics when MR anatomical information is utilized.

  7. Extraction and determination of hexavalent chromium in soil samples.

    PubMed

    Grabarczyk, Malgorzata; Korolczuk, Mieczyslaw; Tyszczuk, Katarzyna

    2006-09-01

    A procedure for the extraction of Cr(VI) from solid soil-like samples was presented in which the complexing properties of diethylenetriaminepentaacetic acid (DTPA) were exploited to extract insoluble compounds of Cr(VI). A concentration of DTPA in an ammonium sulphate/ammonium hydroxide buffer equal to 0.02 mol l(-1) was chosen. The conditions of extraction of insoluble Cr(VI) from solid samples were optimised using soil certified reference material spiked with known concentration of insoluble Cr(VI) added as PbCrO(4). The extracts were analysed by adsorptive stripping voltammetry. Validation of the proposed procedure of extraction was carried out by analysis of certified reference material (CRM) 545 and comparison of the results obtained using the proposed and other methods of extraction in the course of analysis of natural soil samples.

  8. Magnetic separation - Advanced nanotechnology for future nuclear fuel recycle

    SciTech Connect

    Kaur, M.; Zhang, H.; Qiang, Y.; Martin, L.; Todd, T.

    2013-07-01

    The unique properties of magnetic nanoparticles (MNPs), such as their extremely small size and high surface area to volume ratio, provide better kinetics for the adsorption of metal ions from aqueous solutions. In this work, we demonstrated the separation of minor actinides using complex conjugates of MNPs with diethylenetriamine-pentaacetic acid (DTPA) chelator. The sorption results show the strong affinity of DTPA towards Am (III) and Pu (IV) by extracting 97% and 80% of actinides, respectively. It is shown that the extraction process is highly dependent on the pH of the solution. If these long-term heat generating actinides can be efficiently removed from the used fuel raffinates, the volume of material that can be placed in a given amount of repository space can be significantly increased. (authors)

  9. NIH/NIAID Radiation/Nuclear Medical Countermeasures Development Program

    DTIC Science & Technology

    2011-06-15

    Medical Countermeasure Development – NIAID Omnibus ■Contracts –Oral Forms of DTPA (2) –RERF –Product Development Support Services ■Inter/intra Agency...radionuclides  Contract and Grant Programs - Oral Form of Diethylenetriaminepentaacetate ( DTPA ) - Oral Radionuclide Decorporation Agents Biodosimetry

  10. Treatment of Peritoneal Carcinomatosis by Targeted Delivery of the Radio-Labeled Tumor Homing Peptide 213Bi-DTPA-[F3]2 into the Nucleus of Tumor Cells

    PubMed Central

    Miederer, Matthias; Blechert, Birgit; Vallon, Mario; Müller, Jan M.; Alke, Andrea; Seidl, Christof; Bruchertseifer, Frank; Morgenstern, Alfred; Senekowitsch-Schmidtke, Reingard; Essler, Markus

    2009-01-01

    Background α-particle emitting isotopes are effective novel tools in cancer therapy, but targeted delivery into tumors is a prerequisite of their application to avoid toxic side effects. Peritoneal carcinomatosis is a widespread dissemination of tumors throughout the peritoneal cavity. As peritoneal carcinomatosis is fatal in most cases, novel therapies are needed. F3 is a tumor homing peptide which is internalized into the nucleus of tumor cells upon binding to nucleolin on the cell surface. Therefore, F3 may be an appropriate carrier for α-particle emitting isotopes facilitating selective tumor therapies. Principal Findings A dimer of the vascular tumor homing peptide F3 was chemically coupled to the α-emitter 213Bi (213Bi-DTPA-[F3]2). We found 213Bi-DTPA-[F3]2 to accumulate in the nucleus of tumor cells in vitro and in intraperitoneally growing tumors in vivo. To study the anti-tumor activity of 213Bi-DTPA-[F3]2 we treated mice bearing intraperitoneally growing xenograft tumors with 213Bi-DTPA-[F3]2. In a tumor prevention study between the days 4–14 after inoculation of tumor cells 6×1.85 MBq (50 µCi) of 213Bi-DTPA-[F3]2 were injected. In a tumor reduction study between the days 16–26 after inoculation of tumor cells 6×1.85 MBq of 213Bi-DTPA-[F3]2 were injected. The survival time of the animals was increased from 51 to 93.5 days in the prevention study and from 57 days to 78 days in the tumor reduction study. No toxicity of the treatment was observed. In bio-distribution studies we found 213Bi-DTPA-[F3]2 to accumulate in tumors but only low activities were found in control organs except for the kidneys, where 213Bi-DTPA-[F3]2 is found due to renal excretion. Conclusions/Significance In conclusion we report that 213Bi-DTPA-[F3]2 is a novel tool for the targeted delivery of α-emitters into the nucleus of tumor cells that effectively controls peritoneal carcinomatosis in preclinical models and may also be useful in oncology. PMID:19479088

  11. ErbB-2 blockade and prenyltransferase inhibition alter epidermal growth factor and epidermal growth factor receptor trafficking and enhance (111)In-DTPA-hEGF Auger electron radiation therapy.

    PubMed

    Cornelissen, Bart; Darbar, Sonali; Hernandez, Rebecca; Kersemans, Veerle; Tullis, Iain; Barber, Paul R; Smart, Sean; Vojnovic, Borivoj; Reilly, Raymond; Vallis, Katherine A

    2011-05-01

    The intracellular distribution of Auger electron-emitting radiopharmaceuticals is a determinant of cytotoxicity. However, the mechanisms by which these agents are routed through the cell are ill understood. The aim of this study was to investigate how trafficking of (111)In-labeled human epidermal growth factor ((111)In-DTPA-hEGF) relates to that of the EGF receptor (EGFR) and whether coadministration of agents that modulate EGFR signaling alters the efficacy of (111)In-DTPA-hEGF. The spatiotemporal interaction between AlexaFluor488-EGF (AF488-EGF) and Cy3-conjugated anti-EGFR antibody (Cy3-anti-EGFR) was studied in the breast cancer cell line MDA-MB-468 using fluorescence resonance energy transfer and 2-photon fluorescence lifetime imaging. (111)In internalization and nuclear fractionation assays were performed to investigate the effect of the ErbB-2-blocking antibody trastuzumab and a prenyltransferase inhibitor, L-778,123, on the subcellular localization of (111)In-DTPA-hEGF in MDA-MB-468 (1.3 × 10(6) EGFR per cell; ErbB-2 negative) and 231-H2N (0.2 × 10(6) EGFR per cell; 0.4 × 10(5) ErbB-2 per cell) cell lines. The cytotoxicity of (111)In-DTPA-hEGF (0-64 nM) plus trastuzumab (0-50 μg/mL) or L-778,123 (0-22.5 μM) was measured using clonogenic assays in a panel of breast cancer cell lines that express different levels of EGFR and ErB-2. Clonogenic survival data were used to calculate combination indices. Tumor growth inhibition was measured in vivo in 231-H2N xenograft-bearing mice treated with (111)In-DTPA-hEGF plus trastuzumab or L-788,123. Using fluorescence resonance energy transfer, we showed that EGF interacts with EGFR in the cytoplasm and nucleus after internalization of the ligand-receptor complex in MDA-MB-468 cells. Nuclear localization of (111)In-DTPA-hEGF is enhanced by trastuzumab and L-788,123. Trastuzumab and L-788,123 sensitized 231-H2N cells to (111)In-DTPA-hEGF. Nuclear localization and cytotoxicity of (111)In-DTPA-hEGF were significantly

  12. Using DTPA-extractable soil fraction to assess the bioconcentration factor of plants in phytoremediation of urban soils

    NASA Astrophysics Data System (ADS)

    Rodríguez-Bocanegra, Javier; Roca, Núria; Tume, Pedro; Bech, Jaume

    2017-04-01

    carbon content are generally considered the most important factors when evaluating the heavy metal content of soils. Therefore, it could be essential to find a soil extractant with the capacity of isolate and extract heavy metals from this soil phase. The extraction methods, e.g. DTPA, have been widely and successfully applied in the study of nutrients elements deficiency in agricultural crops. These extraction methods could be some excellent methods of assessment of potential bioaccumulation capacity of phytoremediation plants in polluted cases. BF-DTPA FRACTION index was >1 in all plants that grew in the urban soil from Talcahuano (Chile), and in too many cases, it was >1 in soil from Sants district (Spain). However, these values were slightly <1 using BF-TOTAL FRACTION index. Thus, so many plants would be being considered non hyperaccumulator plants when the reality is that these plants are uptaking hazardous trace elements in significant quantities. The bioavailable fraction should be considered to define bioconcentration factor as the fraction to assess the potential likelihood of heavy metal mobility and availability with all the implications for toxicity problems.

  13. Accurate and precise plasma clearance measurement using four 99mTc-DTPA plasma samples over 4 h

    PubMed Central

    Wanasundara, Surajith N.; Wesolowski, Michal J.; Barnfield, Mark C.; Waller, Michael L.; Murray, Anthony W.; Burniston, Maria T.; Babyn, Paul S.

    2016-01-01

    Objectives Glomerular filtration rate can be measured as the plasma clearance (CL) of a glomerular filtration rate marker despite body fluid disturbances using numerous, prolonged time samples. We desire a simplified technique without compromised accuracy and precision. Materials and methods We compared CL values derived from two plasma concentration curve area methods – (a) biexponential fitting [CL (E2)] and (b) Tikhonov adaptively regularized gamma variate fitting [CL (Tk-GV)] – for 4 versus 8 h time samplings from 412 99mTc-DTPA studies in 142 patients, mostly paediatric patients, with suspected fluid disturbances. Results CL (Tk-GV) from four samples/4 h and from nine samples/8 h, both accurately and precisely agreed with the standard, which was taken to be nine samples/8 h CL from (noncompartmental) numerical integration [CL (NI)]. The E2 method, four samples/4 h, and nine samples/8 h median CL values significantly overestimated the CL (NI) values by 4.9 and 3.8%, respectively. Conclusion Compared with the standard, CL (E2) from four samples/4 h and from nine samples/8 h proved to be the most inaccurate and imprecise method examined, and can be replaced by better methods for calculating CL. The CL (Tk-GV) can be used to reduce sampling time in half from 8 to 4 h and from nine to four samples for a precise and accurate, yet more easily tolerated and simplified test. PMID:26465802

  14. Estimating glomerular filtration rate in oncology patients receiving Cisplatin chemotherapy: Predicted creatinine clearance against 99mTc-DTPA methods

    NASA Astrophysics Data System (ADS)

    Khaidah Syed Sahab, Sharifah; Manap, Mahayuddin; Hamzah, Fadzilah

    2017-05-01

    The therapeutic potential of cisplatin as the best anticancer treatment for solid tumor is limited by its potential nephrotoxicity. This study analyses the incidence of cisplatin induced nephrotoxicity in oncology patients through GFR estimation using 99mTc-DTPA plasma sampling (reference method) and to compare with predicted creatinine clearance and Tc-99m renal scintigraphy. A prospective study of 33 oncology patients referred for GFR estimation in Penang Hospital. The incidence of cisplatin induced nephrotoxicity was analysed via radionuclide and creatinine based method. Of 33 samples, only 21 selected for the study. The dose of cisplatin given was 75 mg/m2 for each cycle. The mean difference of GFR pre and post chemotherapy (PSC 2) was 13.38 (-4.60, 31.36) ml/min/1.73m2 (p 0.136). Of 21 patients, 3 developed severe nephrotoxicity (GFR < 50ml/min/1.73 m2) contributing 14.3% of incidence. Bland-Altman plot showed only PSC 1 is in agreement with PSC 2 technique. Intraclass Correlation Coefficients (ICC) also showed that PSC 1 has high degree of reliability in comparison to PSC 2 (p < 0.001). The other methods do not show reliability and agreement in comparison to PSC 2 (p < 0.05). 3 of 21 patients (14.3%) developed severe nephrotoxicity post cisplatin chemotherapy. This percentage is much less than the reported 20 - 25% of cases from other studies, probably due to small sample size and biased study population due to strict exclusion criteria. Radionuclide method for evaluating GFR is the most sensitive method for the detection of cisplatin induced nephrotoxicity by showing 3 of 21 patients developing severe nephrotoxicity. PSC 1 was found to be a reliable substitute of PSC 2. The other methods are not reliable for detection of early nephrotoxicity. We will recommend the use of single plasma sampling method (PSC 1) for GFR estimation in monitoring post cisplatin chemotherapy patients.

  15. Semi-automatic detection of Gd-DTPA-saline filled capsules for colonic transit time assessment in MRI

    NASA Astrophysics Data System (ADS)

    Harrer, Christian; Kirchhoff, Sonja; Keil, Andreas; Kirchhoff, Chlodwig; Mussack, Thomas; Lienemann, Andreas; Reiser, Maximilian; Navab, Nassir

    2008-03-01

    Functional gastrointestinal disorders result in a significant number of consultations in primary care facilities. Chronic constipation and diarrhea are regarded as two of the most common diseases affecting between 2% and 27% of the population in western countries 1-3. Defecatory disorders are most commonly due to dysfunction of the pelvic floor or the anal sphincter. Although an exact differentiation of these pathologies is essential for adequate therapy, diagnosis is still only based on a clinical evaluation1. Regarding quantification of constipation only the ingestion of radio-opaque markers or radioactive isotopes and the consecutive assessment of colonic transit time using X-ray or scintigraphy, respectively, has been feasible in clinical settings 4-8. However, these approaches have several drawbacks such as involving rather inconvenient, time consuming examinations and exposing the patient to ionizing radiation. Therefore, conventional assessment of colonic transit time has not been widely used. Most recently a new technique for the assessment of colonic transit time using MRI and MR-contrast media filled capsules has been introduced 9. However, due to numerous examination dates per patient and corresponding datasets with many images, the evaluation of the image data is relatively time-consuming. The aim of our study was to develop a computer tool to facilitate the detection of the capsules in MRI datasets and thus to shorten the evaluation time. We present a semi-automatic tool which provides an intensity, size 10, and shape-based 11,12 detection of ingested Gd-DTPA-saline filled capsules. After an automatic pre-classification, radiologists may easily correct the results using the application-specific user interface, therefore decreasing the evaluation time significantly.

  16. Nonaqueous gel for the transdermal delivery of a DTPA penta-ethyl ester prodrug.

    PubMed

    Zhang, Yong; Sadgrove, Matthew P; Sueda, Katsuhiko; Yang, Yu-Tsai; Pacyniak, Erik K; Kagel, John R; Braun, Brenda A; Zamboni, William C; Mumper, Russell J; Jay, Michael

    2013-04-01

    Diethylenetriamine pentaacetic acid penta-ethyl ester, designated as C2E5, was successfully incorporated into a nonaqueous gel for transdermal delivery. The thermal and rheological properties of a formulation containing 40% C2E5, 20% ethyl cellulose, and 40% Miglyol 840® prepared using the solvent evaporation method demonstrated that the gel had acceptable content uniformity and flow properties. In vitro studies showed that C2E5 was steadily released from the gel at a rate suitable for transdermal delivery. Topical application of the gel at a 200 mg C2E5/kg dose level in rats achieved significantly higher plasma exposures of several active metabolites compared with neat C2E5 oil at the same dose level. The results suggest that transdermal delivery of a chelator prodrug is an effective radionuclide decorporation strategy by delivering chelators to the circulation with a pharmacokinetic profile that is more consistent with the biokinetic profile of transuranic elements in contaminated individuals.

  17. Periportal lymphatic system on post-hepatobiliary phase Gd-EOB-DTPA-enhanced MR imaging in normal subjects and patients with chronic hepatitis C.

    PubMed

    Yamada, Yasunari; Matsumoto, Shunro; Mori, Hiromu; Takaji, Ryo; Kiyonaga, Maki; Hijiya, Naoki; Tanoue, Rika; Tomonari, Kenichiro; Tanoue, Shuichi; Hongo, Norio; Ohta, Masayuki; Seike, Masataka; Inomata, Masafumi; Murakami, Kazunari; Moriyama, Masatsugu

    2017-04-25

    We sought to evaluate visualization of periportal lymphatics and lymph nodes (lymphatic system) on Gd-EOB-DTPA-enhanced magnetic resonance (MR) images using a fat-suppressed T2-weighted sequence with 3-dimensional (3D) volume isotropic turbo spin echo acquisition (VISTA) at 3.0 T in normal subjects and patients with chronic hepatitis C. MR imaging was performed in 254 subjects between June 2013 and May 2016. After applying inclusion and exclusion criteria, the final population was 31 normal subjects and 34 patients with chronic hepatitis C. Images were acquired after the hepatobiliary phase following intravenous administration of Gd-EOB-DTPA, which causes signal loss in the bile ducts, to facilitate the visualization of the periportal lymphatic system. Two radiologists assessed the visualization of the periportal lymphatic system in 31 normal subjects. The axial dimensions of the main periportal lymphatic system in normal subjects were measured and compared with those of 34 patients with chronic hepatitis C using the Mann-Whitney U-test, and their correlation with a hepatic fibrosis marker, the Fibrosis-4 (FIB-4), was assessed using Spearman's rank correlation test. The periportal lymphatic system was detected as high signal intensity areas surrounding the portal vein up to the third branches by each reader in all normal subjects. The axial dimensions of the main periportal lymphatic system in patients with chronic hepatitis C were significantly larger than those in normal subjects (p < 0.0001), and showed a significantly positive correlation with the FIB-4 score (ρ = 0.73, p < 0.001). Fat-suppressed T2-weighted MR imaging with 3D-VISTA acquired after the hepatobiliary phase on Gd-EOB-DTPA-enhanced imaging may be a useful noninvasive method for evaluating the periportal lymphatic system and the degree of hepatic fibrosis.

  18. Comparison of 10- and 20-min hepatobiliary phase images on Gd-EOB-DTPA-enhanced MRI T1 mapping for liver function assessment in clinic.

    PubMed

    Zhou, Zhi-Peng; Long, Li-Ling; Qiu, Wei-Jia; Cheng, Ge; Huang, Li-Juan; Yang, Teng-Fei; Huang, Zhong-Kui

    2017-04-10

    To compare hepatobiliary phase (HBP) images obtained 10 and 20 min after Gd-EOB-DTPA-enhanced MRI for liver function assessment in clinic on 3.0 T MR imaging. 103 patients were separated into four groups: 38 patients for the normal liver function (NLF) group, 33 patients for the liver cirrhosis with Child-Pugh A (LCA) group, 21 patients for the liver cirrhosis with Child-Pugh B group, and 11 patients for a liver cirrhosis with Child-Pugh C group. T1 relaxation times (T1rt) were measured on T1 mapping and reduction rates of T1rt (rrT1rt) were calculated. HBP images were obtained at the 10- and 20-min mark after Gd-EOB-DTPA enhancement. T1rt on pre-enhancement imaging showed no significant difference (p > 0.05) among all four groups. T1rt for both the 10-min HBP and the 20-min HBP showed a significant difference (p < 0.05) among all groups, but showed no significant difference (p > 0.05) between the NLF group and the LCA group. T1rt and rrT1rt showed no significant difference (p > 0.05) between 10-min HBP and 20-min HBP among all groups. The ROC analysis on 10-min HBP and 20-min HBP showed a lower diagnostic performance between NLF group and LCA group (AUC from 0.532 to 0.582), but high diagnostic performance (AUC from 0.788 to 1.000) among others group. In comparing 10-min HBP and 20-min HBP T1 mapping after Gd-EOB-DTPA enhancement, our results suggest that 10-min HBP T1 mapping is a feasible option for quantitatively assessing liver function.

  19. Evaluation of in vivo targeting of andenocarcinomas with In-111-DTPA-B72.3-antibody under treatment with interferon gamma

    SciTech Connect

    Becherer, A.; Raderer, M.; Scheithauer, W.

    1994-05-01

    The monoclonal antibody (mAb) In-111-DTPA-B72.3 directed against the tumor-associated glycoprotein (TAG)-72 has successfully been used for tumor diagnosis and staging, however, for evaluation of liver metastases the sensitivity is poor. Interferon gamma (IFNg) has been reported to increase TAG-72 expression on ascites tumor cells in patients with gastrointestinal adenocarcinomas. This study was undertaken to show a possible influence of IFNg on the diagnostic abilities of imunnoscintigraphy with In-111-DTPA-B72.3. We compared the in vivo targeting in 12 patients (9 males, 3 females, 59{plus_minus}16 years) under IFNg treatment (250 g daily s.c.) with a control group of 17 patients (10 males, 7 females, 66{plus_minus}10 years). In 5 patients (3 males, 2 females, 65{plus_minus}13 years) repeated scanning was performed before and during IFNg treatment. The patients suffered from advanced colorectal, pancreatic or gastric adenocarcinomas and underwent surgery and chemotherapy prior to scintigraphic investigations. In patients without IFNg, primary resp. residual tumors were imaged in 1 of 5 and liver metastases in 9 of 14 patients. In the IFNg-treated patients primary resp. residual tumors were visualized in 1 of 3 and Ever metastases in 8 of 9 patients (89%, vs 64% control group). Contrast of imaging for liver metastases was improved in 2 of 5 patients under treatment with IFNg while no difference in the visualization of primary resp. residual tumors could be realized under IFNg treatment. We conclude that in vivo targeting of TAG-72 with In-111-DTPA-B72.3 mAb may be increased in tumor patients under therapy with IFNg.

  20. Detection of hepatocellular carcinoma by Gd-EOB-DTPA-enhanced liver MRI: comparison with triple phase 64 detector row helical CT.

    PubMed

    Akai, Hiroyuki; Kiryu, Shigeru; Matsuda, Izuru; Satou, Jirou; Takao, Hidemasa; Tajima, Taku; Watanabe, Yasushi; Imamura, Hiroshi; Kokudo, Norihiro; Akahane, Masaaki; Ohtomo, Kuni

    2011-11-01

    To compare the diagnostic performance of Gd-EOB-DTPA-enhanced MRI with that of triple phase 64-MDCT in the detection of hepatocellular carcinoma (HCC). Thirty-four patients with 52 surgically proven lesions underwent Gd-EOB-DTPA-enhanced MRI and triple phase 64-MDCT. Two observers independently evaluated MR and CT imaging on a lesion-by-lesion basis. Sensitivity, positive and negative predictive values and reproducibility were evaluated. The diagnostic accuracy of each modality was assessed with alternative-free response receiver operating characteristic (ROC) analysis. Both observers showed higher sensitivity in detecting lesions with MRI compared to CT, however, only the difference between the two imaging techniques for observer 2 was significant (P=0.034). For lesions 1cm or smaller, MRI and CT showed equal sensitivity (both 62.5%) with one observer, and MRI proved superior to CT with the other observer (MRI 75% vs. CT 56.3%), but the latter difference was not significant (P=0.083). The difference in positive and negative predictive value between the two imaging techniques for each observer was not significant (P>0.05). The areas under the ROC curve for each observer were 0.843 and 0.861 for MRI vs. 0.800 and 0.833 for CT and the differences were not significant. Reproducibility was higher using MRI for both observers, but the result was not significant (MRI 32/33 vs. CT 29/33, P=0.083). Gd-EOB-DTPA-enhanced MRI tended to show higher diagnostic accuracy, sensitivity and reproducibility compared to triple phase 64-MDCT in the detection of hepatocellular carcinoma, however statistical significance was not achieved. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Detection and characterisation of focal liver lesions in colorectal carcinoma patients: comparison of diffusion-weighted and Gd-EOB-DTPA enhanced MR imaging.

    PubMed

    Löwenthal, D; Zeile, M; Lim, W Y; Wybranski, C; Fischbach, F; Wieners, G; Pech, M; Kropf, S; Ricke, J; Dudeck, O

    2011-04-01

    To compare diffusion-weighted imaging (DWI) and Gd-EOB-DTPA-enhanced magnetic resonance (MR) imaging for the detection and characterisation of focal liver lesions (FLLs) in patients with colorectal carcinoma. Seventy-three patients underwent MR imaging including echoplanar DWI (MR-DWI) and dynamic (MR-Dyn) and hepatobiliary phase (MR-Late) Gd-EOB-DTPA-enhanced images. Two blinded readers independently reviewed 5 different image sets using a 5-point confidence scale. Accuracy was assessed by the area (A(z)) under the receiver operating characteristic curve, and sensitivity and specificity were calculated. A total of 332 FLLs were evaluated. Detection rates were significantly higher for MR-Late images (94.4% for benign and 100% for malignant lesions) compared with MR-DWI (78.3% and 97.5%) and MR-Dyn images (81.5% and 89.9%). Accuracy was 0.82, 0.76 and 0.89 for MR-DWI, MR-Dyn and MR-Late images while sensitivity was 0.98, 0.87 and 0.95, respectively. For characterisation of subcentimetre lesions sensitivity was highest for MR-DWI (0.92). Combined reading of unenhanced and contrast-enhanced images had an identical high accuracy of 0.98. Late-phase Gd-EOB-DTPA-enhanced images were superior for the detection of FLLs, while DWIs were most valuable for the identification of particularly small metastases. Combined interpretation of unenhanced images resulted in precise characterisation of FLLs.

  2. Risk of hypervascularization in small hypovascular hepatic nodules showing hypointense in the hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with chronic liver disease.

    PubMed

    Takechi, Megumi; Tsuda, Takaharu; Yoshioka, Shinji; Murata, Shigetoshi; Tanaka, Hiroaki; Hirooka, Masashi; Mochizuki, Teruhito

    2012-11-01

    The purpose of this study was to elucidate the incidence and risk factors for the progression of hypointense nodules observed in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) of hypervascular hepatocellular carcinoma (HCC). Hypovascular nodules (112) showing hypointensity in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were examined in 54 patients. All patients underwent computed tomography during hepatic arteriography and computed tomography during arterial portography (CTAP) within a month after Gd-EOB-DTPA-enhanced MRI. According to the tumor size, 112 nodules were divided into two groups: those >10 mm in diameter (group A, n = 39) and those ≤10 mm in diameter (group B, n = 73). The incidence of progression to hypervascular HCC was calculated using the Kaplan-Meier method. The incidence of hypervascularization was significantly higher in group A nodules than in group B nodules (p < 0.0001). Tumor size (p < 0.0001) and hypoattenuation in CTAP (p = 0.0004) showed significant correlation with hypervascularization. Hypointense nodules observed in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI with diameters of >10 mm had a high probability of hypervascularization.

  3. A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI

    NASA Astrophysics Data System (ADS)

    Russo, Maria; Bevilacqua, Paolo; Netti, Paolo Antonio; Torino, Enza

    2016-11-01

    Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications.

  4. A Microfluidic Platform to design crosslinked Hyaluronic Acid Nanoparticles (cHANPs) for enhanced MRI

    PubMed Central

    Russo, Maria; Bevilacqua, Paolo; Netti, Paolo Antonio; Torino, Enza

    2016-01-01

    Recent advancements in imaging diagnostics have focused on the use of nanostructures that entrap Magnetic Resonance Imaging (MRI) Contrast Agents (CAs), without the need to chemically modify the clinically approved compounds. Nevertheless, the exploitation of microfluidic platforms for their controlled and continuous production is still missing. Here, a microfluidic platform is used to synthesize crosslinked Hyaluronic Acid NanoParticles (cHANPs) in which a clinically relevant MRI-CAs, gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA), is entrapped. This microfluidic process facilitates a high degree of control over particle synthesis, enabling the production of monodisperse particles as small as 35 nm. Furthermore, the interference of Gd-DTPA during polymer precipitation is overcome by finely tuning process parameters and leveraging the use of hydrophilic-lipophilic balance (HLB) of surfactants and pH conditions. For both production strategies proposed to design Gd-loaded cHANPs, a boosting of the relaxation rate T1 is observed since a T1 of 1562 is achieved with a 10 μM of Gd-loaded cHANPs while a similar value is reached with 100 μM of the relevant clinical Gd-DTPA in solution. The advanced microfluidic platform to synthesize intravascularly-injectable and completely biocompatible hydrogel nanoparticles entrapping clinically approved CAs enables the implementation of straightforward and scalable strategies in diagnostics and therapy applications. PMID:27901092

  5. Occurrence of aminopolycarboxylates in the aquatic environment of Germany.

    PubMed

    Schmidt, Carsten K; Fleig, Michael; Sacher, Frank; Brauch, Heinz-Jürgen

    2004-09-01

    Aminopolycarboxylic acids, such as ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), diethylenetriaminepentaacetic acid (DTPA), 1,3-propylenediaminetetraacetic acid (1,3-PDTA), beta-alaninediacetic acid (beta-ADA), and methylglycinediacetic acid (MGDA), are used in large quantities in a broad range of industrial applications and domestic products in order to solubilize or inactivate various metal ions by complex formation. Due to the wide field of their application, their high polarity and partly low degradability, these substances reach the aquatic environment at considerable concentrations (in the microg/L-range) and have also been detected in drinking water. This review evaluates and summarizes the results of long-term research projects, monitoring programs, and published papers concerning the pollution of the aquatic environment by aminopolycarboxylates in Germany. Concentrations and loads of aminopolycarboxylates are presented for various types of water including industrial and domestic waste waters, surface waters (rivers and lakes), raw waters, and drinking waters.

  6. Comparison of 111In-[DTPA0]Octreotide Versus Non Carrier Added 177Lu- [DOTA0,Tyr3]-Octreotate Efficacy in Patients With GEP-NET Treated Intra-arterially for Liver Metastases.

    PubMed

    Limouris, G S; Poulantzas, V; Trompoukis, N; Karfis, I; Chondrogiannis, S; Triantafyllou, N; Gennimata, V; Moulopoulou, L-E; Patsouris, E; Nikou, G; Michalaki, V; Fragulidis, G; Paphiti, M; McCready, R V; Colletti, P M; Cook, G J; Rubello, D

    2016-03-01

    In patients with progressive, metastatic neuroendocrine tumors (NET), intra-arterial radionuclide infusions with high activities of In-[DTPA]-octreotide and more recently with non-carrier added (nca) Lu-[DOTA,Tyr]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (In-[DTPA]-octreotide, 22 ± 3.6 nM and nca Lu-[DOTA,Tyr]-octreotate, 1.5 ± 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs. Thirty patients with gastroenteropancreatic (GEP) somatostatin-positive NETs with liver metastases confirmed on biopsy and In-pentetreotide scan were included. They were treated with In-[DTPA]-octreotide (n = 17) or nca Lu-[DOTA,Tyr]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/ 1.0 software. ncaLu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than In-[DTPA]-octreotide (P < 0.05), as clearly depicted from the time-activity curves; the background-corrected tumor uptake was significantly higher than In-[DTPA]-octreotide but without any significant difference in other organs (spleen, kidneys, and liver). Using Lu-[DOTA,Tyr]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with In-[DTPA] octreotide. Residence time of nca Lu-[DOTA,Tyr]-octreotate results in a significantly higher absorbed dose to bone marrow compared with In-[DTPA]-octreotide. However, a drawback of In-[DTPA]-octreotide therapy is that the number of administrations would need to be

  7. Direct lung delivery of a dry powder formulation of DTPA with improved aerosolization properties: effect on lung and systemic decorporation of plutonium.

    PubMed

    Gervelas, C; Serandour, A-L; Geiger, S; Grillon, G; Fritsch, P; Taulelle, C; Le Gall, B; Benech, H; Deverre, J-R; Fattal, E; Tsapis, N

    2007-03-12

    DTPA, an actinide chelating agent, has demonstrated its ability to complex plutonium (Pu) and to facilitate its urinary excretion after internal contamination. This process, known as decorporation is crucial to diminish the burden of Pu in the body. The ability to deliver a chelating agent directly to the alveolar region may increase its local concentration as compared to systemic delivery and therefore increase the extent of decorporation. Second, inhalation offers the potential for needle-free, systemic delivery of small molecules and would be convenient in case of nuclear accident as a first pass emergency treatment. To benefit from the improvement of inhalation technology, we have formulated DTPA into porous particles by spray-drying with dl-Leucine, DPPC and ammonium bicarbonate. The optimized particles possess a volume mean geometric diameter around 4.5 mum and crumpled paper morphology. The in vitro aerodynamic evaluation shows that about 56% of the powder should deposits in the lungs, with about 27% in the alveolar region, an improvement as compared with the micronized powder available with the Spinhaler. After pulmonary administration to rats contaminated with PuO(2), a 3-fold increase of the Pu urinary excretion was observed, but the dissolution of PuO(2) in the lungs was not enhanced.

  8. Synthesis and Characterization of a Eu-DTPA-PEGO-MSH(4) Derivative for Evaluation of Binding of Multivalent Molecules to Melanocortin Receptors1

    PubMed Central

    Xu, Liping; Vagner, Josef; Alleti, Ramesh; Rao, Venkataramanarao; Jagadish, Bhumasamudram; Morse, David L.; Hruby, Victor J.; Gillies, Robert J.

    2010-01-01

    A labeled variant of MSH(4), a tetrapeptide that binds to the human melanocortin 4 receptor (hMC4R) with low µM affinity, was prepared by solid phase synthesis methods, purified, and characterized. The labeled ligand, Eu-DTPA-PEGO-His-dPhe-Arg-Trp-NH2, exhibited a Kd for hMC4R of 9.1±1.4 µM, approximately 10-fold lower affinity than the parental ligand. The labeled MSH(4) derivative was employed in a competitive binding assay to characterize the interactions of hMC4R with monovalent and divalent MSH(4) constructs derived from squalene. The results were compared with results from a similar assay that employed a more potent labeled ligand, Eu-DTPA-NDP-α-MSH. While results from the latter assay reflected only statistical effects, results from the former assay reflected a mixture of statistical, proximity, and/or cooperative binding effects. PMID:20304640

  9. The safety and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) booster vaccine in healthy Vietnamese children.

    PubMed

    Anh, Dang Duc; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay

    2016-08-17

    Despite effective infant immunization against pertussis, the disease continues to circulate due to waning immunity. Booster vaccinations against pertussis beyond infancy are widely recommended. In Vietnam, however, no recommendations for pertussis boosters beyond the second year of life exist. This open-label, single-centre study was designed to assess the safety of a single booster dose of reduced-antigen-content-diphtheria-tetanus-acellular-pertussis vaccine (dTpa) in 300 healthy Vietnamese children (mean age 7.9years), who had completed primary vaccination against diphtheria, tetanus and pertussis. Solicited symptoms were recorded for 4days and unsolicited and serious adverse events (SAEs) for 31days post-vaccination. Pain and fatigue were the most common solicited local and general symptoms in 35.0% and 14.0% of children, respectively. Grade 3 swelling occurred in 3 children; no large injection site reactions or SAEs were reported. The dTpa booster vaccine was well tolerated and this study supports its administration in school age Vietnamese children.

  10. Unusual Use of Gd-EOB-DTPA in MRCP in Order to Reveal the Source of Bile Leakage in a Patient with Neuroendocrine Tumor – Case Report

    PubMed Central

    Mazur, Rafał; Pawluś, Aleksander; Szymańska, Kinga; Patyk, Mateusz; Otlewska, Anna; Międzybrodzki, Krzysztof; Sokołowska-Dąbek, Dąbrówka; Kubicka, Eliza; Zaleska-Dorobisz, Urszula

    2016-01-01

    Summary Background MRCP is the method of choice in diagnosing pathologies of the biliary system. One of them is bile fistulae. They are uncommon but tend to cause many diagnostic problems. The possible way to improve MRCP is using it with intravenous injection of hepatobiliary-specific contrast agents. As it is eliminated via the hepatobiliary system, it can be visualized in the bile ducts and may help to reveal disorders undetected by a standard MRCP. Case Report We report a case of a 36-year-old woman with leakage in the biliary system which led to creation of a subcutaneous bile reservoir. By means of a regular MRCP protocol it was impossible to reveal any disorders of the biliary system and thus a decision to inject Gd-EOB-DTPA was taken. As a result, a fistula with its opening in the fundus of the gall bladder was revealed. Patient was qualified for treatment with somatostatin analogues in order to stop bile secretion. Conclusions The Gd-EOB-DTPA in combination with regular T2-weighted MRCP may be helpful in detecting anomalies of the biliary system. Although a high price of the procedure restricts its accessibility, such advantages as lower risk of complications, lower costs of hospitalization, and less traumatic nature make it a technique that may take precedence over ERCP in ambiguous cases. PMID:27920840

  11. Discrepancies between the fate of myoblast xenograft in mouse leg muscle and NMR label persistency after loading with Gd-DTPA or SPIOs.

    PubMed

    Baligand, C; Vauchez, K; Fiszman, M; Vilquin, J-T; Carlier, P G

    2009-06-01

    1H-NMR (nuclear magnetic resonance) imaging is regularly proposed to non-invasively monitor cell therapy protocols. Prior to transplantation, cells must be loaded with an NMR contrast agent (CA). Most studies performed so far make use of superparamagnetic iron oxide particles (SPIOs), mainly for favorable detection sensitivity. However, in the case of labeled cell death, SPIO recapture by inflammatory cells might introduce severe bias. We investigated whether NMR signal changes induced by preloading with SPIOs or the low molecular weight gadolinium (Gd)-DTPA accurately monitored the outcome of transplanted cells in a murine model of acute immunologic rejection. CA-loaded human myoblasts were grafted in the tibialis anterior of C57BL/6 mice. NMR imaging was repeated regularly until 3 months post-transplantation. Label outcome was evaluated by the size of the labeled area and its relative contrast to surrounding tissue. In parallel, immunohistochemistry assessed the presence of human cells. Data analysis revealed that CA-induced signal changes did not strictly reflect the graft status. Gd-DTPA label disappeared rapidly yet with a 2-week delay compared with immunohistochemical evaluation. More problematically, SPIO label was still visible after 3 months, grossly overestimating cell survival (<1 week). SPIOs should be used with extreme caution to evaluate the presence of grafted cells in vivo and could hardly be recommended for the long-term monitoring of cell transplantation protocols.

  12. Effect of MPL 9000 extracorporeal shock wave lithotripsy on renal hemodynamics and urine flow: assessment by 99mTc-DTPA renal scintigraphy.

    PubMed

    Naito, S; Yoshida, T; Ogata, N; Ichiya, Y; Koga, H; Kotoh, S; Masuda, K; Kumazawa, J

    1995-01-01

    The effect of extracorporeal shock wave lithotripsy (ESWL) with an MPL9000 lithotriptor on renal hemodynamics and urine flow was investigated by 99mTc-DTPA renal scintigraphy. In the first-pass scintigrams obtained within 1 min after injection of 99mTc-DTPA, there was no significant change in the time to the maximum radioactivity level and the maximum radioactivity ratio at 1 day before ESWL and 1 day or 1 month after ESWL. However, analysis of 30-min scintigrams showed that urinary clearance of radioactivity was delayed in the treated kidney 1 day after ESWL, particularly in the region targeted by shock waves, despite the absence of overt urinary tract obstruction by residual stone fragments. This change was reversible and was no longer noted 1 month after ESWL. These results suggest that ESWL with the MPL9000 lithotriptor induces a focal and temporary decrease in urine flow in the treated kidney, but has little or no effect on renal hemodynamics.

  13. A competitive indirect enzyme-linked immunoassay for lead ion measurement using mAbs against the lead-DTPA complex.

    PubMed

    Xiang, Jun-jian; Zhai, Yi-fan; Tang, Yong; Wang, Hong; Liu, Bin; Guo, Chang-wei

    2010-05-01

    Immunoassays for quantitative measurement of environmental heavy metals offer several advantages over other traditional methods. To develop an immunoassay for lead, Balb/c mice were immunized with a lead-chelate-protein conjugate to allow maximum exposure of the metal to the immune system. Three stable hybridoma cell lines were obtained through spleen cells fusion with Sp2/0 cells. One cell line, 2A11D11, produced mAbs with preferential selectivity and sensitivity for Pb-DTPA than DTPA, exhibiting an affinity constant of 3.34 + or - 0.24 x 10(9) M(-1). Cross reactivity (CR) with other metals were below 1%, except for Fe(III) with a CR less than 5%. This quantitative indirect ELISA for the lead ion was used to detect environmental lead content in local water sources; importantly, the results from the immunoassay were in excellent agreement with those from ICP-MS. Development of immunoassays for metal ions may thus facilitate the detection and regulation of environmental pollution.

  14. Biokinetics and dosimetry of 111In-DOTA-NOC-ATE compared with 111In-DTPA-octreotide.

    PubMed

    Boubaker, Ariane; Prior, John O; Willi, Jean-Pierre; Champendal, Melanie; Kosinski, Marek; Bischof Delaloye, Angelika; Maecke, Helmut R; Ginj, Mihaela; Baechler, Sébastien; Buchegger, Franz

    2012-12-01

    The biokinetics and dosimetry of (111)In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and (111)In-DTPA-octreotide (Octreoscan™, OCTREO) were compared in the same patients. Seventeen patients (10 men, 7 women; mean age 60 years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior-posterior scans were recorded 0.5 (100 % reference scan), 4, 24 and 48 h (17 patients) and 120 h (5 patients) after injection. In 16 patients the OCTREO scan (178 ± 15 MBq) was performed 16 ± 5 days before the NOCATE scan (108 ± 14 MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5 min to 48 h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM. Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p < 0.001) and remained so over time. Whole-body activity showed similar α and β half-lives, but the β fraction of NOCATE was double that of OCTREO. Blood T (1/2)β for NOCATE was longer (19 vs. 6 h). As a result, the effective dose of NOCATE (105 μSv/MBq) exceeded that of OCTREO (52 μSv/MBq), and the latter result was similar to the ICRP 106 value of 54 μSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5 % of NOCATE and OCTREO attached to globular blood components. NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTREO.

  15. Specific lipase-responsive polymer-coated gadolinium nanoparticles for MR imaging of early acute pancreatitis.

    PubMed

    Zhang, Hong-Wu; Wang, Li-Qin; Xiang, Qing-Feng; Zhong, Qian; Chen, Lu-Ming; Xu, Cai-Xia; Xiang, Xian-Hong; Xu, Bo; Meng, Fei; Wan, Yi-Qian; Deng, David Y B

    2014-01-01

    Currently, available methods for diagnosis of acute pancreatitis (AP) are mainly dependent on serum enzyme analysis and imaging techniques that are too low in sensitivity and specificity to accurately and promptly diagnose AP. The lack of early diagnostic tools highlights the need to search for a highly effective and specific diagnostic method. In this study, we synthesized a conditionally activated, gadolinium-containing, nanoparticle-based MRI nanoprobe as a diagnostic tool for the early identification of AP. Gadolinium diethylenetriaminepentaacetic fatty acid (Gd-DTPA-FA) nanoparticles were synthesized by conjugation of DTPA-FA ligand and gadolinium acetate. Gd-DTPA-FA exhibited low cytotoxicity and excellent biocompatibility when characterized in vitro and in vivo studies. L-arginine induced a gradual increase in the intensity of the T1-weighted MRI signal from 1 h to 36 h in AP rat models. The increase in signal intensity was most significant at 1 h, 6 h and 12 h. These results suggest that the Gd-DTPA-FA as an MRI contrast agent is highly efficient and specific to detect early AP.

  16. Development and Characterization of the Recombinant Human VEGF-EGF Dual-Targeting Fusion Protein as a Drug Delivery System.

    PubMed

    Li, Jia-Je; Lan, Keng-Li; Chang, Shun-Fu; Chen, Ya-Fen; Tsai, Wen-Chun; Chiang, Pei-Hsun; Lin, Meng-Han; Fischer, Wolfgang B; Shih, Yi-Sheng; Yen, Sang-Hue; Liu, Ren-Shyan; Tsay, Yeou-Guang; Wang, Hsin-Ell; Chang, Cheng Allen

    2015-12-16

    The design, preparation, as well as structural and functional characterizations of the recombinant fusion protein hVEGF-EGF as a dual-functional agent that may target both EGFR (R: receptor) and angiogenesis are reported. hVEGF-EGF was found to bind to EGFR more strongly than did EGF, and to bind to VEGFR similarly to VEGF. Mass spectrometry measurements showed that the sites of DTPA (diethylenetriaminepentaacetic acid) conjugated hVEGF-EGF (for radiolabeling) were the same as those of its parent hEGF and hVEGF proteins. All DTPA-conjugated proteins retained similar binding capacities to their respective receptors as compared to their respective parent proteins. In vitro cell binding studies using BAEC (a bovine aortic endothelial cell) and MDA-MB-231 (a human breast cancer) cells expressing both EGFR and VEGFR confirmed similar results. Treating BAEC cells with hVEGF-EGF induced remarkable phosphorylation of EGFR, VEGFR, and their downstream targets ERK1/2. Nevertheless, the radiolabeled (111)In-DTPA-hVEGF-EGF showed cytotoxicity against MDA-MB-231 cells. Pharmacokinetic studies using (111)In-DTPA-hVEGF-EGF in BALB/c nude mice showed that appreciable tracer activities were accumulated in liver and spleen. In all, this study demonstrated that the fusion protein hVEGF-EGF maintained the biological specificity toward both EGFR and VEGFR and may be a potential candidate as a dual-targeting moiety in developing anticancer drugs.

  17. Graphene oxide based theranostic platform for T1-weighted magnetic resonance imaging and drug delivery.

    PubMed

    Zhang, Mengxin; Cao, Yuhua; Chong, Yu; Ma, Yufei; Zhang, Hailu; Deng, Zongwu; Hu, Chunhong; Zhang, Zhijun

    2013-12-26

    Magnetic resonance imaging (MRI) is a powerful and widely used clinical technique in cancer diagnosis. MRI contrast agents (CAs) are often used to improve the quality of MRI-based diagnosis. In this work, we developed a positive T1 MRI CA based on graphene oxide (GO)-gadolinium (Gd) complexes. In our strategy, diethylenetriaminepentaacetic acid (DTPA) is chemically conjugated to GO, followed by Gd(III) complexation, to form a T1 MRI CA (GO-DTPA-Gd). We have demonstrated that the GO-DTPA-Gd system significantly improves MRI T1 relaxivity and leads to a better cellular MRI contrast effect than Magnevist, a commercially used CA. Next, an anticancer drug, doxorubicin (DOX), was loaded on the surface of GO sheets via physisorption. Thus-prepared GO-DTPA-Gd/DOX shows significant cytotoxicity to the cancer cells (HepG2). This work provides a novel strategy to build a GO-based theranostic nanoplatform with T1-weighted MRI, fluorescence imaging, and drug delivery functionalities.

  18. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging.

    PubMed

    Vergara, Irene; Castillo, Erick Y; Romero-Piña, Mario E; Torres-Viquez, Itzel; Paniagua, Dayanira; Boyer, Leslie V; Alagón, Alejandro; Medina, Luis Alberto

    2016-03-26

    The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx). The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with