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Correlation of chromosome patterns in human leukemic cells with exposure to chemicals and/or radiation. Comprehensive progress report, July 1991--June 1992

Description: This project seeks to defining the chromosome segments associated with radiation induced leukemogenesis (treatment-related acute myeloid leukemia, or t-AML). Towards these goals genetic analysis of human chromosomes 5 and 7 continues to investigate correlation of treatment with balanced and unbalanced chromosomal translocations. Progress is being made in cloning the breakpoints in balanced translocations in t-AML, that is to clone the t(9;11) and t(11;19) breakpoints, to clone the t(3;21)(q26;q22) breakpoints and to determine the relationship of these translocations to prior exposure to topoisomerase II inhibitors. 11 figs. 3 figs.
Date: June 1, 1992
Creator: Rowley, J. D.
Partner: UNT Libraries Government Documents Department

Use of supercritical carbon dioxide fluid as a solvent for the purification of pet radiotracers

Description: We have identified superfluid chromatography (SFC) as a promising method which could offer advantages in radiotracer purification through rapid separation, as well as, improved recovery and purity of labeled product. Using SF CO{sub 2} as the mobile phase for chromatographic separation of labeled product would eliminate the need for solvent removal from product prior to delivery.
Date: December 31, 1993
Creator: Ferrieri, R. A.; Fowler, J. S. & Wolf, A. P.
Partner: UNT Libraries Government Documents Department

SPECT assay of radiolabeled monoclonal antibodies. Comprehensive progress report, September 1989--February 1992

Description: The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ({sup 123}I, {sup 131}I, and {sup 111}In) and with another radionuclide,{sup 211}At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for {sup 111}In and {sup 123}I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches.
Date: February 1, 1992
Creator: Jaszczak, R. J.
Partner: UNT Libraries Government Documents Department

[Non-invasive evaluation of the cardiac autonomic nervous system by PET]. Progress report, September 1991--September 1992

Description: The proposed research addresses the development, validation and application of cardiac PET imaging techniques to characterize the autonomic nervous system of the heart. PET technology has significantly matured over the last two decades. Instrument design, image processing and production of radiochemical compounds have formed an integrative approach to provide a powerful and novel imaging modality for the quantitative in vivo evaluation of the autonomic nervous system of the heart. Animal studies using novel tracers for the sympathetic and parasympathetic nerve terminals will be employed to characterize the functional integrity of nerve terminals. This work will be complemented by the development of agents which bind to postsynaptic receptor sites. The combined evaluation of presynaptic and postsynaptic neuronal function will allow a unique characterization of neuronal function. Initial development in animal studies will be followed by feasibility studies in humans. These studies are designed to test sophisticated imaging protocols in the human heart and validate the scintigraphic findings with independent markers of autonomic innervation. Subsequent clinical application in various cardiac diseases is expected to provide new insights into the neuropathophysiology of the heart.
Date: September 1, 1992
Partner: UNT Libraries Government Documents Department

Nuclear medicine and imaging research (quantitative studies in radiopharmaceutical science). Progress report, January 1, 1992--December 31, 1992

Description: This report describes three studies aimed at using radiolabeled pharmaceuticals to explore brain function and anatomy. The first section describes the chemical preparation of [F18]fluorinated benzamides (dopamine D-2 receptor tracers), [F18]fluorinated benzazepines (dopamine D-1 receptor tracers), and tissue distribution of [F18]-fluoxetine (serotonin reuptake site tracer). The second section relates pharmacological and behavioral studies of amphetamines. The third section reports on progress made with processing of brain images from CT, MRI and PET/SPECT with regards to brain metabolism of glucose during mental tasks.
Date: June 1, 1992
Creator: Cooper, M. & Beck, R. N.
Partner: UNT Libraries Government Documents Department

In vivo metabolism of I-123 labeled semisynthetic low density lipoproteins. Final technical report, September 28, 1988--September 27, 1990

Description: We previously observed that small model beta-strand peptides (MBPs) selectively bind to human low density lipoprotein (hLDL) in vitro, and that some MBPs can be labeled with I-123-tyramine cellobiose (I-123-TyC). We hypothesized that metabolism of semisynthetic hLDL should mimic that of covalently labeled native hLDL, and planned to evaluate the biodistribution in rabbits of semisynthetic hLDL; to determine effects of prior oxidation and acetylation of the adsorbing hLDL on binding of MBPs and upon biodistribution of semisynthetic particles; and to begin biodistribution studies with semisynthetic hLDL in human subjects, with the eventual goal of application to experimental and clinical nuclear imaging studies. We have synthesized a radioiodotyrosine-containing MBP, designated betay, as a more suitable adsorbant to hLDL thanradioiodine-TyC-MBP, and optimized conditions for preparing radioiodine-betaY:hLDL. In rabbits both betaY and betaY:hLDL complexes were cleared from the bloodstream much more rapidly than radioiodine-TyC-hLDL or In-111-hLDL, and betaY in either form showed a biodistribution pattern different from that of directly radiolabeled hLDL. Even though radioiodine-betaY can be quickly and easily produced, we conclude that neither betaY alone nor semisynthetic betaY:hLDL particles are likely to prove useful as tracers of hLDL metabolism in vivo.
Date: December 1, 1990
Creator: Harper, P. V.
Partner: UNT Libraries Government Documents Department

Scintillation materials for medical applications. Annual progress report, January 1, 1991--December 31, 1992

Description: Scintillators are beginning to attract renewed attention because modern High Energy Physics accelerators are placing unprecedented demands of quantity and quality of detector materials and Positron Emission Tomography (PET), used by the medical field. Both applications required materials for scintillator detectors with properties beyond those delivered by traditional scintillators. Thallium doped halides are very efficient, but slow and chemically unstable. Two modern developments, namely the very fast BaF{sub 2}, which owed its success to the newly discovered crossover transitions, and CeF{sub 3}, which carried a promise of fast components, more practical wavelengths and attractive efficiency. Since traditional scintillators (Tl doped halides) are very efficient, and could be even more efficient at larger concentrations of Tl, if it were not for concentration quenching. However Tl transitions are spin forbidden and slow. Both ills could be remedied by replacing Tl with Ce, whose transitions are allowed and which is known to form fully concentrated compounds of high photoluminescent efficiency and no quenching. These materials, plus new Ce-doped materials, exhibiting highly promising properties for medical applications, became the target of our studies.
Date: December 31, 1992
Creator: Lempicki, A. & Wojtowicz, A. J.
Partner: UNT Libraries Government Documents Department

Improving cancer treatment with cyclotron produced radionuclides. Comprehensive progress report, February 1, 1990--January 31, 1993

Description: This report describes the author`s continuing long term goal of promoting nuclear medicine applications by improving the scientific basis for tumor diagnosis treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The program has 3 interactive components: Radiochemistry /Cyclotron; Pharmacology; and Immunology. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Cyclotron section under the DOE grant during the 1989--1992 grant period, will be employed in the Pharmacology and Immunology sections of the DOE grant during the 1992--1995 grant period. The development of novel radionuclides and tracers is of course useful in and of itself, but their utility is greatly enhanced by the interaction with the immunology and pharmacology components of the program.
Date: August 4, 1992
Creator: Larson, S. M. Finn, R. D.
Partner: UNT Libraries Government Documents Department

SPECT assay of radiolabeled monoclonal antibodies. Third yearly progress report, September 1991--February 1992

Description: The accurate determination of the biodistribution of radiolabeled monoclonal antibodies (MoAbs) is important for calculation of dosimetry and evaluation of pharmacokinetic variables such as antibody dose and route of administration. The hypothesis of this application is that the biodistribution of radiolabeled monoclonal antibodies (MoAbs) can be quantitatively determined using single photon emission computed tomography (SPECT). The major thrusts during the third year include the continued development and evaluation of improved 3D SPECT acquisition and reconstruction approaches to improve quantitative imaging of radiolabeled monoclonal antibodies (MoAbs), and the implementation and evaluation of algorithms to register serial SPECT image data sets, or to register 3D SPECT images with 3D image data sets acquired from positron emission tomography (PEI) and magnetic resonance images (MRI). The research has involved the investigation of statistical models and iterative reconstruction algorithms that accurately account for the physical characteristics of the SPECT acquisition system. It is our belief that SPECT quantification can be improved by accurately modeling the physical processes such as attenuation, scatter, geometric collimator response, and other factors that affect the measured projection data.
Date: February 1, 1992
Creator: Jaszczak, R. J.
Partner: UNT Libraries Government Documents Department

High resolution tomographic instrument development

Description: Our recent work has concentrated on the development of high-resolution PET instrumentation reflecting in part the growing importance of PET in nuclear medicine imaging. We have developed a number of positron imaging instruments and have the distinction that every instrument has been placed in operation and has had an extensive history of application for basic research and clinical study. The present program is a logical continuation of these earlier successes. PCR-I, a single ring positron tomograph was the first demonstration of analog coding using BGO. It employed 4 mm detectors and is currently being used for a wide range of biological studies. These are of immense importance in guiding the direction for future instruments. In particular, PCR-II, a volume sensitive positron tomograph with 3 mm spatial resolution has benefited greatly from the studies using PCR-I. PCR-II is currently in the final stages of assembly and testing and will shortly be placed in operation for imaging phantoms, animals and ultimately humans. Perhaps the most important finding resulting from our previous study is that resolution and sensitivity must be carefully balanced to achieve a practical high resolution system. PCR-II has been designed to have the detection characteristics required to achieve 3 mm resolution in human brain under practical imaging situations. The development of algorithms by the group headed by Dr. Chesler is based on a long history of prior study including his joint work with Drs. Pelc and Reiderer and Stearns. This body of expertise will be applied to the processing of data from PCR-II when it becomes operational.
Date: August 1, 1992
Partner: UNT Libraries Government Documents Department

[A clinical trial of neutron capture therapy for brain tumors]. Technical progress report, 1990

Description: This document briefly describes recent advances in the author`s laboratory. Topics described include neutron beam design, high- resolution autoradiography, boronated phenylalanine (BPA) distribution and survival studies in glioma bearing mice, computer- aided treatment planning, prompt gamma boron 10 analysis facility at MITI-II, non-rodent BPA toxicity studies, and preparations for clinical studies.
Date: December 31, 1990
Creator: Zamenhof, R. G.
Partner: UNT Libraries Government Documents Department

Preparation of radiopharmaceuticals labeled with metal radionuclides. Progress report, July 1, 1988--June 30, 1992

Description: We recently developed a useful zinc-62/copper-62 generator and are presently evaluating copper-62 radiopharmaceuticals for clinical studies. While developing these copper-62 radiopharmaceuticals, in collaboration with the University of Missouri Research Reactor, Columbia we have also explored copper-64 radiopharmaceuticals. The PET images we obtained with copper-64 tracers were of such high quality that we have developed and evaluated copper-64 labeled antibodies for PET imaging. The major research activities described herein include: the development and assessment of gallium-68 radiopharmaceuticals; the development and evaluation of a new zinc-62/copper-62 generator and the assessment of copper-62 radiopharmaceuticals; mechanistic studies on proteins labeled with metal radionuclides.
Date: June 1, 1992
Creator: Welch, M. J.
Partner: UNT Libraries Government Documents Department

Chemoprevention by WR-2721

Description: WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL {times} BALB/c F{sub 1} female mice, were exposed to a single whole-body dose of 206 cGy from a {sup 60}Co photon source. Those groups treated with VATR-2721 (400 mg/kg) were administered the agent i.p. 30 min prior to irradiation. Over 90% of deaths were determined to be due to tumor involvement. WR-2721 afforded significant protection against life shortening due to radiation-induced tumors of connective tissue and epithelial tissue origins. Subsequent survival time in WR-2721-treated and irradiated animals as compared to matched irradiated-only controls was extended up to 59 days. A single exposure of animals to VVR-2721 did not affect the cumulative survival curves for unirradiated mice. WR-2721 possesses chemopreventive properties which can be clinically exploited to reduce the risk to therapy-induced secondary cancers in patients who otherwise would have an excellent prognosis for cure and long-term survival.
Date: May 1, 1993
Creator: Grdina, D. J. & Carnes, B. A.
Partner: UNT Libraries Government Documents Department

Laboratory and cyclotron requirements for PET research

Description: This report describes four types of PET facilities: Clinical PET with no radionuclide production; clinical PET with a small accelerator; clinical PET with research support; and research PET facilities. General facility considerations are also discussed.
Date: June 1, 1993
Creator: Schlyer, D. J.
Partner: UNT Libraries Government Documents Department

The development of iodine-123-methyl-branched fatty acids and their applications in nuclear cardiology

Description: Continued Interest in the use of iodine-1 23-labeled fatty acids for myocardial Imaging results from observations from a variety of studies that in many types of cardiac disease, regional fatty acid myocardial uptake patterns are often different than regional distribution of flow tracers. These differences may reflect alterations in important parameters of metabolism which can be useful for patient management or therapeutic strategy decision making. In addition, use of iodine-I 23-labeled fatty acid distribution may represent a unique metabolic probe to relate some aspects of the metabolism of these substrates with the regional viability of cardiac tissue. The use of such viability markers could provide important prognostic information on myocardial salvage, helping to identify patients for revascularization or angioplasty. Clinical studies are currently in progress with the iodine-123-labeled 1 5-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue at several institutions. The goals of this paper are to discuss development of the concept of metabolic trapping of fatty acids, to briefly review development and evaluation of various radioiodinated methyl-branched fatty acids and to discuss recent patient studies with iodine-123 (BMIPP) using single photon emission computerized tomography (SPECT).
Date: June 1, 1993
Creator: Knapp, F. F. Jr.; Ambrose, K. R.; Kropp, J.; Biersack, H. J.; Goodman, M. M.; Franken, P. et al.
Partner: UNT Libraries Government Documents Department

INEL BNCT Research Program, March/April 1993

Description: This report presents summaries for two months of current research of the Idaho National Engineering Laboratory Boron Neutron Capture Therapy Program. Information is presented on development and murine screening experiments of low-density lipoprotein, carboranyl alanine, and liposome boron containing compounds. Pituitary tumor cell culture studies are described. Drug stability, pharmacology and toxicity evaluation of borocaptate sodium and boronophenylalanine are described. Treatment protocol development via the large animal (canine) modal studies and physiological response evaluation in rats are discussed. Supporting technology development and technical support activities for boron drug biochemistry and purity, analytical and measurement dosimetry, and noninvasive boron quantification activities are included for the current time period. Current publications for the two months are listed.
Date: June 1, 1993
Creator: Venhuizen, J. R.
Partner: UNT Libraries Government Documents Department

INEL BNCT Research Program annual report, 1992

Description: This report is a summary of the progress and research produced for the Idaho National Engineering Laboratory Boron Neutron Capture Therapy (BNCT) Research Program for calendar year 1992. Contributions from all the principal investigators about their individual projects are included, specifically, chemistry (pituitary tumor targeting compounds, boron drug development including liposomes, lipoproteins, and carboranylalanine derivatives), pharmacology (murine screenings, toxicity testing, inductively coupled plasma-atomic emission spectroscopy (ICP-AES) analysis of biological samples), physics (radiation dosimetry software, neutron beam and filter design, neutron beam measurement dosimetry), and radiation biology (small and large animal models tissue studies and efficacy studies). Information on the potential toxicity of borocaptate sodium and boronophenylalanine is presented, results of 21 spontaneous-tumor-bearing dogs that have been treated with BNCT at the Brookhaven National Laboratory (BNL) Medical Research Reactor (BMRR) are discussed, and predictions for an epithermal-neutron beam at the Georgia Tech Research Reactor (GTRR) are shown. Cellular-level boron detection and localization by secondary ion mass spectrometry, sputter-initiated resonance ionization spectroscopy, low atomization resonance ionization spectroscopy, and alpha track are presented. Boron detection by ICP-AES is discussed in detail. Several boron carrying drugs exhibiting good tumor uptake are described. Significant progress in the potential of treating pituitary tumors with BNCT is presented. Measurement of the epithermal-neutron flux at BNL and comparison to predictions are shown. Calculations comparing the GTRR and BMRR epithermal-neutron beams are also presented. Individual progress reports described herein are separately abstracted and indexed for the database.
Date: May 1, 1993
Creator: Venhuizen, J. R.
Partner: UNT Libraries Government Documents Department

No-carrier-added (NCA) aryl [{sup 18}F]fluorides via the nucleophilic aromatic substitution of electron rich aromatic rings

Description: A method for synthesizing no-carrier-added (NCA) aryl [{sup 18}F] fluoride substituted aromatic aldehyde compositions bearing an electron donating group is described. The method includes the step of reacting aromatic nitro aldehydes having a suitably protected hydroxyl substituent on an electron rich ring. The reaction is carried out by nucleophilic aromatic substitution with a no-carrier-added (NCA) [{sup 18}F]fluoride ion. The method can be used to synthesize various no-carrier-added aryl [{sup 18}F]fluoride compositions, including 6-[{sup 18}F]fluoro-L-DOPA, 2-[{sup 18}F]fluorotyrosine, 6-[{sup 18}F]fluoronorepinephrine, and 6-[{sup 18}F]fluorodopamine. In those instances when a racemic mixture of enantiomers is produced by the present invention, such as in the synthesis of 6-[{sup 18}F]fluoronorepinephrine, a preferred method also includes resolution of the racemic mixture on a chiral HPLC column. This procedure results in a high yield of enantiomerically pure [{sup 18}F] labeled isomers, for example [-]-6-[{sup 18}F]fluoronorepinephrine and [+]-6-[{sup 18}F]fluoronorepinephrine.
Date: December 31, 1991
Creator: Ding, Yu-Shin; Fowler, J. S. & Wolf, A. P.
Partner: UNT Libraries Government Documents Department

Development of radiohalogenated muscarinic ligands for the in vivo imaging of m-AChR by nuclear medicine techniques

Description: Alterations in the density of acetylcholinergic muscarinic receptors (m-AChR) have been observed in various dementias. This has spurred interest in the development of radiohalogenated ligands which can be used for the non-invasive in vivo detection of m-AChR by nuclear medicine techniques. We have developed a new ligand 1-azabicyclo[2.2.2]oct-3-yl ({alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IQNP,12) which demonstrates high affinity for the muscarinic receptor. When labeled with radioiodine it has been shown to be selective and specific for m-ACHR. Initial studies on the separation and in vivo evaluation of the various isomers of IQNP have shown that the stereochemistry of the chiral centers and the configuration around the double bond play an important role in m-AChR subtype specificity. In vivo evaluation of these stereoisomers demonstrate that E-(R,R)-IQNP has a high affinity for the M{sub 1} muscarinic subtype while Z-(R,R)-IQNP demonstrate a high affinity for M{sub 1} and M{sub 2} receptor subtypes. These data demonstrate IQNP (12) has potential for use in the non-evasive in vivo detection of m-AChR by single photon emission computed tomography (SPECT). A brominated analogue, ``BrQNP,`` in which the iodine has been replaced by a bromine atom, has also been prepared and was shown to block the in vivo uptake of IQNP in the brain and heart and therefore has potential for positron emission tomographic (PET) studies of m-AChR.
Date: June 1, 1994
Creator: McPherson, D. W.; Luo, H. & Knapp, F. F. Jr.
Partner: UNT Libraries Government Documents Department

Nuclear Medicine Program progress report for quarter ending March 31, 1993

Description: We have exploring the possibility of measuring urinary radioactivity as an index of pancreatic lipase activity after oral administration of a new triglyceride containing a radioactive iodine-1 25-labeled fatty acid moiety. The new agent, 1,2-dipalmitoyl-3[15-(p-iodophenyl)pentandecan-l-oyl]-racglycerol (1,2-Pal-3-IPPA), was prepared by the thallation-iodide displacement method. Following oral gavage of the radioiodinated triglyceride to rats, about 30% of the administered activity was excreted in 24 hours in the urine. In normal human controls an higher urinary excretion (of about 75% was observed. In this report, we describe an evaluation of the metabolites excreted in the urine and the chemical species stored in adipose from rats. The urine activity co-chromatographed with hippuric acid by TLC indicating conjugation of the IPPA metabolites. Release of the acidic components from the conjugated excretory products by acid hydrolysis of the urine provided the radioactive acidic IPPA metabolites. Analysis of the Folch extracts of fat samples from rats demonstrated that the radioactive components co-chromatographed In the triglyceride region. Recent studies in patients with compromised pancreatic exocrine function have demonstrated significantly decreased 24 hr. urinary excretion of about 25%, following oral administration of [1 -1 31]-1,2-Pal-3-IPPA. Thus, urine analysis after oral administration of [I -1 31]-1,2-Pal-3-IPPA may be a simple, non-invasive tool for the clinical evaluation of various diseases involving dietary fat digestion.
Date: April 1, 1993
Creator: Knapp, F. F. Jr.; Ambrose, K. R.; Beets, A. L.; Callahan, A. P.; McPherson, D. W.; Mirzadeh, S. et al.
Partner: UNT Libraries Government Documents Department