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Radioimmunotherapy: Development of an effective approach. Progress report, 1987

Description: Goals of this program are to answer the fundamental scientific questions for the development of an effective approach for delivering radiation therapy to cancer on antibody-based radiopharmaceuticals. The following list consists of highlights of developments from our program: documented therapeutic response of lymphoma in patients receiving radioimmunotherapy; development and application of quantitative radionuclide imaging techniques for therapy planning and dosimetry calculations; multicompartmental modeling and analysis of the in vivo MoAb kinetics in patients; a MoAb macrocycle chelate for Cu-67: development, production, in vitro and in vivo testing; NMR analysis of immunoradiotherapeutic effects on the metabolism of lymphoma; analysis of the variable molecular characteristics of the MoAb radiopharmaceutical, and their significance; in vivo studies in mice and patients of the metabolism of radioiodinated MoAb as well as In-111 CITC MoAb; and biodistribution of Cu-67 TETA MoAb in nude mice with human lymphoma.
Date: December 31, 1987
Partner: UNT Libraries Government Documents Department

The coordination chemistry of technetium and rhenium and applications to nuclear medicines. [Annual] technical report, April 1, 1993--December 31, 1993

Description: The dramatic dependence of Re-binding to functionalized hydrazines on the nature of the coligands associated with the metal site has led to an examination of alkoxy and thiolato ligand types. The observation that multidentate thiolate ligands are highly effective in this latter role suggests the design and synthesis of new chelating polythiolate ligands with high binding affinities for radiometallic nuclides and of functionalized polythiolate ligands for the preparation of radionuclide-conjugated antibodies or peptides and the preparation and characterization of their complexes not only with the Group 7 metals Tc and Re but with the Group 13 metals Ga and In, which also possess radionuclides with useful properties. Since the rational design of these novel bifunctional conjugates requires a fundamental understanding of the coordination chemistry of relevant metals with polythiolate ligands whose syntheses and properties remain unexplored, effort has been directed toward the preparation of novel polythiolate ligands and the characterization of their complexes with Group 7 and Group 13 metals. This report describes studies on several complementary aspects of the coordination chemistry of the pyridinethiolate derived ligands 2-HSC{sub 5}NH{sub 3}-SiR{sub 3}, 2-HSC{sub 5}NH{sub 3}-6-SiR{sub 3} and 2-HSC{sub 5}NH{sub 2}-3,6-SiR{sub 3} and the potentially bifunctional polythiolate ligand HOOCCH{sub 2}Si(CH{sub 2}CH{sub 2}SH){sub 3} have been synthesized; of several aspects of rhenium-hydrazido and rhenium-thiolate chemistry have been developed; of Ga and In complexes of the 2-pyridinethiolate class of ligands have been synthesized and structurally characterized; and of the general coordination properties of the 2-pyrithinethiolate and related ligand types.
Date: December 31, 1993
Creator: Zubieta, J.
Partner: UNT Libraries Government Documents Department

Preparation of high specific activity technetium-96

Description: The present invention relates to a method of producing Tc-96 from the proton irradiation of a rhodium target and a technique for isolating under remote hot cell conditions the Tc-96 from the proton irradiated target.
Date: December 31, 1990
Creator: Mausner, L. F.; Srivastava, S. C. & Prach, T.
Partner: UNT Libraries Government Documents Department

[Radiopharmacokinetics: Utilization of nuclear medicine]. Comprehensive progress report, [1986--1989]

Description: The work performed in the 1986/1989 period can be characterized as one of testing and documenting that the Radiopharmacokinetic technique is both feasible and applicable to human studies, as well as developing spectroscopic methods for undertaking noninvasive human studies. Main accomplishments include studies which: show that drug targeting can be monitored noninvasively using radiolabeled drugs. The study that documented this finding involved an analysis of the comparative kinetics of biodistribution of {sup 195m}Pt-cisplatin to brain tumors, when administered intravenously and intra-arterially; show that such differential targeting of Platinum represents a differential quantity of drug and a differential amount of the active component reaching the target site; show that in vivo NMRS studies of drugs are possible, as documented by our studies of 5-fluorouracil; show that 5-fluorouracil can be trapped in tumors, and that such trapping may be directly correlatable to patient response; show that the radiopharmacokinetic technique can also be used effectively for the study of radiopharmaceuticals used for imaging, as documented in our studies with {sup 99m}T{sub c}-DMSA.
Date: December 31, 1989
Creator: Wolf, W.
Partner: UNT Libraries Government Documents Department

Isotope-based medical research in the post genome era: Gene-orchestrated life functions in medicine seen and affected by isotopes. Workshop report

Description: The US Department of Energy (DOE) and the National Institutes of Health (NIH) conducted a workshop on Isotope-Based Medical Research in the Post Genome Era at NIH, Bethesda, Maryland, November 12--14, 1997. The workshop aimed at identifying the role of stable and radioisotopes for advanced diagnosis and therapy of a wide range of illnesses using the new information that comes from the human genome program. In this sense, the agenda addressed the challenge of functional genomics in humans. The workshop addressed: functional genomics in clinical medicine; new diagnostic potentials; new therapy potentials; challenge to tracer- and effector-pharmaceutical chemistry; and project plans for joint ventures.
Date: December 31, 1997
Creator: Feinendegen, L. E.
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

Body growth considerations in age-specific dosimetry. Final report

Description: This report describes the manner in which the age-specific dosimetric calculations of the International Commission on Radiological Protection (ICRP) addressed changes in organ size that occur with age. The approach involves an interpolation of dosimetric information derived for six reference individuals using the inverse of the total body mass as the interpolation variable. An alternative formulation is investigated that employs a functional representation of the organ mass as a function of age in conjunction with an explicit formulation of the dosimetric factors in terms of organ mass. Using an exponential-logistic growth function as suggested by Walker, this report demonstrates, through application to the dosimetry of radioiodines in the thyroid, that the alternative formulation can be formulated and implemented. Although either approach provides a workable basis for age-specific dosimetry, it is clear that the functional representation of organ growth has some attractive features. However, without question, the major difficulty is the quality and quantity of data available to address the age- and gender-specific parameters in the dosimetric formulations.
Date: September 30, 1993
Creator: Eckerman, K. F.
Partner: UNT Libraries Government Documents Department

Entombment: It is Time to Reconsider this Technology

Description: It is time to reconsider entombment of nuclear reactors and other facilities. Decommissioning worker exposure and safety, transportation, cost, potential loss of LLW disposal capacity, and need for strong technical basis are shared drivers for the renewed interest in developing the entombment D&D option. Entombment relies on retarding the release of radionuclides for a very long period, a number of factors must be considered prior to selection and implementation of entombment. A technical basis for addressing and evaluating these factors with associated stakeholder acceptance of the technology is needed before entombment becomes an accepted D&D option.
Date: September 1, 2000
Creator: Birk, Sandra Margaret; Hanson, Robert Gail & Vernon, Donald Keith
Partner: UNT Libraries Government Documents Department

PCGAP: Users Guide and Algorithm Description

Description: PCGAP is a software package, which was written to provide gamma-ray pulse height spectrum analysis on a personal computer platform using the Windows NT operating system. It is a collection of programs, which provide a wide range of operability extending from the single user environment to the general purpose counting room. Included in the package are necessary data structures and libraries used to compute quantitative radionuclide concentrations. PCGAP also contains techniques to decontaminate photopeak interferences; determine activity concentrations for radionuclides independent of their associated spectral photopeak size; and three methods to determine the energy scale of a spectrum. PCGAP performs a non-linear least squares fitting of a Gaussian function to spectral photopeaks. The fitting algorithm can fit up to five concurrent photopeaks using a common spectral background. The package includes a program that will automatically locate spectral photopeaks, fit them to a Gaussian function, identify the radionuclides associated with the found photopeaks, and compute a net activity concentration, and for an 8K spectrum do it in less than 30 seconds on a reasonably configured PC. PCGAP also includes a program which allows the operator to manually (using mouse clicks) identify photopeak locations, fit limits and background positions, initiate a fit to the photopeaks and then display the resulting Gaussian function forms. This interactive display function is particularly useful to resolve or properly fit photopeaks with complex adjacent structure and for photopeaks that are near the limit of detection.
Date: June 1, 2000
Creator: Killian, Elmo Wayne
Partner: UNT Libraries Government Documents Department

Discussion of possible content of an IAEA (International Atomic Energy Agency) handbook/computer file for ''Data for Medical Radioisotope Production''

Description: Several possible approaches will be put forward in order to stimulate discussion and seek consensus on the relative emphasis and format of a proposed IAEA handbook and computer file for ''Data for Medical Radioisotope Production.'' An outline for possible chapters for non-nuclear physicists will be presented describing low, medium, and high energy reactions induced by light projectiles (e.g., n,p,..cap alpha..), by photons, and by heavy ions. Qualitative features would be described, typical experimental examples would be presented to illustrate each type of reaction, and examples would be presented of how well various computer codes would permit the calculation/prediction of the experimental results. We next solicit discussion of the desirability of the above, and of the format and means of compilation of a computer data file for isotope production. This should include format of experimental data, and also, whether a calculated file should be presented for production of particular isotopes from a ''most wanted'' list.
Date: April 1, 1987
Creator: Blann, M.
Partner: UNT Libraries Government Documents Department

The antibody approach of labeling blood cells

Description: Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.
Date: December 31, 1991
Creator: Srivastava, S. C.
Partner: UNT Libraries Government Documents Department

Neutron capture therapy: Years of experimentation---Years of reflection

Description: This report describes early research on neutron capture therapy over a number of years, beginning in 1950, speaking briefly of patient treatments but dwelling mostly on interpretations of our animal experiments. This work carried out over eighteen years, beginning over forty years ago. Yet, it is only fitting to start by relating how neutron capture therapy became part of Brookhaven`s Medical Research Center program.
Date: December 16, 1991
Creator: Farr, L. E.
Partner: UNT Libraries Government Documents Department

Major compound-dependent variations of {sup 10}B(n{alpha}){sup 7} Li RBE for the 9L RAT gliosarcoma in vitro and in vivo

Description: Relative biological effectiveness (RBE) values for the high linear-energy-transfer (LET) radiations produced during born neutron capture therapy (BNCT) were determined using the 9L rat gliosarcorna both in vitro and as an intracerebral tumor. In the absence of {sup 10}B, the combined effect of the recoiling protons from the {sup 14}N(n,p){sup 14}C and the {sup 1}H(n,n{prime})p reactions, compared to an iso-effect endpoint produced by 250 kVp x-rays, yielded RBEs for these high-LET protons of 4.4 in vitro and 3.8 in an in vivo/in vitro assay. RBEs for the {sup 10}B(n,{alpha}){sup 7}Li reaction were calculated from cell survival data following reactor irradiation in the presence or in the absence of the either of the amino acid, p-boronophenylalanine (BPA) or the sulfhydryl dodecaborane dimer (BSSB). With BPA, RBE values ranged from 3.5 to 11.4, while under the same set of conditions with BSSB, RBE values ranged from 1.1 to 4.3. In vitro, higher RBEs for the {sup 10}B(n,{alpha}){sup 7}Li reaction using BPA than with BSSB suggest a difference in distribution of {sup 10}B relative to the nucleus.
Date: December 31, 1991
Creator: Coderre, J. A.; Makar, M. S.; Micca, P. L.; Nawrocky, M. M.; Joel, D. D. & Slatkin, D. N.
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

Cancer radioimmunotherapy: Development of an effective approach. Progress report, 1985

Description: The objective of this program is the development of effective approaches for delivering radiation therapy to patients with cancer using radiopharmaceuticals produced from monoclonal antibodies. One major achievement of this program has been the development of a new, Cu-67 chelator (Teta). This chelator firmly holds copper even in the presence of competitive serum proteins. Copper has proven to be labile with other chelators. Also, a single photon emission tomographic camera was purchased with University and philanthropic funds specifically for this program. This allows full-time developmental work on quantitative imaging approaches and in vivo kinetics of our various radiopharmaceutical antibody products. The pharmakinetics of I-123 antibody and antibody fragments have been obtained in patients utilizing quantitative imaging and have demonstrated significant differences as well as the need for long- term studies with I-131 and Cu-67.
Date: December 31, 1985
Creator: DeNardo, S. 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

Emission computed tomography: a new technique for the quantitative physiologic study of brain and heart in vivo

Description: Emission computed tomography can provide a quantitative in vivo measurement of regional tissue radionuclide tracer concentrations. This facility when combined with physiologic models and radioactively labeled physiologic tracers that behave in a predictable manner allow measurement of a wide variety of physiologic variables. This integrated technique has been referred to as Physiologic Tomography (PT). PT requires labeled compounds which trace physiologic processes in a known and predictable manner, and physiologic models which are appropriately formulated and validated to derive physiologic variables from ECT data. In order to effectively achieve this goal, PT requires an ECT system that is capable of performing truly quantitative or analytical measurements of tissue tracer concentrations and which has been well characterized in terms of spatial resolution, sensitivity and signal to noise ratios in the tomographic image. This paper illustrates the capabilities of emission computed tomography and provides examples of physiologic tomography for the regional measurement of cerebral and myocardial metabolic rate for glucose, regional measurement of cerebral blood volume, gated cardiac blood pools and capillary perfusion in brain and heart. Studies on patients with stroke and myocardial ischemia are also presented.
Date: January 1, 1978
Creator: Phelps, M.E.; Hoffman, E.J.; Huang, S.C.; Schelbert, H.R. & Kuhl, D.E.
Partner: UNT Libraries Government Documents Department

Recent developments in positron emission tomography (PET) instrumentation

Description: This paper presents recent detector developments and perspectives for positron emission tomography (PET) instrumentation used for medical research, as well as the physical processes in positron annihilation, photon scattering and detection, tomograph design considerations, and the potentials for new advances in detectors. 117 refs., 4 figs., 4 tabs.
Date: April 1, 1986
Creator: Derenzo, S.E. & Budinger, T.F.
Partner: UNT Libraries Government Documents Department

ECAT: a new computerized tomographic imaging system for position-emitting radiopharmaceuticals

Description: The ECAT was designed and developed as a complete computerized positron radionuclide imaging system capable of providing high contrast, high resolution, quantitative images in 2 dimensional and tomographic formats. Flexibility, in its various image mode options, allows it to be used for a wide variety of imaging problems.
Date: January 1, 1977
Creator: Phelps, M.E.; Hoffman, E.J.; Huang, S.C. & Kuhl, D.E.
Partner: UNT Libraries Government Documents Department