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Medical Radioisotope Data Survey: 2002 Preliminary Results

Description: A limited, but accurate amount of detailed information about the radioactive isotopes used in the U.S. for medical procedures was collected from a local hospital and from a recent report on the U.S. Radiopharmaceutical Markets. These data included the total number of procedures, the specific types of procedures, the specific radioisotopes used in these procedures, and the dosage administered per procedure. The information from these sources was compiled, assessed, pruned, and then merged into a single, comprehensive and consistent set of results presented in this report. (PIET-43471-TM-197)
Date: June 23, 2004
Creator: Siciliano, Edward R.
Partner: UNT Libraries Government Documents Department

DOE SBIR Phase I Grant No. DE-FG02-00ER83067, ''A Flexible and Economical Automated Nucleophilic [{sup 18}F]Fluorination synthesis System for PET Radiopharmaceuticals.'' Final Technical Report

Description: Phase I Final Report. A prototype manual remote synthesis system based on the unit operations approach was designed, constructed, and functionally tested. This general-purpose system was validated by its configuration and initial use for the preparation of the PET radiopharmaceutical [F-18]FLT using [F-18]fluoride ion.
Date: August 4, 2001
Creator: Padgett, Henry C.
Partner: UNT Libraries Government Documents Department

Rhenium Radioisotopes for Therapeutic Radiopharmaceutical Development

Description: The availability of therapeutic radioisotopes at reasonable costs is important for applications in nuclear medicine, oncology and interventional cardiology, Rhenium-186 (Re-186) and rhenium-1 88 (Re-188) are two reactor-produced radioisotope which are attractive for a variety of therapeutic applications, Rhenium-186 has a half-life of 90 hours and decays with emission of a &particle with a maximum energy of 1.08 MeV and a 135 keV (9Yo) gamma which permits imaging. In contrast, Re- 188 has a much shorter half-life of 16.9 hours and emits a p-particle with a much higher energy of 2.12 MeV (Em=) and a 155 keV gamma photon (15Yo) for imaging. While Re-186 is unavailable from a generator system and must be directly produced in a nuclear reactor, Re-188 can also be directly produced in a reactor with high specific activity, but is more conveniently and cost-effectively available as carrier-free sodium perrhenate by saline elution of the alumina-based tungsten-188 (W1 88)/Re-l 88 generator system [1-2]. Since a comprehensive overviewofRe-186 and Re-188 therapeutic agents is beyond the scope of this &tended Abstrac4 the goal is to provide key examples of various agents currently in clinical use and those which are being developed for important clinical applications.
Date: January 18, 1999
Creator: Beets, A.L.; Knapp, F.F., Jr.; Kropp, J.; Lin, W.-Y.; Pinkert, J. & Wang, S.-Y.
Partner: UNT Libraries Government Documents Department

Peptide Based Radiopharmaceuticals: Specific Construct Approach

Description: The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with <sup>99m</sup>Tc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures). In this approach, the biological function domain and the <sup>99m</sup>Tc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step <sup>99m</sup>Tc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 ┬ÁM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays RGD receptor with higher density. The results have indicated good diagnostic potential for their use in this clinical situation, as an imaging agent to ...
Date: October 21, 1997
Creator: Som, P; Rhodes, B A & Sharma, S S
Partner: UNT Libraries Government Documents Department

Receptor-targeted metalloradiopharmaceuticals. Final technical report

Description: Copper (II) and platinum (II) coordination complexes were prepared and characterized. These complexes were designed to afford structural homology with steroidal and non-steroidal estrogens for possible use as receptor-targeted radiopharmaceuticals. While weak affinity for the estrogen receptor was detectable, none would appear to have sufficient receptor-affinity for estrogen-receptor-targeted imaging or therapy.
Date: March 22, 2000
Creator: Green, Mark A.
Partner: UNT Libraries Government Documents Department

Molecular Engineering of Technetium and Rhenium Based Radiopharmaceuticals

Description: The research was based on the observation that despite the extraordinarily rich coordination chemistry of technetium and rhenium and several notable successes in reagent design, the extensive investigations by numerous research groups on a variety of N{sub 2}S{sub 2} and N{sub 3}S donor type ligands and on HYNIC have revealed that the chemistries of these ligands with Tc and Re are rather complex, giving rise to considerable difficulties in the development of reliable procedures for the development of radiopharmaceutical reagents.
Date: June 30, 2003
Creator: Zubieta, J.
Partner: UNT Libraries Government Documents Department

Radiopharmaceutical Tracers for Neural Progenitor Cells

Description: The Technical Report summarizes the results of the synthesis and microPET animal scanning of several compounds labeled with positron-emitting isotopes in normal, neonatal and kainic acid treated (seizure induced) rats as potential PET tracers to image the process of neurogenesis using positron emission tomography (PET). The tracers tested were 3'-deoxy-3'-[F-18]fluorothymidine ([F-18]FLT) and 5'-benzoyl-FTL, 1-(2'-deoxy-2'-[F-18]fluoro-B-D-arabinofuranosyl)-5-bromouracil (FBAU) and 3',5'-dibenzoyl-FBAU, N-[F-18]fluoroacetyl-D-glucosamine (FLAG) and tetraacetyl-FLAG, and L-[1-C-11]leucine.
Date: September 29, 2006
Creator: Mangner, Thomas J.
Partner: UNT Libraries Government Documents Department

Scoping assessment on medical isotope production at the Fast Flux Test Facility

Description: The Scoping Assessment addresses the need for medical isotope production and the capability of the Fast Flux Test Facility to provide such isotopes. Included in the discussion are types of isotopes used in radiopharmaceuticals, which types of cancers are targets, and in what way isotopes provide treatment and/or pain relief for patients.
Date: August 29, 1997
Creator: Scott, S.W.
Partner: UNT Libraries Government Documents Department

Ninth international symposium on radiopharmacology

Description: The goal of this Symposium is to provide a forum for those international scientists involved in applying the principles of pharmacology and radiation biology to the development of agents for the diagnosis and treatment of disease. The program will highlight state-of-the-art progress in the development of those agents used in conjunction with some form of radiation such as radiopharmaceuticals, radiopaques, photo- and radiosensitizing drugs, and neutron capture agents. An underlying pharmacokinetic parameter associated with all these agents is the need for site-specific delivery to an organ or tumor. Therefore, a major goal of the symposium will be to address those pharmacologic principles for targeting molecules to specific tissue sites. Accordingly, session themes will include receptor-mediated processes, membrane transporters, antibody interactions, metabolic trapping, and oligonucleotide-antisense mechanisms.
Date: December 31, 1995
Partner: UNT Libraries Government Documents Department

Radiation dose estimates for radiopharmaceuticals

Description: Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.
Date: April 1996
Creator: Stabin, M. G.; Stubbs, J. B. & Toohey, R. E.
Partner: UNT Libraries Government Documents Department

Frontiers in nuclear medicine symposium: Nuclear medicine & molecular biology

Description: This document contains the abstracts from the American College of Nuclear Physicians 1993 Fall Meeting entitled, `Frontiers in Nuclear Medicine Symposium: Nuclear Medicine and Molecular Biology`. This meeting was sponsored by the US DOE, Office of Health and Environmental Research, Office of Energy Research. The program chairman was Richard C. Reba, M.D.
Date: April 1, 1995
Partner: UNT Libraries Government Documents Department

Improving cancer treatment with cyclotron produced radionuclides. Comprehensive progress report, February 1, 1992--July 15, 1995

Description: This research continues the long term goals 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. This program fits into the nuclear medicine component of DOE`s mission, which is aimed at enhancing the beneficial applications of radiation, radionuclides, and stable isotopes in the diagnosis, study and treatment of human diseases. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology/Immunology; and Imaging Physics. An essential strategy is as follows: novel radionuclides and radiotracers developed in the Radiochemistry/Section under the DOE grant during the 1992--1995 will be employed in the Pharmacology/Immunology component in the period 1996--1999. Imaging Physics resolves relevant imaging related physics issues that arise during the experimentation that results. In addition to the basic research mission, this project also provides a basis for training of research scientists in radiochemistry, immunology, bioengineering and imaging physics.
Date: July 17, 1995
Creator: Larson, S.M. & Finn, R.D.
Partner: UNT Libraries Government Documents Department

Harvard-MIT research program in short-lived radiopharmaceuticals. Final report

Description: The Harvard-MIT Research Program in Short-lived Radiopharmaceuticals was established in 1977 to foster interaction among groups working in radiopharmaceutical chemistry at Harvard Medical School, the Massachusetts Institute of Technology, and the Massachusetts General Hospital. To this was added a group at The Childrens Hospital. From these collaborations and building upon the special strengths of the participating individuals, laboratories and institutions, it was hoped that original approaches would be found for the design of new, clinically useful, radiolabeled compounds. The original thrust of this proposal included: (a) examination of the coordination chemistry of technetium as a basis for rational radiopharmaceutical design, (b) development of an ultrashort-lived radionuclide generator for the diagnosis of congenital heart disease in newborns, (c) synthesis of receptor-site-directed halopharmaceuticals, (d) improved facile labeling of complex molecules with positron-emitting radionuclides. The authors` 1986 proposal was oriented toward organs and disease, emphasizing radiolabeled agents that delineate specific functions and the distribution of receptors in brain, heart, and tumors. In 1989, they further refined their purposes and focused on two major aims: (a) synthesis and utilization of neutral technetium and rhenium complexes of high specific activity, and (b) development of new approaches to the radiolabeling of proteins, peptides, immunoglobulins, and their fragments. In 1992, the authors amended this proposal to concentrate their efforts on biologically active peptides and proteins for targeted radiodiagnosis and therapy.
Date: February 1, 1995
Creator: Adelstein, S.J.
Partner: UNT Libraries Government Documents Department

Solution-reactor-produced Mo-99 using activated carbon to remore I-131

Description: The production of {sup 99}Mo in a solution reactor was explored. Activated charcoal was used to filter the {sup 131}I contaminant from an irradiated fuel solution. Gamma spectroscopy confirmed that the activated carbon trapped a significant amount of {sup 131}I, as well as notable amounts of {sup 133}Xe, {sup 105}Rb, and {sup 140}Ba; the carbon trapped a diminutive amount of {sup 99}Mo. The results promote the idea of solution-reactor-produced {sup 99}Mo. Solution reactors are favorable both energetically and environmentally. A solution reactor could provide enough {sup 99}Mo/{sup 99m}Te to support both the current and future radiopharmaceutical needs of the U.S.
Date: June 1, 1998
Creator: Kitten, S. & Cappiello, C.
Partner: UNT Libraries Government Documents Department

PRODUCTION OF RADIOACTIVE IODINE.

Description: Probably the most widely used cyclotron produced radiohalogen is I-123. It has gradually replaced I-131 as the isotope of choice for diagnostic radiopharmaceuticals containing radioiodine. It gives a much lower radiation dose to the patient and the gamma ray energy of 159 keV is ideally suited for use in a gamma camera. The gamma ray will penetrate tissue very effectively without excessive radiation dose. For this reason, it has in many instances replaced the reactor produced iodine-131 (Lambrecht and Wolf 1973). A great number of radiopharmaceuticals have been labeled using I-123 and the number is increasing. One of the most promising uses of I-123 is in the imaging of monoclonal antibodies to localize and visualize tumors. However, preclinical and clinical experiences with radiolabeled antibodies have not realized the expectations regarding specificity and sensitivity of tumor localization with these agents. It appears that much of the administered activity is not associated with the tumor site and only a small fraction actually accumulates there. Work continues in this area and tumor-associated antigens can be targets for specific antibody reagents.
Date: August 8, 2001
Creator: SCHLYER,D.J.
Partner: UNT Libraries Government Documents Department

Optimization of Dedicated Scintimammography Procedure Using Detector Prototypes and Compressible Phantoms

Description: Results are presented on the optimization of the design and use of dedicated compact scintimammography gamma cameras. Prototype imagers with a field-of-view (FOV) of 5 cm x 5 cm, 10 cm x 10 cm and 15 cm x 20 cm were used in either a dual modality mode as an adjunct technique to digital x-ray mammography imagers or as stand-alone instruments such as dedicated breast SPECT and planar imagers. Experimental data was acquired to select the best imaging modality (SPECT or planar) to detect small lesions using Tc{sup 99m} radio-labeled pharmaceuticals. In addition, studies were preformed to optimize the imaging geometry. Results suggest that the preferred imaging geometry is planar imaging with two opposing detector heads while the breast is under compression, however further study of the dedicated breast SPECT is warranted.
Date: October 1, 2000
Creator: Majewski, S.; Kieper, D.; Curran, E.; Keppel, C.; Kross, B.; Palumbo, A. et al.
Partner: UNT Libraries Government Documents Department

PRODUCTION CONSIDERATIONS FOR THE CLASSICAL PET NUCLIDES.

Description: Nuclear Medicine is the specialty of medical imaging, which utilizes a variety of radionuclides incorporated into specific compounds for diagnostic imaging and therapeutic applications. During recent years, research efforts associated with this discipline have concentrated on the decay characteristics of particular radionuclides and the design of unique radiolabeled tracers necessary to achieve time-dependent molecular images. The specialty is expanding with specific Positron emission tomography (PET) and SPECT radiopharmaceuticals allowing for an extension from functional process imaging in tissue to pathologic processes and nuclide directed treatments. PET is an example of a technique that has been shown to yield the physiologic information necessary for clinical oncology diagnoses based upon altered tissue metabolism. Most PET drugs are currently produced using a cyclotron at locations that are in close proximity to the hospital or academic center at which the radiopharmaceutical will be administered. In November 1997, a law was enacted called the Food and Drug Administration Modernization Act of 1997 which directed the Food and Drug Administration (FDA) to establish appropriate procedures for the approval of PET drugs in accordance with section 505 of the Federal Food, Drug, and Cosmetic Act and to establish current good manufacturing practice requirements for such drugs. At this time the FDA is considering adopting special approval procedures and cGMP requirements for PET drugs. The evolution of PET radiopharmaceuticals has introduced a new class of ''drugs'' requiring production facilities and product formulations that must be closely aligned with the scheduled clinical utilization. The production of the radionuclide in the appropriate synthetic form is but one critical component in the manufacture of the finished radiopharmaceutical.
Date: June 25, 2001
Creator: Finn, R. & Schlyer, D.
Partner: UNT Libraries Government Documents Department

Project definition study for the National Biomedical Tracer Facility

Description: The University of Alabama at Birmingham (UAB) has conducted a study of the proposed National Biomedical Tracer Facility (NBTF). In collaboration with General Atomics, RUST International, Coleman Research Corporation (CRC), IsoMed, Ernst and Young and the advisory committees, they have examined the issues relevant to the NBTF in terms of facility design, operating philosophy, and a business plan. They have utilized resources within UAB, CRC and Chem-Nuclear to develop recommendations on environmental, safety and health issues. The Institute of Medicine Panel`s Report on Isotopes for Medicine and the Life Sciences took the results of prior workshops further in developing recommendations for the mission of the NBTF. The IOM panel recommends that the NBTF accelerator have the capacity to accelerate protons to 80 MeV and a minimum of 750 microamperes of current. The panel declined to recommend a cyclotron or a linac. They emphasized a clear focus on research and development for isotope production including target design, separation chemistry and generator development. The facility needs to emphasize education and training in its mission. The facility must focus on radionuclide production for the research and clinical communities. The formation of a public-private partnership resembling the TRIUMF-Nordion model was encouraged. An advisory panel should assist with the NBTF operations and prioritization.
Date: February 15, 1995
Creator: Roozen, K.
Partner: UNT Libraries Government Documents Department

A workshop on developing risk assessment methods for medical use of radioactive material. Volume 2: Supporting documents

Description: A workshop was held at the Idaho National Engineering Laboratory, August 16--18, 1994 on the topic of risk assessment on medical devices that use radioactive isotopes. Its purpose was to review past efforts to develop a risk assessment methodology to evaluate these devices, and to develop a program plan and a scoping document for future methodology development. This report contains presentation material and a transcript of the workshop. Participants included experts in the fields of radiation oncology, medical physics, risk assessment, human-error analysis, and human factors. Staff from the US Nuclear Regulatory Commission (NRC) associated with the regulation of medical uses of radioactive materials and with research into risk-assessment methods participated in the workshop. The workshop participants concurred in NRC`s intended use of risk assessment as an important technology in the development of regulations for the medical use of radioactive material and encouraged the NRC to proceed rapidly with a pilot study. Specific recommendations are included in the executive summary and the body of this report.
Date: August 1995
Creator: Tortorelli, J. P.
Partner: UNT Libraries Government Documents Department

A workshop on developing risk assessment methods for medical use of radioactive material. Volume 1: Summary

Description: A workshop was held at the Idaho National Engineering Laboratory, August 16--18, 1994 on the topic of risk assessment on medical devices that use radioactive isotopes. Its purpose was to review past efforts to develop a risk assessment methodology to evaluate these devices, and to develop a program plan and a scoping document for future methodology development. This report contains a summary of that workshop. Participants included experts in the fields of radiation oncology, medical physics, risk assessment, human-error analysis, and human factors. Staff from the US Nuclear Regulatory Commission (NRC) associated with the regulation of medical uses of radioactive materials and with research into risk-assessment methods participated in the workshop. The workshop participants concurred in NRC`s intended use of risk assessment as an important technology in the development of regulations for the medical use of radioactive material and encouraged the NRC to proceed rapidly with a pilot study. Specific recommendations are included in the executive summary and the body of this report. An appendix contains the 8 papers presented at the conference: NRC proposed policy statement on the use of probabilistic risk assessment methods in nuclear regulatory activities; NRC proposed agency-wide implementation plan for probabilistic risk assessment; Risk evaluation of high dose rate remote afterloading brachytherapy at a large research/teaching institution; The pros and cons of using human reliability analysis techniques to analyze misadministration events; Review of medical misadministration event summaries and comparison of human error modeling; Preliminary examples of the development of error influences and effects diagrams to analyze medical misadministration events; Brachytherapy risk assessment program plan; and Principles of brachytherapy quality assurance.
Date: August 1, 1995
Creator: Tortorelli, J.P.
Partner: UNT Libraries Government Documents Department

Development of Reagents for Application of At-211 to Targeted Radionuclide Therapy of Cancer

Description: This grant covered only a period of 4 months as the major portion of the award was returned to DOE due to an award of funding from NIH that covered the same research objectives. A letter regarding the termination of the research is attached as the last page of the Final Report. The research conducted was limited due to the short period of this grant, but the results obtained in that period are outlined in the Final Report. The studies addressed in the research effort were directed at a problem that is of critical importance to the in vivo application of the alpha-particle emitting radionuclide At-211. That problem, low in vivo stability of many astatinated molecules, severely limits the use of At-211 in therapeutic applications. The advances sought in the studies were expected to expand the types of biomolecules that can be used as carriers of At-211, and provide improved in vivo targeting of the radiation dose compared with the dose delivered to normal tissue.
Date: December 23, 2011
Creator: Wilbur, D. Scott
Partner: UNT Libraries Government Documents Department

Radiopharmaceutical and Gene Therapy Program

Description: The objective of our research program was to determine whether novel receptors can be induced in solid cancers as a target for therapy with radiolabeled unmodified peptides that bind to the receptors. The hypothesis was that induction of a high number of receptors on the surface of these cancer cells would result in an increased uptake of the radiolabeled monomeric peptides as compared to published results with radiolabeled antibodies or peptides to naturally expressed antigens or receptors, and therefore a better therapeutic outcome. The following is a summary of published results.
Date: February 9, 2006
Creator: Buchsbaum, Donald J.
Partner: UNT Libraries Government Documents Department