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Drug Enforcement in the United States: History, Policy, and Trends

Description: This report reviews federal domestic drug enforcement. First, it provides a history and background of drug enforcement in the United States including how drugs came under the control of federal justice authorities and how legislation and administrative actions changed domestic drug enforcement. It then provides a brief overview of drug enforcement in the United States and summarizes U.S. drug policy. Finally, the report presents trends in federal drug enforcement and concludes with a discussion of drug enforcement issues going forward.
Date: October 2, 2014
Creator: Sacco, Lisa N.
Partner: UNT Libraries Government Documents Department

Safe and Drug-Free Schools and Communities Act: Program Overview and Reauthorization Issues

Description: This report provides information on the Safe and Drug-Free Schools and Communities Act (SDFSCA), the federal government's major initiative to prevent drug abuse and violence in and around schools, and its support for two major grant programs: one for states and one for National Activities. The report also discusses issues of reauthorization for the SDFSCA following the Virginia Tech tragedy, and issues of potential concern to Members of Congress. It includes the Administration's proposal, the recommendations of the Safe and Drug-Free Schools and Communities Act Advisory Board, the recommendations of the Secretaries of the U.S. Department of Education (ED), the U.S. Department of Health and Human Services (HHS), and the U.S. Department of Justice (DOJ), following the Virginia Tech tragedy, and issues of potential concern to Members of Congress. (Summay).
Date: May 19, 2008
Creator: McCallion, Gail
Partner: UNT Libraries Government Documents Department

Compounded Drugs

Description: This report provides background information on compounded drugs (CDs) and nontraditional compounding pharmacies relevant to policy discussions. This includes an overview of the 2012 fungal meningitis outbreak; recent recalls of compounded drugs; definitions of traditional compounding and nontraditional compounding; information on the CDs produced and by whom; information on the demand for nontraditional compounding, including the role of shortages of sterile injectable drugs, hospital outsourcing, and patient and provider demand; and information on adverse events involving compounded drugs.
Date: May 23, 2013
Creator: Glassgold, Judith M.
Partner: UNT Libraries Government Documents Department

Animal Drug User Fee Programs

Description: This report discusses aspects of the Animal Drug User Fee Act of 2003 (ADUFA I), including funding and program performance; the Food and Drug Administration's (FDA) ADUFA II and Animal Generic Drug User Fee Act of 2008 (AGDUFA) proposals; congressional activity; and other relevant issues.
Date: August 4, 2008
Creator: Lister, Sarah A.
Partner: UNT Libraries Government Documents Department

Evaluation of few-view reconstruction parameters for illicit substance detection using fast-neutron transmission spectroscopy

Description: We have evaluated the performance of the Maximum Likelihood algebraic reconstruction algorithm for the case of a few projections and for relatively coarse projection and pixel resolution. Ibis evaluation was done using receiver operator curves obtained from the fast neutron transmission spectroscopy system operated in a mode to detect explosives in luggage. The results show that increasing the number of projection angles is more important than increasing the projection resolution, the reconstructed pixel resolution, or the number of iterations in the Maximum Likelihood algorithm. A 100% detection efficiency with essentially no false positives is possible for a square block of RDX explosive, a projection resolution of 2 cm, a reconstructed pixel size of 2 {times} 2 cm, and five projection angles. For rectangular shaped explosives more angles are required obtain the same system performance.
Date: December 31, 1995
Creator: Fink, C.L.; Humm, P.G. & Micklich, B.J.
Partner: UNT Libraries Government Documents Department

Pharmaceutical Patent Litigation Settlements: Implications for Competition and Innovation

Description: This report introduces and analyzes innovation policy issues concerning pharmaceutical patent litigation settlements, including pharmaceutical patent litigation procedures under the Hatch-Waxman Act, the concept of reverse payment settlements, the status of reverse payment settlements under the antitrust laws, and congressional issues and alternatives.
Date: November 4, 2008
Creator: Thomas, John R.
Partner: UNT Libraries Government Documents Department

Advances in associated-particle sealed-tube neutron probe diagnostics for substance detection

Description: The development and investigation of a small associated-particle sealed-tube neutron generator (APSTNG) shows potential to allow the associated-particle diagnostic method to be moved out of the laboratory into field applications. The APSTNG interrogates the inspected object with 14-MeV neutrons generated from the deuterium-tritium reaction and detects the alpha-particle associated with each neutron inside a cone encompassing the region of interest. Gamma-ray spectra of resulting neutron reactions identify many nuclides. Flight-times determined from detection times of the gamma-rays and alpha-particles can yield a separate coarse tomographic image of each identified nuclide, from a single orientation. Chemical substances are identified by comparing relative spectral line intensities with ratios of elements in reference compounds. The high-energy neutrons and gamma-rays penetrate large objects and dense materials. Generally no collimators or radiation shielding are needed. Proof-of-concept laboratory experiments have been successfully performed for simulated nuclear, chemical warfare, and conventional munitions. Most recently, inspection applications have been investigated for radioactive waste characterization, presence of cocaine in propane tanks, and uranium and plutonium smuggling. Based on lessons learned with the present APSTNG system, an advanced APSTNG tube (along with improved high voltage supply and control units) is being designed and fabricated that will be transportable and rugged, yield a substantial neutron output increase, and provide sufficiently improved lifetime to allow operation at more than an order of magnitude increase in neutron flux.
Date: July 1, 1995
Creator: Rhodes, E.; Dickerman, C.E. & Frey, M.
Partner: UNT Libraries Government Documents Department

Low-Charge State AMS for High Throughput 14C Quantification

Description: Accelerator mass spectrometry (AMS) quantifies attomole (10{sup -18}) amounts of {sup 14}C in milligram sized samples. This sensitivity is used to trace nutrients, toxins and therapeutics in humans and animals at less than {micro}g/kg doses containing 1-100 nCi of {sup 14}C. Widespread use of AMS in pharmaceutical development and biochemical science has been hampered by the size and expense of the typical spectrometer that has been developed for high precision radiocarbon dating. The precision of AMS can be relaxed for biochemical tracing, but sensitivity, accuracy and throughput are important properties that must be maintained in spectrometers designed for routine quantification. We are completing installation of a spectrometer that will maintain the high throughput of our primary spectrometer but which requires less than 20% of the floor space and of the cost. Sensitivity and throughput are kept high by using the LLNL intense cesium sputter ion source with solid graphitic samples. Resultant space-charge effects are minimized by careful modeling to find optimal ion transport in the spectrometer. A long charge-changing ''stripper gas'' volume removes molecular isobars at potentials of a few hundred kiloVolts, reducing the size of the accelerating component. Fast ion detectors count at high rates to keep a wide dynamic range for 14 C concentrations. Solid sample presentation eliminates the sample cross contamination that degrades accuracy and the effects of ''memory'' in the ion source. Automated processes are under development for conversion of liquid and solid biological samples to the preferred graphitic form for the ion source.
Date: June 16, 2000
Creator: Ognibene, T. J.; Roberts, M. L.; Southon, J. R. & Vogel, J. S.
Partner: UNT Libraries Government Documents Department

Measurement of photodynamic therapy drug concentrations in a tissue

Description: This is the final report of a one-year laboratory-directed research and development project at the Los Alamos National Laboratory (LANL). Photodynamic therapy (PDT) is an experimental treatment modality for cancer in which a photoactive molecule with an affinity for tumors in administered to the patient, then excited by light. Photoactivation creates singlet oxygen consequently killing the tissue. Knowledge of the concentration of the photoactive compound in the tissue is necessary for proper light dosimetry during PDT. Presently, the control of light application is problematic. If too much light is applied, damage to the surrounding tissue will occur. If insufficient light is applied, the targeted tissue volume will remain viable. The ideal implementation of PDT would use a feedback system for light delivery that incorporates the optical properties of the tissue and knowledge of the concentration of the photoactive compound. This project sought to develop a method for measuring photosensitizer concentrations in tissue phantoms that will lead to a noninvasive, endoscopically compatible, in vivo method of measuring PST drug concentrations.
Date: September 1, 1996
Creator: Mourant, J.; Biglo, I. & Johnson, T.
Partner: UNT Libraries Government Documents Department

Electronic aroma detection technology for forensic and law enforcement applications

Description: A major problem hindering criminal investigations is the lack of appropriate tools for proper crime scene investigations. Often locating important pieces of evidence means relying on the ability of trained detection canines. Development of analytical technology to uncover and analyze evidence, potentially at the scene, could serve to expedite criminal investigations, searches, and court proceedings. To address this problem, a new technology based on gas sensor arrays was investigated for its applicability to forensic and law enforcement problems. The technology employs an array of sensors that respond to volatile chemical components yielding a characteristic `fingerprint` pattern representative of the vapor- phase composition of a sample. Sample aromas can be analyzed and identified using artificial neural networks that are trained on known aroma patterns. Several candidate applications based on known technological needs of the forensic and law enforcement communities have been investigated. These applications have included the detection of aromas emanating from cadavers to aid in determining time since death, drug detection for deterring the manufacture, sale, and use of drugs of abuse, and the analysis of fire debris for accelerant identification. The results to date for these applications have been extremely promising and demonstrate the potential applicability of this technology for forensic use.
Date: December 31, 1996
Creator: Barshick, S.-A.; Griest, W.H. & Vass, A.A.
Partner: UNT Libraries Government Documents Department

Simultaneous two-photon excitation of photodynamic therapy agents

Description: The spectroscopic and photochemical properties of several photosensitive compounds are compared using conventional single-photon excitation (SPE) and simultaneous two-photon excitation (TPE). TPE is achieved using a mode-locked titanium:sapphire laser, the near infrared output of which allows direct promotion of non-resonant TPE. Excitation spectra and excited state properties of both type 1 and type 2 photodynamic therapy (PDT) agents are examined.
Date: January 1, 1998
Creator: Wachter, E.A.; Fisher, W.G.; Partridge, W.P.; Dees, H.C. & Petersen, M.G.
Partner: UNT Libraries Government Documents Department

[3H]Azidodantrolene photoaffinity labeling, synthetic domain peptides and monoclonal antibody reactivity identify the dantrolene binding sequence on RyR1

Description: Dantrolene is a drug that suppresses intracellular Ca2+ release from sarcoplasmic reticulum in normal skeletal muscle and is used as a therapeutic agent in individuals susceptible to malignant hyperthermia. Though its precise mechanism of action has not been elucidated, we have identified the N-terminal region (amino acids 1-1400) of the skeletal muscle isoform of the ryanodine receptor (RyR1), the primary Ca2+ release channel in sarcoplasmic reticulum, as a molecular target for dantrolene using the photoaffinity analog [3H]azidodantrolene(1). Here, we demonstrate that heterologously expressed RyR1 retains its capacity to be specifically labeled with [3H]azidodantrolene,indicating that muscle specific factors are not required for this ligand-receptor interaction. Synthetic domain peptides of RyR1, previously shown to affect RyR1 function in vitro and in vivo, were exploited as potential drug binding site mimics and used in photoaffinity labeling experiments. Only DP1 and DP1-2, peptide s containing the amino acid sequence corresponding to RyR1 residues 590-609, were specifically labeled by [3H]azidodantrolene. A monoclonal anti-RyR1 antibody which recognizes RyR1 and its 1400 amino acid N-terminal fragment, recognizes DP1 and DP1-2 in both Western blots and immunoprecipitation assays, and specifically inhibits [3H]azidodantrolene photolabeling of RyR1 and its N-terminal fragment in sarcoplasmic reticulum. Our results indicate that synthetic domain peptides can mimic a native, ligand binding conformation in vitro, and that the dantrolene binding site and the epitope for the monoclonal antibody on RyR1 are equivalent and composed of amino-acids 590-609.
Date: June 14, 2002
Creator: Paul-Pletzer, Kalanethee; Yamamoto, Takeshi; Bhat, Manju B.; Ma, Jianjie; Ikemoto, Noriaki; Jimenez, Leslie S. et al.
Partner: UNT Libraries Government Documents Department

Profile of the chemicals industry in California: Californiaindustries of the future program

Description: The U.S. Department of Energy (DOE) Office of Industrial Technologies (OIT) established the Industries of the Future (IOF) program to increase energy efficiency, reduce waste production and to improve competitiveness, currently focusing on nine sectors. The IOF is a partnership strategy involving industry, the research community and the government, working together to identify technology needs, promote industrial partnerships and implement joint measures with all partners involved. The State Industries of the Future (SIOF) program delivers the accomplishments of the national Industries of the Future strategy to the local level, to expand the technology opportunities to a larger number of partners and reach smaller businesses and manufacturers that were not initially involved in the IOF effort. The state programs bring together industry, academia, and state agencies to address the important issues confronting industry in the state. These public-private coalitions facilitate industry solutions locally and enhance economic development. California has started a State Industries of the Future effort, in collaboration with the U.S. Department of Energy. The California Energy Commission (CEC) is leading the SIOF program in California, as part of many other programs to improve the energy efficiency and performance of industries in California. The California State IOF program aims to build a network of participants from industry, academia and government in four selected industrial sectors as a basis for the development of a strategic partnership for industrial energy efficient technology in the state. In California the IOF effort focuses petroleum refining, chemical processing, food processing and electronics. As part of this effort, the SIOF program will develop roadmaps for technology development for the selected sectors. On the basis of the roadmap, the program will develop successful projects with co-funding from state and federal government, and promote industry-specific energy-efficiency. An important element of the SIOF-program is the preparation of R&D roadmaps ...
Date: June 1, 2004
Creator: Galitsky, Christina & Worrell, Ernst
Partner: UNT Libraries Government Documents Department

Development of an energy conservation voluntary agreement pilot project in the steel sector in Shandong

Description: China faces a significant challenge in the years ahead to continue to provide essential materials and products for a rapidly-growing economy while addressing pressing environmental concerns. Energy is a fundamental element of the national economy and the conditions of its use have a direct impact on China's ability to reach its sustainable development goals. China's industrial sector, which accounts for over 70 percent of the nation's total energy consumption each year, provides materials such as steel and cement that build the nation's roads, bridges, homes, offices and other buildings. Industrial products include bicycles, cars, buses, trains, ships, office equipment, appliances, furniture, packaging, pharmaceuticals, and many other components of everyday life in an increasingly modern society. This vital production of materials and products, however, comes with considerable problems. China's industrial sector is heavily dependent on the country's abundant, yet polluting, coal resources. Industrial production locally pollutes the air with emissions of particulates, carbon monoxide, sulfur dioxide, and nitrogen oxides, uses scarce water and oil resources, emits greenhouse gases contributing to the warming global atmosphere, and often produces hazardous and polluting wastes. Fostering innovative approaches to reduce the use of polluting energy resources and to diminish pollution from industrial production that are tailored to China's emerging market-based economy is one of the most important challenges facing the nation today. The pressures of rapid industrial production growth, continued environmental degradation, and increased competition create a situation that calls for a strategically-planned evolution of China's industries into world-class production facilities that are competitive, energy-efficient and less polluting. Such a transition requires the complete commitment of industrial enterprises and the government to work together to transform the industrial facilities of China. Internationally, such a transformation of the industrial sector has been realized in a number of countries using an innovative policy mechanism called Voluntary Agreements. ...
Date: February 5, 2004
Creator: Price, Lynn; Yun, Jiang; Worrell, Ernst; Wenwei, Du & Sinton, Jonathan E.
Partner: UNT Libraries Government Documents Department

Market transformation lessons learned from an automated demand response test in the Summer and Fall of 2003

Description: A recent pilot test to enable an Automatic Demand Response system in California has revealed several lessons that are important to consider for a wider application of a regional or statewide Demand Response Program. The six facilities involved in the site testing were from diverse areas of our economy. The test subjects included a major retail food marketer and one of their retail grocery stores, financial services buildings for a major bank, a postal services facility, a federal government office building, a state university site, and ancillary buildings to a pharmaceutical research company. Although these organizations are all serving diverse purposes and customers, they share some underlying common characteristics that make their simultaneous study worthwhile from a market transformation perspective. These are large organizations. Energy efficiency is neither their core business nor are the decision makers who will enable this technology powerful players in their organizations. The management of buildings is perceived to be a small issue for top management and unless something goes wrong, little attention is paid to the building manager's problems. All of these organizations contract out a major part of their technical building operating systems. Control systems and energy management systems are proprietary. Their systems do not easily interact with one another. Management is, with the exception of one site, not electronically or computer literate enough to understand the full dimensions of the technology they have purchased. Despite the research team's development of a simple, straightforward method of informing them about the features of the demand response program, they had significant difficulty enabling their systems to meet the needs of the research. The research team had to step in and work directly with their vendors and contractors at all but one location. All of the participants have volunteered to participate in the study for altruistic reasons, ...
Date: August 1, 2004
Creator: Shockman, Christine; Piette, Mary Ann & ten Hope, Laurie
Partner: UNT Libraries Government Documents Department

Fitness for duty in the nuclear power industry. Annual summary of program performance reports

Description: This report summarizes the data from the semiannual reports on fitness-for-duty programs submitted to the NRC by utilities for two reporting periods: January 1-June 30, 1995, and July 1 -December 31, 1995. During 1995, licensees reported that they had conducted 150,121 tests for the presence of illegal drugs and alcohol. Of these tests, 1,476 (.98%) were confirmed positive. The majority of positive test results (1, 122) were obtained through pre-access testing. Of tests conducted on workers having access to the protected area, there were 180 positive tests from random testing and 139 positive tests from for-cause testing. Follow-up testing of workers who had previously tested positive resulted in 35 positive tests. For-cause testing resulted in the highest percentage of positive tests; about 18 percent of for-cause tests were positive. This compares with a positive test rate of 1.41 percent of pre-access tests and .27 percent of random tests. The positive test rate for workers with unescorted access was .50 percent. Positive test rates also varied by category of worker. When all types of tests are combined, short-term contractor personnel had the highest positive test rate at 1.44 percent. Licensee employees and long-term contractors had lower combined positive test rates (.34% and .40%, respectively). Of the substances tested, marijuana was responsible for the highest percentage of positive test results (53.08%), followed by cocaine (24.24%) and alcohol (17.17%). The overall positive test rate for 1995 (.98%) was higher than in 1994 (.84%). Several factors had an impact on the positive test rate across test categories for 1994 and 1995 compared to previous years. These factors include the NRC`s reduction in the mandatory random testing rate from 100 percent to 50 percent, effective in 1994, and initiatives by licensees such as lowered marijuana screening cutoff levels and reported improvements in licensees ability to ...
Date: July 1996
Creator: Silbernagel, M.; Brichoux, J. & Durbin, N.
Partner: UNT Libraries Government Documents Department

Fitness for duty in the nuclear power industry: Annual summary of program performance reports CY 1994. Volume 5

Description: This report summarizes the data from the semiannual reports on fitness-for-duty programs submitted to the NRC by utilities for two reporting periods: January 1 through June 30, 1994, and July I through December 31, 1994. During 1994, licensees reported that they had conducted 163,241 tests for the presence of illegal drugs and alcohol. Of these tests, 1,372 (.84%) were confirmed positive. Positive test results varied by category of test and category of worker. The majority of positive test results (977) were obtained through pre-access testing. Of tests conducted on workers having access to the protected area, there were 223 positive tests from random testing and 122 positive tests from for-cause testing. Follow-up testing of workers who had previously tested positive resulted in 50 positive tests. For-cause testing resulted in the highest percentage of positive tests; about 16 percent of for-cause tests were positive. This compares with a positive test rate of 1.22 percent of pre-access tests and .28 percent of random tests. The positive test rate for badged workers (including only random, for-cause, and follow-up test results) was .48 percent. Positive test rates also varied by category of worker. When all types of tests are combined (pre-access, random, for-cause, and follow-up testing), short-term contractor personnel had the highest positive test rate at 1.22 percent. Licensee employees and long-term contractors had lower combined positive test rates (.33% and .49%, respectively). Of the substances tested, marijuana was responsible for the highest percentage of positive test results (52.07%), followed by cocaine (24.25%) and alcohol (17.45%).
Date: August 1995
Creator: Westra, C.; Durbin, N. & Field, I.
Partner: UNT Libraries Government Documents Department

Magnetically responsive microparticles for targeted drug and radionuclide delivery.

Description: We are currently investigating the use of magnetic particles--polymeric-based spheres containing dispersed magnetic nanocrystalline phases--for the precise delivery of drugs via the human vasculature. According to this review, meticulously prepared magnetic drug targeting holds promise as a safe and effective method of delivering drugs to specific organ, tissue or cellular targets. We have critically examined the wide range of approaches in the design and implementation of magnetic-particle-based drug delivery systems to date, including magnetic particle preparation, drug encapsulation, biostability, biocompatibility, toxicity, magnetic field designs, and clinical trials. However, we strongly believe that there are several limitations with past developments that need to be addressed to enable significant strides in the field. First, particle size has to be carefully chosen. Micrometer-sized magnetic particles are better attracted over a distance than nanometer sized magnetic particles by a constant magnetic field gradient, and particle sizes up to 1 {micro}m show a much better accumulation with no apparent side effects in small animal models, since the smallest blood vessels have an inner diameter of 5-7 {micro}m. Nanometer-sized particles <70 nm will accumulate in organ fenestrations despite an effective surface stabilizer. To be suitable for future human applications, our experimental approach synthesizes the magnetic drug carrier according to specific predefined outcome metrics: monodisperse population in a size range of 100 nm to 1.0 {micro}m, non-toxic, with appropriate magnetic properties, and demonstrating successful in vitro and in vivo tests. Another important variable offering possible improvement is surface polarity, which is expected to prolong particle half-life in circulation and modify biodistribution and stability of drugs in the body. The molecules in the blood that are responsible for enhancing the uptake of particles by the reticuloendothelial system (RES) prefer to associate with hydrophobic surfaces. Accordingly, we will tackle this challenge by modifying the particles with hydrophilic coatings such ...
Date: February 16, 2004
Creator: Kaminski, M. D.; Ghebremeskel, A. N.; Nunez, L.; Kasza, K. E.; Chang, F.; Chien, T.-H. et al.
Partner: UNT Libraries Government Documents Department

A new proof-of-principle contraband detection system

Description: A new concept for a CDS has been developed under a Phase I ARPA funded program; it uses gamma resonance absorption (GRA) to detect certain illegal drugs that may be transported in man-portable containers. A high detection probability for heroin and cocaine is possible with a device that is also searching for explosives. Elemental detection of both N and Cl is utilized, and with tomography, a 3D density image of the elements is generated. Total density image is also developed. These two together may be used with considerable confidence in determining if heroin or cocaine is present in the interrogated containers in a small quantity (1 kg). The CDS employs a high current ({ge}10 mA) DC accelerator that produces a beam of 1.75 or 1.89 MeV protons. These protons impact a target with coatings of {sup 13}C and {sup 34}S. Depending on the coating, the resultant resonant gamma rays are preferentially absorbed in either {sup 14}N or {sup 35}Cl. The resonant gammas come off the target in a conical fan at 80.7{degree} for N and 82{degree} for Cl; a common array of segmented BGO detectors is used over an arc of 53{degree} to provide input to an imaging subsystem. The tomography makes use of rotation and vertical translation of a baggage carousel holding typically 18 average sized bags for batch processing of the contents. The single proton accelerator and target can supply multiple detection stations with the appropriate gammas, a feature that may lead to very high throughput potential approaching 2000 bags/hr. Each detection station can operate somewhat independently from the others. This paper presents the overall requirements, design, operating principles, and characteristics of the CDS proof-of-principle device developed in the Phase I program.
Date: December 1, 1995
Creator: Sredniawski, J.J.; Debiak, T.; Kamykowski, E.; Rathke, J.; Schmor, P.; Altman, A. et al.
Partner: UNT Libraries Government Documents Department

Pharmaceutical Patent Litigation Settlements: Implications for Competition and Innovation

Description: This report introduces and analyzes innovation policy issues concerning pharmaceutical patent litigation settlements, including pharmaceutical patent litigation procedures under the Hatch-Waxman Act, the concept of reverse payment settlements, the status of reverse payment settlements under the antitrust laws, and congressional issues and alternatives.
Date: January 20, 2011
Creator: Thomas, John R.
Partner: UNT Libraries Government Documents Department

Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation

Description: The NMDA receptor has been implicated in neuronal death following stroke, brain injury and neurodegenerative disorders (e.g. Alzheimer's, Parkinson's and Huntington's disease) and in physiological functions (e.g. memory and cognition). Non-competitive antagonists, such as MK- 801 and CNS-1102, that block the action of glutamate at the NMDA receptor have been shown to be neuroprotective by blocking the influx of calcium into the cells. As a result, they are being considered as therapeutic agents for the above mentioned diseases. Several Fluorine-containing novel analogs of NMDA channel blockers have been synthesized and evaluated in search of a compound suitable for 18F labeling and Positron Emission Tomography (PET). Based on in vitro binding assay studies on rat brain membranes, the novel compounds examined displayed a range of affinities. Preliminary analyses indicated that chlorine is the best halogen on the ring, and that ethyl fluoro derivatives are more potent than methyl-fluoro compounds. Further analysis based on autoradiography will be needed to examine the regional binding characteristics of the novel compounds examined in this study. Labeling with 18F will allow the use of these compounds in humans, generating new insights into mechanisms and treatment of diseases involving malfunction of the glutamatergic system in the brain.
Date: January 1, 2001
Creator: Alvarado, M. & Biegon, A.
Partner: UNT Libraries Government Documents Department

Characterization of Tumor-Avid Antibody Fragments Genetically Engineered for Mono-Specific Radionuclide Chelation

Description: The successful clinical application of targeted-radiopharmaceuticals depends on the development of molecules that optimize tumor specific radionuclide deposition and minimize non-specific organ irradiation. To this end, this proposal outlines a research effort to identify and evaluate novel antibodies and antibody fragments that bind breast tumors. The tumor-avid antibodies will be investigated for as imaging and therapeutic agents and to gain a better understanding of the pharmacokinetics and metabolism of radiolabeled tumor-avid antibody fragments through the use of site-specifically labeled molecules. Antibodies or antibody fragments, that bind breast carcinoma carbohydrate antigens, will be obtained from hybridoma or bacteriophage library screening. More specifically, antibody fragments that bind the carcinoma-associated Thomsen-Friedenreich (T) antigen will be radiolabeled with {sup 99m}Tc and {sup 188}Re at a natural amino acid chelation site and will be investigated in vivo for their abilities to target human breast tumors. In addition, site-specific radiolabeled antibody fragments will be biosynthesized using misacylated suppressor tRNAs. Homogeneously radiolabeled populations of antibody fragments will be used to investigate the effects of radionuclide location and chelation chemistries on their biodistribution and metabolism. It is hypothesized that site-specifically radiolabeled antibody fragments will possess enhanced tumor imaging and therapeutic properties due to optimal label location and conjugation chemistries. New insights into the factors that govern antibody metabolism in vivo are also expected from this work. Results from these studies should enhance our ability to design and synthesize radiolabeled antibody fragments that have improved pharmacokinetic properties. The studies in this proposal involve basic research into the development of antibody-based radiopharmaceuticals, with the ultimate goal of application in humans. This type of basic nuclear medicine research has been funded by the Department of Energy and is consistent with the research topics and guidelines recommended during the recent review of the Medical Applications and Biophysical Research Program.
Date: December 31, 2003
Creator: Quinn, T.P.
Partner: UNT Libraries Government Documents Department