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Biomedical subjects

Joseph C Hung

Publications and source records attributed to Joseph C Hung.

16 recordsLinked to original sources
PubMed2005

A cost-effective and versatile xenon gas dispenser.

OBJECTIVE: To modify a commercial xenon gas dispenser so that two xenon unit-dose vials could be combined with a modified dispenser to deliver a recommended dose. METHOD: To maintain the same operating mechanism, changes were made only to the vial shield and the needle port of the original gas dispenser. The modified gas dispenser consisted of two puncture needles and two vial holders shielded with the same thickness of lead as the commercial dispenser. RESULTS: Our evaluation showed that the modified gas dispenser operated the same way as the commercial unit, and the average 133Xe residual activity in either one or two xenon unit-dose vials of the modified gas dispenser was not significantly different from that in one vial of the commercial xenon gas dispenser. CONCLUSION: The modified xenon gas dispenser allows the stock of xenon gas vials to be managed cost-effectively. The modified unit can be used to dispense two low-activity xenon gas vials to deliver a standard dose to a patient. Also, the modified gas dispenser can be used to combine different amounts of xenon activity in two unit-dose vials in order to customize the dose delivered to patients with special needs (e.g., obese patients). Our modified device can also function as a single-dose dispenser by placing an empty vial alongside the unit-dose vial of radioactive xenon gas.

Administration, Inhalation↗
PubMed2005

Inhibition evaluation for a 20-min endotoxin limit test on FDG.

OBJECTIVES: In chemical quality control tests for 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG), gel time is inversely related to endotoxin concentration. Solutions for positive product control (PPC) and positive water control (PWC) should contain a highly concentrated endotoxin level. The aims of our study were to derive an endotoxin concentration that causes PPC and PWC to gel and to evaluate inhibitory effects caused by FDG on gel formation in PPC and PWC test solutions. METHODS: At expiration, the maximum administered total dose (in millilitres) of FDG should contain fewer than 175 endotoxin units (EU). Our average batch volume of FDG is 15 ml; thus, the minimum endotoxin limit should be 12 EU x ml(-1) . Twelve tubes were tested for each of four concentrations. Inhibition was assessed using Limulus amoebocyte lysate reagent, depyrogenated vials, and pyrogen-free sterile micropipette tips. Each study was performed with four groups of solutions: decayed 18F-FDG, negative control, PPC and PWC. RESULTS: In the study of undiluted FDG, seven of 50 PPC vials at 12 EU x ml(-1) did not gel. The lowest endotoxin concentration that consistently gelled at 20 min was 4 EU x ml(-1) . In the sample tested for inhibition using PPC tubes at 4 EU x ml(-1) , 49 tubes gelled at 20 min, and one did not. CONCLUSION: The inhibition rate improved between undiluted (i.e., 7/50 (14%)) and diluted (i.e., 1/50 (2%)) FDG PPC trials (P=0.03). However, given that 1 of 50 trials failed for diluted FDG PPC, we conclude that inhibition still occurs and there is a 95% chance that the inhibition rate could be as high as 11% or as low as 0% on repetition of the experiment.

Artifacts↗
PubMed2002

The planning and design of a new PET radiochemistry facility.

The objectives of the Mayo positron emission tomography (PET) radiochemistry facility are the production of PET drugs for clinical service of our in-house patients, commercial distribution of PET drug products, and development of new PET drugs. The factors foremost in the planning and design phases were the current regulatory climate for PET drug production, radiation safety issues, and effective production flow. A medium-energy cyclotron was preferred for its small footprint to allow a compact vault, its high-proton energy to offer a higher product radioactivity; and its research capabilities. A vault installation was chosen instead of a self-shielded machine for improved access and ease of maintenance. Adjacent to the cyclotron is an area that houses the support equipment and a large dedicated workshop to support machine maintenance and targetry development. The total floor area of the PET radiochemistry facility is 344.2 m(2) (3,705.5 ft(2)), of which the radiochemistry laboratory occupies 130.7 m(2) (1,407 ft(2)). To reduce environmental contamination of PET drug products, the laboratory contains a controlled-air environment class 10,000 (M5.5) clean room with access via an interlocking entry change area. A fully shielded isolator (class 100 [M3.5]) is located in the clean room. The PET drugs are delivered via shielded tubing between the synthesizer and isolator. Inside the isolator, there is an automated device for dispensing the PET drug into either a bulk-activity vial or a unit-dose syringe. The dispensed PET radiopharmaceutical then passes through a hatch to a dedicated area where it is packaged for in-house use or commercial distribution. Unit doses for in-house patients are transported via pneumatic tube to the PET imaging area 76.2 m (250 ft) away. There is extensive radiation area monitoring throughout the facility that continuously measures radiation levels. We believe that our new PET radiochemistry facility not only meets overall objectives, but also provides an ergonomic, efficient working environment for the production and development of PET drugs.

Journal Article↗
PubMed2002

Effects of methylene blue stabilizer on in vitro viability and chemotaxis of 99mTc-exametazime-labeled leukocytes.

UNLABELLED: This study was conducted to evaluate the effects of methylene blue/phosphate buffer stabilizer on the labeling efficiency, cell membrane integrity, chemotaxis, and in vitro stability of leukocytes labeled with 99mTc-exametazime. METHODS: Whole blood (480 mL) was obtained from each of 3 healthy donors and divided equally into eight 60-mL aliquots. Two aliquots from each of the 3 subjects were used as a control (i.e., leukocytes were not labeled with either nonstabilized or stabilized 99mTc-exametazime) in this study. The remaining 6 aliquots from each of the 3 subjects were divided equally into the following formulation groups: (a) leukocytes labeled with nonstabilized 99mTc-exametazime, (b) leukocytes labeled with stabilized 99mTc-exametazime containing 250 microg methylene blue, and (c) leukocytes labeled with stabilized 99mTc-exametazime containing 500 microg methylene blue. Duplicate samples were evaluated to confirm the repeatability of the study. Six samples were studied under each experimental condition (i.e., control, a, b, and c groups). The cell membrane integrity and chemotatic capacity of leukocytes were measured at 1 and 3 h after preparation, whereas a complete blood count was obtained at 3 h after preparation. The labeling efficiency was calculated immediately on conclusion of cell labeling, whereas the in vitro stability of the radiolabeled leukocytes was evaluated at 3 h after radiolabeling. RESULTS: None of the samples showed trypan blue-stained cells. For the chemotactic index, no statistically significant differences were noted between the 3 labeling formulations at 1 h (P = 0.43) or 3 h (P = 0.10) after preparation. None of the labeling formulations differed significantly from the control values of the chemotactic index (all P > 0.25). For the complete blood count, no significant differences were observed between any of the groups, with the exception of platelet number in the control group (P = 0.004). The labeling efficiency (P = 0.10) and in vitro stability (P = 0.33) were also similar in our comparison of the 3 labeling formulations. CONCLUSION: With no major statistically significant difference noted either between the 3 labeling formulations or between the control and the 3 labeling formulations, we concluded that the methylene blue/phosphate buffer stabilizer (250 or 500 microg methylene blue) did not affect the cell membrane integrity, chemotactic capacity, labeling efficiency, in vitro stability, or complete blood count of leukocytes labeled with stabilized 99mTc-exametazime.

Cell Membrane↗
PubMed2002

Comparison of various requirements of the quality assurance procedures for (18)F-FDG injection.

The quality assurance (QA) requirements (i.e., test procedure, acceptance criteria, and testing schedule) for fludeoxyglucose (18)F ((18)F-FDG) injection listed in the U.S. Pharmacopeia (USP); the draft Chemistry, Manufacturing, and Controls (CMC) issued by the U.S. Food and Drug Administration (FDA); and the European Pharmacopeia (EP) were compared. The FDA Modernization Act of 1997 requires that the QA of compounded PET drug products be in compliance with the PET compounding standards and official monographs included in the USP. However, the "sunset" clause of the PET section within the FDA Modernization Act of 1997 stipulates that all PET drug products, in due course, must meet the requirements for drug approval procedures and current good manufacturing practice, and the FDA has issued a draft CMC that includes QA specifications for (18)F-FDG injection. The purpose of this article is to discuss the pros and cons of each of the QA tests stated in the USP, CMC, and EP and to propose a practical testing method for each required test, thereby helping end users to ensure the quality of the (18)F-FDG injection product. It is hoped that this article will stimulate further cooperation among various countries worldwide in the development of a set of harmonized and sensible QA standards for all PET drug products.

Drug Compounding↗
PubMedDate not supplied

A rational regulatory approach for positron emission tomography imaging probes: from "first in man" to NDA approval and reimbursement.

We propose a new regulatory approach for positron emission tomography (PET) molecular imaging probes, essential tools in today's medicine. Even though the focus of this paper is on positron-emitting labeled probes, it is also justified to extend this proposed regulatory approach to other diagnostic nuclear medicine radiopharmaceuticals. Key aspects of this proposal include: (1) PET molecular imaging probes would be placed in a "no significant risk" category, similar to that category for devices in current Food and Drug Administration (FDA) regulations, based on overwhelming scientific evidence that demonstrates their faultless safety profile; (2) the FDA-sanctioned Radioactive Drug Research Committee (RDRC) will oversee all diagnostic research with these probes. The newly defined RDRC should approve "first in man" use; supervise a broader spectrum of diagnostic research protocols, including those looking to demonstrate initial efficacy, as well as multicenter clinical trials and the use of molecular imaging probes as a screening tool in drug discovery. The current investigational new drug (IND) mechanism is thus eliminated for these diagnostic probes; (3) when a molecular imaging probe has demonstrated diagnostic efficacy, FDA approval (i.e., NDA) will be sought. The review will be done by a newly constituted Radioactive Drug Advisory Committee (RDAC) composed of experts chosen by the professional societies, who would provide a binding assessment of the adequacy of the safety and efficacy data. When the RDAC recommends its diagnostic use on scientific and medical grounds, the molecular imaging probe becomes FDA approved. After a molecular imaging probe is approved for a diagnostic indication, the existing mechanism to seek reimbursement will be utilized; and (4) the FDA would retain its direct oversight function for traditional manufacturers engaged in commercial distribution of the approved diagnostic molecular imaging probes (i.e., under NDA) to monitor compliance with existing US Pharmacopeia (USP) requirements. With abbreviated and more appropriate regulations, new PET molecular imaging probes for diagnostic use would be then rapidly incorporated into the mainstream diagnostic medicine. Equally importantly, this approach would facilitate the use of molecular imaging in drug discovery and development, which would substantially reduce the costs and time required to bring new therapeutic drugs to market.

Animals↗
PubMedDate not supplied

In-house preparation of technetium 99m-labeled human serum albumin for evaluation of protein-losing gastroenteropathy.

OBJECTIVE: To develop an in-house preparation method for technetium 99m-labeled human serum albumin (99mTc-HSA) to meet the clinical need for gastrointestinal (GI) protein loss evaluation in our institution. DESIGN/SETTING: Our in-house HSA was prepared by slowly adding 2 mL of 25% HSA to 50 mL nitrogen-purged, sterilized water. We then continued the nitrogen purging process for another 15 minutes before adding 0.5 mL of stannous chloride (SnCl2) in concentrated hydrochloride (40 mg/mL) to the HSA solution. Next, we transferred 1 mL of the mixture to a 5 mL vial containing 0.5 mL of 30 mCi (1,110 MBq) 99mTc. Using a paper chromatography method during a 6-hour postpreparation time period, we evaluated the effects of filtration (0.2 microm membrane filter versus no filtration) and storage temperature (25 degrees C versus 37 degrees C) on the in vitro stability of 99mTc-HSA. PATIENTS OR OTHER PARTICIPANTS: In this study, we employed the in-house 99mTc-HSA preparation to study GI protein loss in two patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We used a radiochemical purity (RCP) value of not less than 90% as the index for determining in vitro stability of the in-house 99mTc-HSA preparation. The nuclear medicine physician interpreted the image to determine the location and extent of protein loss in the GI tract. RESULTS: Our results demonstrate that the overall RCP of 99mTc-HSA was 95.0% +/- 2.2% (mean +/- SD). We found no statistically significant difference in RCP value between filtered and nonfiltered 99mTc-HSA preparations across the sampled time points. However, RCP values tended to increase with time for each of the temperature-controlled preparations (P < .01). Storage temperature had a significant effect (P < .01), with refrigerated samples having an estimated 2.2% lower RCP value across time. However, the difference between room temperature and refrigerated samples decreased over time (P < .02) to only 1.1% at the 6-hour sampling. We noted gradual accumulation of 99mTc-HSA within the first hour in one patient, and the imaging results indicate that both patients had protein-losing enteropathy. CONCLUSION: It is relatively easy to prepare 99mTc-HSA in-house, achieving a high RCP level as well as extended in vitro stability. The clinical data further indicate that our in-house preparation of 99mTc-HSA may be useful for the study of GI protein loss; however, further clinical evaluation is needed.

Analysis of Variance↗
PubMedDate not supplied

Explanations and unresolved issues pertaining to the development of the Nuclear Pharmacy Compounding Guidelines.

OBJECTIVES: To provide background information related to the development of the Nuclear Pharmacy Compounding Guidelines, to discuss regulatory complexities related to radiopharmaceutical compounding practice, and to summarize the gaps in the current compounding regulations for radiopharmaceuticals. DATA SOURCES: The Guidelines closely follow the provisions of section 503A of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the monographs and chapters related to pharmacy compounding in the United States Pharmacopeia (USP), and the recommended guidelines published by the American Society of Health-System Pharmacists. SUMMARY: The Food and Drug Administration Modernization Act (FDAMA) of 1997 established parameters under which the compounding of drug products is appropriate and lawful, but these criteria expressly do not apply to radiopharmaceuticals. The Nuclear Pharmacy Compounding Practice Committee, a group of nuclear pharmacists convened by the American Pharmaceutical Association, developed the Nuclear Pharmacy Compounding Guidelines to establish a set of principles and guidelines for good radiopharmaceutical compounding practice. The intent of the new document is to provide guidance on radiopharmaceutical compounding practices that have evolved over the last 2 decades and to place them in an appropriate regulatory framework in accordance with previous enforcement policies and guidelines issued by the U.S. Food and Drug Administration (FDA) regarding the exemption of certain pharmacy practices from enforcement of adulteration, misbranding, and new drug requirements. CONCLUSION: The Nuclear Pharmacy Compounding Guidelines, recently released by APhA, is the first official document that provides realistic and practical compounding guidance for nuclear pharmacists. Even though the United States Court of Appeals for the Ninth Circuit recently ruled section 503A of the FD&C Act to be invalid in its entirety, and the Supreme Court upheld that ruling, the compliance policy guides issued by FDA in March 1992 and revised in May 2002 maintain guiding principles on pharmacy compounding similar to those stated in section 503A of the FD&C Act. The Nuclear Pharmacy Compounding Practice Committee is optimistic that the practical information contained in the Guidelines will assist state boards of pharmacy, FDA, and the United States Pharmacopeial Convention in setting appropriate standards for nuclear pharmacy compounding practice that will ensure the continued availability of high-quality compounded radiopharmaceuticals at reasonable cost.

Drug Compounding↗
PubMedDate not supplied

Deficiencies of product labeling directions for the preparation of radiopharmaceuticals.

OBJECTIVE: To identify potential deficiencies in product labeling (package insert) instructions for the preparation of radiopharmaceuticals. METHODS: Preparation instructions, which include both reconstitution and quality control (QC) directions, as stated in the package inserts were evaluated for all commercially available reconstituted radiopharmaceuticals. Reviews of the package inserts were initially performed by each author, and then all identified deficiencies were compiled and evaluated by all authors. The preparation scenario for each package insert evaluated was based on a centralized nuclear pharmacy operation assuming typical support personnel, standard operating equipment, and workload. MAIN OUTCOME MEASURE: The instructions as stated in each package insert for the preparation (including QC) were rated as inadequate if a satisfactory preparation could not be prepared by a nuclear pharmacist or physician when instructions were followed exactly. RESULTS: Identified deficiencies in package insert instructions for the preparation of radiopharmaceuticals fell into the following five categories: (1) absent or incomplete directions (especially with regard to QC procedures); (2) restrictive directions (e.g., specific requirement to use designated needles, chromatography solvents, counting devices), (3) inconsistent directions (e.g., different reconstituted volumes for the same final drug product, unworkable expiration times); (4) impractical directions (e.g., unrealistically low reconstituted activity limits, dangerously high number of radiolabeled particles); and (5) vague directions (e.g., use of the words "should," "may," "recommend"). CONCLUSION: Manufacturers' directions for the preparation of radiopharmaceuticals often contain deficiencies and should be viewed as standard guidance rather than as requirements. Just as physicians are permitted to use U.S. Food and Drug Administration (FDA)-approved drugs for off-label indications, nuclear pharmacists should be allowed to use alternative methods for preparing radiopharmaceuticals, provided those methods have been validated to be as good as the stated directions and that the nuclear pharmacists do not engage in activities that fall outside the normal practice of pharmacy. Manufacturers, FDA, nuclear pharmacists, and nuclear physicians should work together to address identified deficiencies in package insert directions.

Drug Compounding↗
PubMedDate not supplied

In-process 20-minute endotoxin "limit test" for positron emission tomography radiopharmaceuticals.

OBJECTIVES: To discuss various issues related to the in-process 20-minute endotoxin "limit test" (20-minute bacterial endotoxin test [BET]) per the United Stated Pharmacopeia (USP) general chapter <823>, "Radiopharmaceuticals for Positron Emission Tomography--Compounding". DATA SOURCES: The online version of 2005 USP, and other relevant articles from the published biomedical literature. SUMMARY: The minimum endotoxin level to be used for the positive controls, minimum allowable volume for administration, procedure and interpretation of the above test, and whether the 20-minute BET is required and suitable for use with any positron emission tomography (PET) radiopharmaceutical labeled with a radionuclide having a physical half-life less than 20 minutes are discussed in this article. Neither the current USP nor other publications related to the performance of the 20-minute BET provide complete detailed information or explanation with regard to the issues discussed. CONCLUSION: To allow end users to accurately and, more importantly, faithfully execute the above testing, specific information needs to be made readily available concerning the 20-minute BET.

Drug Contamination↗