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J C Hung

Publications and source records attributed to J C Hung.

At least 19 recordsLinked to original sources

Effects of alternative reconstitution procedures on the labelling efficiency and in vitro stability of 99Tcm-labelled radiopharmaceuticals.

Adding normal saline (NS) separately before 99Tcm-sodium pertechnetate to MDP cold kits has been shown to reduce substantially the radiation dose to the hand. A similar dose reduction will probably prove to be valid with the preparation of most other 99Tcm-labelled radiopharmaceuticals. However, it is unknown how this altered reconstitution procedure may affect the labelling efficiency and in vitro stability of the 99Tcm-labelled radiopharmaceuticals. We have evaluated the effects on the labelling efficiency and in vitro stability of 99Tcm-labelled MDP, mertiatide and sestamibi reconstituted with three different methods: adding normal saline before 99Tcm activity (NS/Tc); adding 99Tcm activity before normal saline (Tc/NS); and the standard reconstitution method of adding both 99Tcm activity and normal saline together. The labelling efficiency and in vitro stability were evaluated by measuring the radiochemical purity of each radiopharmaceutical tested at 0, 1, 3, 6, 12 (except 99Tcm-MDP) and 24 h after reconstitution. For 99Tc-mertiatide, there was a very slight difference in the labelling efficiency, mostly due to the Tc/NS method being approximately 0.29% lower across time post-reconstitution than the standard method. For 99Tcm-labelled MDP and sestamibi, there were no differences between the three methods in terms of labelling efficiency and in vitro stability. In conclusion, both alternative methods (i.e. NS/Tc and Tc/NS) appear not to have any detrimental effect on the labelling efficiency and in vitro stability of the 99Tcm-labelled radiopharmaceuticals that we tested. However, of the two alternative kit reconstitution methods, we recommend the NS/Tc method, since it may reduce the hand radiation dose.

Drug Stability

Pulmonary function monitoring during adenosine myocardial perfusion scintigraphy in patients with chronic obstructive pulmonary disease.

OBJECTIVE: To determine whether adenosine could be safely administered to patients with chronic obstructive pulmonary disease (COPD) for coronary vasodilatation during perfusion scintigraphy without causing bronchospasm. MATERIAL AND METHODS: The study was divided into two phases. In the monitoring phase, patients with COPD were pretreated with an inhaled bronchodilator (albuterol) and had pulmonary function monitored during the infusion of a graduated dose of adenosine. Eligibility for entry into this phase of the study was determined on the basis of results of pulmonary function testing (PFT) during resting. Once we had shown that adenosine could be safely administered to patients with COPD, an implementation phase was begun. Entry did not require resting PFT, and patients were administered adenosine without monitoring of pulmonary function. Differences between patients with normal pulmonary function or mild COPD and those with more severe COPD were analyzed statistically. RESULTS: Of 94 patients entered into the monitoring phase, none had obvious bronchospasm. The dosage of adenosine was reduced in four patients because of a decrease in forced expiratory volume in 1 second (FEV1) of 20% in comparison with baseline (FEV1 before administration of albuterol). The mean FEV1 decreased slightly from 1.83 L after administration of albuterol to 1.78 L during the maximal adenosine dose. Patients with a remote history of asthma, positive result of a methacholine challenge test, or mild COPD (FEV1 60 to 80% of the maximal predicted value for age) did not differ significantly in their response to infusion of adenosine from those with moderate or severe COPD (FEV1 30 to 59% of the maximum predicted for age). Of 117 patients in the implementation phase, 2 had bronchospasm during infusion of adenosine that was quickly terminated by stopping the administration in one patient and reducing the dose of adenosine in the other. CONCLUSION: This study shows that adenosine can be safely administered intravenously to selected patients with known or suspected COPD to produce coronary vasodilatation for myocardial perfusion imaging. Patients who are within the guidelines established for this study should be considered for adenosine coronary vasodilatation with use of bronchodilator pretreatment, a graduated dose of adenosine, and regular chest auscultation during the infusion.

Adenosine

The use of human glutathione S-transferase A1 in the detection of cystic fibrosis liver disease.

OBJECTIVE: To determine the value of serum human glutathione S-transferase A1 (hGST A1) in the detection of cystic fibrosis liver disease (CFLD). METHODS: Sixty-three children (aged 0.5-16 years) with cystic fibrosis (CF) were screened prospectively for evidence of hepatobiliary abnormalities between February 1993 and February 1996. Comparison was made between clinical examination, abdominal ultrasonic scan, measurement of conventional liver enzymes (LFTs) and serum hGST A1 concentration in the detection of hepatobiliary abnormalities in children with CF. RESULTS: The 5-95% concentration of serum hGST A1 was 1.7-4.27 micrograms L-1 for the control group. The hGST A1 levels in the CF patients were significantly higher than in the non-CF group. Thirty-eight (60%) children had detectable hepatobiliary abnormalities. Ultrasound scanning detected the highest number of abnormalities (41%), followed by hGST A1 (30%). The presence of clinical liver disease was found in 19% of the children. The estimated sensitivities of detecting CFLD by clinical method, ultrasound scan, serum hGST A1, and LFTs would be 32%, 68%, 50% and 16%, respectively. CONCLUSIONS: Serum hGST A1 measurement increases the sensitivity of detecting hepatic abnormalities when included with clinical and ultrasound evaluation although, in some cases with advanced liver disease, serum hGST A1 may be normal. Conventional liver enzyme tests add little information in the detection of CF liver disease.

Adolescent

Activated charcoal as a potential radioactive marker for gastrointestinal studies.

The scintigraphic measurement of colonic transit is currently performed using 111In ion exchange resin pellets delivered to the colon in a capsule coated with a pH sensitive polymer, methacrylate, which dissolves in the distal ileum. However, in the USA, this requires an investigational drug permit. Our aim was to evaluate the in vitro binding characteristics of activated charcoal in milieus that mimicked gastric and small intestinal content. The in vitro incubation of activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In-DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We estimated the association of radiopharmaceuticals with the activated charcoal over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the association of activated charcoal with the other radiopharmaceuticals was approximately 100% throughout the 3 h incubation. In conclusion, activated charcoal appears to adsorb avidly with common radioisotopes, and appears promising as an alternative to resin ion exchange pellets used for the measurement of gastrointestinal transit by scintigraphy.

Charcoal

Radiolabelled mixed leukocytes and pure granulocytes with stabilized 99Tcm-exametazime.

Although the methylene blue stabilizer extends the shelf life of 99Tcm-exametazime to 4-6 h after reconstitution, the dark blue appearance of the mixture of stabilized 99Tcm-exametazime and blood components makes it impossible to separate out the leukocyte button. The aim of this study was to assess the feasibility of using stabilized 99Tcm-exametazime to radiolabel mixed leukocytes separated by Volex sedimentation with hypotonic lysis (VL) and pure granulocytes isolated by a single-density Ficoll-Hypaque gradient with hypotonic lysis (FL). Isolated cells from 40-ml and 80-ml donor blood samples were mixed with 0.5 ml stabilized 99Tcm-exametazime (approximately 925 MBq 99Tcm and 62.5 micrograms exametazime) and incubated at room temperature for 15 min. After incubation, two dilution steps with 3 ml and 9 ml of 12.6% ACD/NS (anticoagulant citrate dextrose, solution A, USP, mixed with 0.9% NaCl, v/v) were conducted to dilute the dark blue mixture and to remove any unbound 99Tcm activity. With the addition of 9 ml of 12.6% ACD/NS solution to the 1-ml bottom portion from the first dilution, the supernatant of the centrifuged preparation was clear enough to be withdrawn. The overall labelling efficiency (LE) of labelled leukocytes and granulocytes was 87.1 +/- 4.9% and 87.7 +/- 6.2%, respectively (n = 12 each). Overall, radiolabelled cells (n = 12) from the 80-ml blood samples (LE = 90.3 +/- 2.8%) had an approximately 6% higher labelling efficiency than from the 40-ml blood samples (LE = 84.5 +/- 6.0%) and also had a slightly better in vitro stability compared to the 40-ml samples. The in vitro stability studies showed that only approximately 2% (n = 48) 99Tcm activity was eluted each hour from the radiolabelled leukocytes or granulocytes for the 40-ml or 80-ml blood samples during the 6-h evaluation period. Cell viability of all labelled leukocyte samples was confirmed by the trypan blue staining technique. In conclusion, mixed leukocytes separated by the VL method and pure granulocytes isolated by the FL method can be effectively labelled with stabilized 99Tcm-exametazime with the use of the 'double dilution' technique.

Cell Survival

Use of stabilized technetium-99m-exametazime for radiolabeling leukocytes.

UNLABELLED: With a stabilizing agent (i.e., methylene blue and sodium phosphate buffer mixture), the in vitro stability of 99mTc-exametazime has been increased to 4-6 hr postreconstitution. However, it is not feasible to use the stabilized 99mTc-exametazime for leukocyte radiolabeling. This is due to the deep blue appearance of the mixture of stabilized 99mTc-exametazime and blood components, which makes it impossible to separate properly the supernatant from the leukocyte button. In our study, we have developed a practical methodology for overcoming this difficulty in order to use stabilized 99mTc-exametazime in leukocyte labeling. METHODS: The stabilized 99mTc-exametazime preparation used in our method consisted of 2 ml 7.4-8.0 GBq (200-215 mCi) 99mTc and 2 ml methylene blue/phosphate buffer solution. The separated leukocytes from 80-ml fresh venous blood were incubated with three different ages (i.e., 0-, 4-, or 6-hr postreconstitution) of stabilized 99mTc-exametazime (approximately 925 MBq, approximately 25 mCi; 0.5-1 ml) at room temperature for 15 min. After incubation, 3 ml of 12.6% ACD/NS solution (anticoagulant citrate dextrose, solution A, USP mixed with 0.9% NaCl, v/v) was added to the tube and centrifuged at 160 g for 5 min. Three milliliters of the dark blue supernatant were carefully removed, and the bottom 1 ml portion was resuspended with 9 ml of 12.6% ACD/NS solution. After centrifugation (160 g for 5 min), the supernatant was clear enough to be drawn off without disturbing the radiolabeled leukocyte button. The white cell button was then resuspended in 4 ml of platelet-poor plasma. RESULTS: The overall labeling efficiency (LE) of our new technique was 67.8%-91.9%, with the higher LE associated with fresher stabilized 99mTc-exametazime. During a 6-hr in vitro stability evaluation, radiolabeled leukocytes lost 1.2% +/- 0.3% (n = 24), 1.3% +/- 0.1% (n = 16) and 1.8% +/- 0.1% (n = 16) each hour of the cell-bound 0-, 4-, and 6-hr-old 99mTc-exametazime, respectively. The 99mTc-exametazime-labeled leukocytes examined by the trypan blue staining technique at 6-hr postradiolabeling yielded nonstained cells indicating viable leukocytes. CONCLUSION: We concluded that with a small volume of 99mTc-exametazime and double dilution steps with 12.6% ACD/NS solution, stabilized 99mTc-exametazime can be used effectively for leukocyte radiolabeling with a high LE and long in vitro stability.

Drug Stability

Rapid preparation method for technetium-99m bicisate.

The method currently recommended for the preparation of technetium-99m bicisate (99mTc-bicisate) requires a lengthy 30-min incubation at room temperature. The purpose of this study was to evaluate an alternative method to shorten the preparation time. 99mTc-bicisate was prepared with 3.7 GBq (100 mCi) 99mTc according to the manufacturer's instructions, except for the final incubation step, which was replaced with the microwave heating procedure. A standard thin-layer chromatography (TLC) method (i.e., Baker-Flex silica gel IB-F TLC plate with ethyl acetate as mobile phase) was used for the determination of the radiochemical purity (RCP) of 99mTc-bicisate. Our evaluation with different microwave heating processes (300 W with different heating times) demonstrated that as the microwave heating temperature was increased (i.e., 44 masculine-71 masculine C), an increased percentage of samples reached 95% within 5 min post preparation (n=58). The highest RCP value (i.e., 97.4%+/-0.5%, n=10) could be obtained immediately after an 8-s microwave heating time at 300 W (microwave temperature at 69 masculine C), and an average RCP value of 96.4%+/-1.3% (n=90) was maintained throughout the 24-h evaluation period. However, the trend seemed to reverse at higher microwave temperatures (i.e., 76 masculine-90 masculine C), which reconfirmed our initial findings that overheating had no benefit for the preparation of 99mTc-bicisate. To ensure that temperature was the only determining factor, a hot water incubator set at 69 masculine C was used (n=6). Similar RCP results were achieved. In conclusion, the use of a microwave oven at a low heat cycle provides a rapid and efficient way to prepare 99mTc-bicisate.

Chromatography, Thin Layer

Faster and easier radiochemical purity testing for [125I]sodium iothalamate.

A previous method for determination of the radiochemical purity (RCP) value of [125I]sodium iothalamate uses two paper strips and solvents (total developing time is approximately 2.5 h). To simplify and shorten the RCP testing procedure, our laboratory has developed a single-strip chromatography method that not only distributes free 125I and [125I]sodium iothalamate to different relative front (Rf) locations, but is also faster and easier to perform. RCP of [125I]sodium iothalamate was determined with the use of a 10-cm instant thin-layer chromatography strip impregnated with polysilicic acid gel (ITLC-SA) as the solid phase, and a mobile phase of 2-butanol:acetic acid:water (140:2.5:70, v/v). By using autoradiography and counting the strip segments in a gamma counter, our results indicated that free 125I migrated to Rf = 0.89-1.00 while the [125I]sodium iothalamate moved to Rf = 0.44-0.67. The total developing time for the single-strip ITLC-SA system was approximately 1 h.

Autoradiography

Radioiodine dispensing and usage in a centralized hospital nuclear pharmacy.

131I sodium iodide is the radiopharmaceutical of choice for both diagnosis and therapy in patients with various thyroid abnormalities. The radioiodide capsule has been the preferred dosage form, primarily because it provides a more convenient and safer vehicle for radioiodine administration. However, encapsulated 131I costs approximately twice as much a liquid 131I and does not provide as much flexibility as 131I solution in dosage selection. Also, the bioavailability of the capsular radioiodide preparation is inferior to that of the aqueous dosage form. The patient must swallow multiple capsules when a large amount of 131I activity is used. Capsule form is not suitable for any patient who has difficulty swallowing a capsule, has a feeding tube, or requires intravenous injection of 131I solution. In addition, radioiodide capsules must be analyzed statistically to ensure that the dosage units meet the United States Pharmacopeia uniformity requirements. If liquid radioiodine is used, distilled water rather than tap water should be used for dose preparation. It also is recommended that an antioxidant (e.g., sodium thiosulfate, sodium bisulfite), disodium edetate, and a pH adjustment of 7.5-9.0 be used to reduce radioiodide volatility. Due to the acceleration of the oxidative reaction caused by heat and light, 131I should be stored in a dark, cool environment. To comply with the quality management program implemented by the US Nuclear Regulatory Commission on January 27, 1992, all of the required information (e.g., prescribed dosage, procedure date, and signature of the authorized user) for a valid written directive is preprinted to ensure that the written directive is completed entirely and appropriately. Before each administration of therapeutic 131I solution, the calculated dose is verified by the prescribing physician, and the measured dose of 131I is reconfirmed by a second nuclear medicine technologist. Each patient's identity is verified by two methods (i.e., patient's full name and birth date).

Biological Availability

Myositis ossificans complicating severe Guillain-Barré syndrome.

We report myositis ossificans occurring in a 13-year-old boy with severe and rapidly progressive Guillain-Barré syndrome. This complication should be considered when severe musculoskeletal pain is experienced by such patients. Disodium etidronate may be of benefit in this condition.

Adolescent

Colonic transit scintigraphy labeled activated charcoal compared with ion exchange pellets.

UNLABELLED: Scintigraphic measurement of colonic transit is currently performed by delivering 111In ion exchange resin pellets to the colon in a methacrylate-coated capsule. However, use of this method is constrained by the need for an investigational drug permit. We have demonstrated previously optimal adsorption in vitro of commonly used radioisotopes (e.g., 99mTc or 111In) to activated charcoal in milieus that mimicked gastric and small intestinal content. The aim of this study was to compare the transit profiles of radioactive activated charcoal and resin pellets delivered to the colon in the same methacrylate-coated capsule. METHODS: In 10 healthy volunteers, we compared the colonic transit profiles over 32 hr of simultaneously administered resin pellets labeled with 111In and activated charcoal mixed with 99mTc-diethylenetriaminepentaacetic acid. Transit was summarized as the geometric center (weighted average of counts) in the colon at each scanning period. RESULTS: Colonic transit profiles were virtually identical with the two markers, with less than 0.1 geometric center unit differences in the transit profiles over the 32-hr periods. CONCLUSION: Activated charcoal is a suitable alternative to resin pellets when delivered in a methacrylate-coated, delayed-release capsule to the colon for measurement of transit by scintigraphy.

Adult

Optimal conditions of 99mTc eluate for the radiolabeling of 99mTc-sestamibi.

Our nuclear pharmacy has reported that a failed radiochemical purity (RCP) (i.e., RCP < 90%) of 99mTc-sestamibi may be associated with the use of a first elution at later stages from a long-ingrowth time (i.e., > or = 72 h) wet-column generator. The primary purpose of this study was to evaluate the effects of 99mTc eluates from wet- and dry-column generators on the RCP of 99mTc-sestamibi under the above conditions. RCP values were found to be measurably higher and kit failure rates lower with the use of dry-column generator eluate. Using a dry-column generator eluate, Cardiolite kits were prepared with 11.10 GBq of 99mTc at 3, 4, and 5 h postelution and 5.55 GBq at 6, 10, 11, and 12 h postelution. Our data suggest that when 11.10 GBq of 99mTc from a dry-column generator with > or = 72-h ingrowth was used to prepare 99mTc-sestamibi, kit failure started to occur using 99mTc eluate at approximately 4 h postelution. When 5.55 GBq was used to reconstitute the kit, RCP failure began to occur using 99mTc eluate approximately 10 h postelution and wet-column generators; the failure rate can be reduced even further by avoiding the addition of high activities of 99mTc and long elution times.

Indicators and Reagents

Radiopharmaceutical-related pitfalls and artifacts.

The primary goal of this review article is to increase the reader's knowledge and understanding of problems associated with the radiopharmaceuticals commonly used in daily practice. To achieve this objective, problems related to the commonly used radiopharmaceuticals are divided into pitfalls and artifacts related to radiopharmaceutical preparation (technetium-99m [99mTc]-labeled and non-99mTc-labeled radiopharmaceutical) and those related to radiopharmaceutical administration. For the radiopharmaceutical formulation-associated pitfalls and artifacts, problems are discussed in terms of factor categories, such as factors associated with radionuclides, factors associated with components, factors associated with preparation procedures, and miscellaneous factors. As for the pitfalls and artifacts caused by radiopharmaceutical administration, these problems are categorized into errors associated with administration technique and nontechnical errors. Clinical manifestations (ie, appearance upon imaging) from the numerous literature-based examples are presented. The effect of the causative factors and the reason each factor can result in radiopharmaceutical preparation and administration problems are discussed. In addition, the possible preventive actions are presented for each group. However, the cause of some pharmaceutical related problems may not be easily recognized, and thus it is difficult to develop preventive and/or corrective plans for these cases.

Artifacts

A comparison of current regulations and regulatory guide governing quality control of dose calibrators.

The U.S. Nuclear Regulatory Commission recently amended its regulation governing the calibration of dose calibrators. The changes include (1) the radioactivity of radiopharmaceutical dosages that contain photon-emitting radionuclides has to be measured by a dose calibrator prior to administration to patients and human research subjects; (2) the lower end of the radioactivity limits for linearity testing has been raised to 1.1 MBq (30 microCi) to be consistent with the Nuclear Regulatory Commission Quality Management Program Requirements; and (3) the requirement for signature of the Radiation Safety Officer on the records for accuracy, linearity, and geometry dependence tests has been removed. Although these are practical amendments, further clarification of the new Nuclear Regulatory Commission regulation is required for the following issues: (1) inconsistency in individual's identification requirement for the record keeping (i.e., initials of the individual who performed the constancy check and identity of the operator for the accuracy, linearity, and geometry dependence tests); (2) whether the use of 99mTc is adequate for linearity testing when other radionuclides are being measured in the dose calibrator; and (3) lack of provision for dose calibrator adjustment when conducting the accuracy test. In addition, Nuclear Regulatory Commission Regulatory Guide 10.8 should be revised to become consistent with the Nuclear Regulatory Commission's regulation in order to assist licensees with full compliance of the requirements or recommendations.

Government Agencies