Outpatient treatment with (131)I-anti-B1 antibody: radiation exposure to family members.

UNLABELLED: The Nuclear Regulatory Commission (NRC) regulations that govern release of patients administered radioactive material have been revised to include dose-based criteria in addition to the conventional activity-based criteria. A licensee may now release a patient if the total effective dose equivalent to another individual from exposure to the released patient is not likely to exceed 5 mSv (500 mrem). The result of this dose-based release limit is that now many patients given therapeutic amounts of radioactive material no longer require hospitalization. This article presents measured dose data for 26 family members exposed to 22 patients treated for non-Hodgkin's lymphoma with (131)I-anti-B1 antibody after their release according to the new NRC dose-based regulations. METHODS: The patients received administered activities ranging from 0.94 to 4.77 GBq (25--129 mCi). Family members were provided with radiation monitoring devices (film badges, thermoluminescent or optically stimulated luminescent dosimeters, or electronic digital dosimeters). Radiation safety personnel instructed the family members on the proper wearing and use of the devices. Instruction was also provided on actions recommended to maintain doses to potentially exposed individuals as low as is reasonably achievable. RESULTS: Family members wore the dosimeters for 2--17 d, with the range of measured dose values extending from 0.17 to 4.09 mSv (17--409 mrem). The average dose for infinite time based on dosimeter readings was 32% of the predicted doses projected to be received by the family members using the NRC method provided in regulatory guide 8.39. CONCLUSION: Therapy with (131)I-anti-B1 antibody can be conducted on an outpatient basis using the established recommended protocol. The patients can be released immediately with confidence that doses to other individuals will be below the 5-mSv (500 mrem) limit.

Feasibility and safety of outpatient Bexxar therapy (tositumomab and iodine I 131 tositumomab) for non-Hodgkin's lymphoma based on radiation doses to family members.

Radioimmunotherapy with anti-CD20 antibodies is a promising treatment approach for relapsed low-grade non-Hodgkin's lymphoma. Under revised Nuclear Regulatory Commission regulations (May 1997), patients may be released following treatment provided the maximum dose to any individual is not likely to exceed 500 mrem. Non-Hodgkin's lymphoma patients have been studied to evaluate radiation exposure to caregivers/family members after outpatient treatment with tositumomab and iodine I 131 tositumomab (Bexxar therapy). Estimates of total radiation doses to individuals expected to be maximally exposed to patients posttreatment have revealed that the doses should be within revised guidelines. In a University of Nebraska Medical Center study, the predicted total radiation doses (based on patient dose rate at 1 meter) ranged from 95-423 mrem. Family members were provided radiation-monitoring devices to directly monitor radiation exposure. Measured doses ranged from 10-409 mrem. In this and other studies, estimated and measured dose equivalents to maximally exposed individuals were below 500 mrem. Measured doses were, in most instances, lower than those predicted by patient-specific calculations, thus confirming the validity of the calculated dose predictions. Therefore, radioimmunotherapy with tositumomab and iodine I 131 tositumomab can be safely conducted on an outpatient basis.

Patient-specific dosimetry of indium-111- and yttrium-90-labeled monoclonal antibody CC49.

UNLABELLED: The objective of this work was to develop patient-specific dosimetry for patients with metastatic gastrointestinal tract cancers who received 111In-CC49 IgG for imaging before therapy with 90Y-CC49 IgG. METHODS: Whole-body imaging of 12 patients, who received 111-185 MBq (3-5 mCi) of 111In-CC49, commenced in < 2 hr postinfusion and was continued daily for 4-5 days. SPECT data were acquired at 24 and 72 hr to determine the range of 111In-CC49 activity concentrations in tumors and normal organs. Time-activity curves were generated from the image data and scaled from 111In-CC49 to 90Y-CC49 for dosimetric purposes. Absorbed-dose calculations for 90Y-CC49 included the mean and range in tumor and normal organs. Computed 90Y-CC49 activity concentrations were compared with measurements on 10 needle biopsies of normal liver and four tumor biopsies. RESULTS: In 9 of 10 normal liver samples, the range of computed 90Y-CC49 activity concentrations bracketed measured values. This was also the case for 3 of 4 tumor biopsies. Absorbed-dose calculations for 90Y-CC49 were based on patients' images and activities in tissue samples and, hence, were patient-specific. CONCLUSION: For the radiolabeled antibody preparations used in this study, quantitative imaging of 111In-CC49 provided the data required for 90Y-CC49 dosimetry. The range of activities in patients' SPECT images was determined for a meaningful comparison of measured and computed values. Knowledge of activity distributions in tumors and normal organs was essential for computing mean values and ranges of absorbed dose and provided a more complete description of the absorbed dose from 90Y-CC49 than was possible with planar methods.

Radiolabeled iododeoxyuridine: safety evaluation.

UNLABELLED: The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration. METHODS: Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained. RESULTS: To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation. CONCLUSION: When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.

National survey of quality assurance activities for pharmacy-prepared sterile products in hospitals.

The results of a survey of pharmacy department activities for quality assurance in the preparation of sterile drug products in short-term, nonfederal hospitals are reported. A questionnaire was mailed in March and April 1991 to pharmacy directors at hospitals that had indicated in ASHP's 1990 national survey of pharmaceutical services that they had formal quality assurance processes for intravenous admixture preparation. The adjusted gross sample size was 465. The net response rate was 71% (330 usable replies). Nearly all respondents indicated that sterile drug products were prepared extemporaneously in their departments; 61% reported batch preparation of such products. Both pharmacists and pharmacy technicians prepared sterile products. Respondents identified which guidelines were used in developing departmental policies and procedures for sterile product preparation. Specific areas were identified in which educational programs for pharmacists are needed; the most frequently indicated area (85%) was principles of aseptic technique. A majority of respondents used the following means for the orientation and training of personnel who prepare sterile products: aseptic technique lectures or videotapes, on-the-job training, written policies and procedures, and direct observation of technique. Almost all of the respondents (99%) had laminar-airflow hoods in their departments. Three fourths of those respondents indicated that laminar-airflow hoods were located in a limited-access room. Half of the respondents reported that laminar-airflow hoods were located certified every six months and that prefilters were changed monthly. Less than one third sampled environmental areas for microbial contamination. Less than one third of the surveyed hospitals routinely sampled sterile products for microbial contamination or pyrogens. Almost half indicated the absence of policies and procedures for testing chemical purity, drug concentration, sterility, pyrogenicity, or the environment for sterile preparations. Few respondents indicated the use of sterilization techniques other than microbial filtration, which was used by 32% of pharmacies involved in extemporaneous preparation and 16% of those involved in batch preparation. About 90% of the respondents used published references and manufacturers' recommendations to determine expiration dating. This survey revealed that certain quality assurance procedures related to pharmacy-prepared sterile products need major improvement.

Radiolabeled 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine--I. Synthesis and purification.

The purpose of this investigation was to synthesize and purify radiolabeled 9- or 10-monoiodostearyl carnitine for potential use as a perfusion and metabolic imaging agent for the heart. Oleic acid was iodinated via a free radical addition reaction of HI across the double bond to give 9- or 10-monoiodostearic acid which in turn was esterified with carnitine. The identity of 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine was determined using nuclear magnetic resonance (NMR), infrared (i.r.), ultraviolet (u.v.), and mass spectroscopy. The purity of the fatty acid and carnitine ester was established by thin layer chromatography. 9- or 10-Monoiodo[125I]stearic acid and 9- or 10-monoiodo[125I]stearyl carnitine were synthesized via the isotopic exchange of 125I for cold iodine bonded to 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine.

Indium-111 labeled leukocyte imaging following hepatic artery embolization.

The use of In-111 labeled leukocytes for abscess localization is becoming well established. The first report of In-111 imaging following hepatic embolization is presented. A 45-year-old man with adenocarcinoma of the colon and metastatic liver disease was treated for intractable pain using particulate embolization of the hepatic artery. In-111 leukocyte imaging was performed to rule out abscess formation. The distribution of the labeled leukocytes demonstrated hepatic uptake commensurate with Tc-99m sulfur colloid (SC) images. Areas of embolization did not accumulate tracer. Pathologic examination at autopsy correlated with the distribution of the labeled leukocytes. Thus, therapeutic embolization did not alter the normal distribution of this tracer in functional hepatic tissue.

Microbial contamination potential of solutions in prefilled disposable syringes used with a syringe pump.

The sterility of trypticase soy broth (TSB) that was frozen and thawed in disposable plastic syringes and infused via syringe pump was studied to determine whether ambient air or personnel-transferred contaminants compromised the sterility of the solution. Samples of TSB (10, 20, 30 mL) were prepared aseptically in syringes of three different brands--150 samples for each volume (50 for each manufacturer). The syringes were placed in zip-lock bags, stored for 24 hours at -15 to -20 degrees C, and thawed for three hours. Both positive and negative controls were used. For the test samples, infusion sets were connected to the syringes under aseptic conditions, and the solution was infused via syringe pump in ambient air into polyvinyl chloride minibags before incubation. The remaining samples were prepared in the same manner as the test solutions except that they were intentionally challenged with Bacillus subtilis introduced distal to the plunger. All samples were inspected visually for turbidity after a 14-day incubation period. There was no growth in any of the test infusion samples or in samples that were intentionally contaminated. The negative controls showed no growth; all of the positive controls showed growth. The sterility of solutions frozen in disposable plastic syringes does not appear to be compromised by touch contamination of the plunger shaft or by airborne microorganisms settling on the infusion system.

Microbial contamination potential of sterile disposable plastic syringes.

The contamination potential of sterile disposable plastic syringes was evaluated after subjecting the syringes to both simulated in-use conditions and an intentional microbial challenge. Lots of 20 Luer-lock syringes in 10 or 12-cu cm and 20- or 30-cu cm sizes from three manufacturers were tested. Sampling was conducted using 30-ml vials of sterile aerobic culture media containing 14C-labeled substrates. Microbial contamination was confirmed by both visual observation of the turbidity caused by colonization and instrumental detection of 14CO2 caused by the microbial metabolism of 14C-substrates. No contamination of 120 samples was found after the ribbed plunger shaft was grasped by a bare, unprepared dry hand during five cycles of filling and injecting the medium into the vials without removing the needles from the stoppers. When this sampling technique was applied to the syringes inoculated on the upper piston surface with Bacillus subtilis suspension, a 100% contamination rate was observed in 120 samples each under both positive and negative in-vial pressure. Grasping the ribbed plunger shaft of disposable plastic syringes with a dry bare hand did not compromise the sterility of the syringe contents in this study; however, this practice should be avoided when possible. Personnel should absolutely avoid introducing fluid-borne microbial contaminants into the distal barrel end of these syringes because the contents are readily labile to contamination under these conditions.

Preparation and sterilization by filtration of Renacidin irrigation.

A method for the sterilizing filtration of Renacidin, a urologic irrigating solution, was evaluated. Renacidin irrigation was prepared and sterilized by microporous membrane filtration. A sterilizing membrane filtration apparatus was challenged by inoculating a batch of irrigation solution with Escherichia coli. The sterility of both intentionally contaminated and routinely prepared batches was evaluated. The stability of the solution was monitored by pH measurement, visual examination, maintenance of a vacuum, and absorbance spectrum of a 1:100 dilution in deionized water over a wavelength range from 400 to 200 nm. The time required to prepare three one-liter units was about two hours. No microbial growth was detected in any of the samples. The predicted minimum shelf-life at 10 degrees C was six months. Because the prepared solution contains some unreacted citric acid and bicarbonates, storage at room temperature could produce excessive pressure inside the container from carbon dioxide gas evolution. Refrigerated storage is recommended. This method for the preparation and sterilization of Renacidin irrigation is reasonably expedient, economical, and reliable.

Effect of acetaminophen on the leukocyte-labeling efficiency of indium oxine In 111.

The effect of acetaminophen on the labeling efficiency of leukocytes with indium oxine In 111 was studied. A blood sample was obtained from eight healthy men before and after they received acetaminophen 650 mg every four hours for 24 hours. After dividing the plasma from each sample into three portions, leukocytes were separated and labeled with indium oxine In 111. In an in vitro study, 200 ml of blood was obtained from one of the men, and the plasma was separated into four portions. Acetaminophen in 95% ethanol was added to three of the plasma fractions to produce acetaminophen concentrations of 4, 20, and 100 micrograms/ml; ethanol was added to the fourth fraction as a control. Each plasma fraction was then subdivided into three aliquots, and leukocytes were labeled as in the in vivo study. Mean leukocyte labeling efficiencies in both studies were calculated from the ratios of leukocyte radioactivity to initial radioactivity in the samples, expressed as percentages. Leukocyte labeling efficiencies before acetaminophen administration ranged from 79 to 85%; after administration, labeling efficiencies ranged from 70 to 87%. No significant differences in mean labeling efficiency before and after acetaminophen administration were noted in any of the subjects. Leukocyte labeling efficiencies in all in vitro plasma fractions were reduced, ranging from 54 to 63%, but no significant differences in labeling efficiency between any of the plasma fractions were found. Using the labeling procedures in this study, exposure of leukocytes from healthy men to acetaminophen in vivo or in vitro does not affect labeling efficiency with indium oxine In 111.

Effect of heparin on radioimmunoassay of gentamicin.

The effect of various heparin concentrations on the radioimmunoassay of gentamicin was studied in vitro and in rats. Heparainized test tubes were prepared, and whole blood was added followed by a gentamicin sulfate solution. Eight Sprague-Dawley rats were given heparin or gentamicin or both via infusion, and blood samples were drawn and tested. A radioimmunoassay for gentamicin was used in both the in vitro and in vivo tests. When 0-1000 units/ml of heparin were added to a constant amount of gentamicin (12 micro grams) in vitro, no difference was found in the assayed gentamicin concentration (p greater than 0.01). Similarly, when gentamicin concentrations of 0-16 micro grams /ml were added to a constant amount of heparin (20 units), the assays yielded results similar to the known gentamicin concentrations added. No significant difference was found in the clearance rate (p greater than 0.05) or terminal half-lives (p greater than 0.05) of gentamicin in treated and nontreated rats. The results suggest that variable heparin concentrations do not affect gentamicin concentrations as determined by radioimmunoassay.