Changes in Patterns of 99mTc-Macroaggregated Albumin Use Between 2000 and 2015.

Since the early 2000s, the method of evaluating pulmonary embolism has shifted from 99mTc-macroaggregated albumin (MAA) perfusion lung scans to CT angiography. 99mTc-MAA continues to be applied for patients with contraindications to CT angiography and for other uses. A reduced number of 99mTc-MAA particles is administered to patients with pulmonary hypertension or other risk factors. This study assessed the changing patterns of 99mTc-MAA use between 2000 and 2015 at a single institution by comparing snapshots of the procedures performed in those two years. Methods: Records for all patients receiving 99mTc-MAA in 2000 and 2015 were reviewed, making note of the type of imaging procedure, whether there was any contraindication to CT angiography, and whether a reduced number of 99mTc-MAA particles was administered. Results: In 2000, 99mTc-MAA was used for 489 lung scans for pulmonary embolism, 2 for peritoneovenous shunts, and 1 for a cardiac shunt. Of the lung scan patients, 46 (9%) had pulmonary hypertension. A reduced number of particles was administered to the pulmonary hypertension and cardiac shunt patients (47/492, or 9%). In 2015, 99mTc-MAA was used for 263 lung scans for pulmonary embolism, 33 for presurgical planning, 33 for patients with a lung transplant, 16 for pulmonary artery stenosis, 5 to determine hepatic artery microsphere eligibility, and 1 for a peritoneovenous shunt. Of the lung scans for pulmonary embolism, 256 of the 263 patients (97%) had a contraindication to CT angiography or a nondiagnostic CT angiogram, including 99 (38%) with pulmonary hypertension. A reduced number of particles was administered to the pulmonary hypertension patients, presurgical patients, and lung-transplant patients (165/351, or 47%). Conclusion: Comparing 2015 with 2000, lung scans for pulmonary embolism decreased 46%, from 489 to 263, apparently because of a shift to CT angiography, whereas other uses rose from 3 to 88. Administration of a reduced number of particles rose significantly from 9% to 47% of 99mTc-MAA doses. Although the total number of 99mTc-MAA doses dropped 29%, from 492 to 351, 99mTc-MAA remains an important radiopharmaceutical for both pulmonary embolism and other uses.

Liquid gastric emptying as an adjunct to hepatobiliary scintigraphy when oral corn oil is used as a cholecystagogue for determining gallbladder emptying.

UNLABELLED: During times of sincalide shortage, a fatty meal can be used to stimulate gallbladder contraction during hepatobiliary scintigraphy. However, if a patient has an abnormal gallbladder ejection fraction (GBEF), is the cause chronic cholecystitis or is it inadequate cholecystokinin stimulation due to poor gastric emptying? Hence, during the 2014 sincalide shortage, simultaneous liquid gastric emptying using (99m)Tc-sulfur colloid along with corn oil emulsion was initiated as routine practice in patients evaluated for GBEF. The objective of this study was to retrospectively assess the time course of gastric emptying in these patients, especially with regard to whether delayed gastric emptying may be a factor in some patients with a poor GBEF. METHODS: My institution's clinical imaging procedure during the 2014 sincalide shortage consisted of routine (99m)Tc-mebrofenin hepatobiliary scintigraphy followed by corn oil emulsion and (99m)Tc-sulfur colloid orally. Dynamic imaging with regions of interest encompassing the gallbladder and the stomach allowed determination of GBEF and gastric emptying. For this study, the imaging records for 53 consecutive patients undergoing this clinical procedure were reviewed. The time for half gastric emptying, along with percentage gastric emptying at the end of imaging, was evaluated in relationship to GBEF. RESULTS: Seventeen patients had a normal GBEF (74% ± 14%) and satisfactory gastric emptying (31 ± 21 min for half emptying, 75% ± 14% emptying at end of imaging); 17 patients had a normal GBEF (77% ± 17%) despite unsatisfactory gastric emptying (only 30% ± 14% emptying at end of imaging); 5 patients had an abnormal GBEF (19% ± 9%) and satisfactory gastric emptying (26 ± 19 min for half emptying, 82% ± 14% emptying at end of imaging), supporting a diagnosis of chronic cholecystitis; 11 patients had an abnormal GBEF (26% ± 9%) but also unsatisfactory gastric emptying (only 26% ± 13% emptying at end of imaging), which did offer additional support for a diagnosis of chronic cholecystitis; and 3 patients had a borderline GBEF (40% ± 2%) with satisfactory gastric emptying (59% ± 6% emptying at end of imaging). CONCLUSION: Simultaneous liquid gastric emptying can provide additional information in the interpretation of GBEF when a fatty meal is used as an oral cholecystagogue, especially to help differentiate chronic cholecystitis from inadequate cholecystokinin stimulation due to poor gastric emptying.

Use of radiopharmaceuticals in diagnostic nuclear medicine in the United States: 1960-2010.

To reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, the authors assessed which radiopharmaceuticals were used in different time periods, their relative frequency of use, and typical values of the administered activity. This paper presents data on the changing patterns of clinical use of radiopharmaceuticals and documents the range of activity administered to adult patients undergoing diagnostic nuclear medicine procedures in the U.S. between 1960 and 2010. Data are presented for 15 diagnostic imaging procedures that include thyroid scan and thyroid uptake; brain scan; brain blood flow; lung perfusion and ventilation; bone, liver, hepatobiliary, bone marrow, pancreas, and kidney scans; cardiac imaging procedures; tumor localization studies; localization of gastrointestinal bleeding; and non-imaging studies of blood volume and iron metabolism. Data on the relative use of radiopharmaceuticals were collected using key informant interviews and comprehensive literature reviews of typical administered activities of these diagnostic nuclear medicine studies. Responses of key informants on relative use of radiopharmaceuticals are in agreement with published literature. Results of this study will be used for retrospective reconstruction of occupational and personal medical radiation doses from diagnostic radiopharmaceuticals to members of the U.S. radiologic technologists' cohort and in reconstructing radiation doses from occupational or patient radiation exposures to other U.S. workers or patient populations.

Absorbed radiation doses to staff after implementation of a radiopharmacy clean room.

UNLABELLED: In response to U.S. Pharmacopeia general chapter <797> standards, a clean room was constructed for our in-house radiopharmacy. Previously, most patient doses were prepared as needed just before injection. Currently, to minimize repeated entries into the clean room, most patient doses are prepared in batches; that is, early morning and noontime preparation of doses to be injected at various times throughout the morning and the afternoon, respectively. Because these patient doses may be prepared well before injection time, radioactive decay necessitates higher amounts of radioactivity to be handled for patient dose preparation. Hence, absorbed radiation doses to staff, all of whom rotate into the radiopharmacy clean room in addition to their regular patient-related activities, were retrospectively evaluated. METHODS: Monthly dosimetry reports for body (chest badge) and extremities (finger ring) were retrospectively reviewed for each staff member for 12 mo before and 12 mo after implementation of the radiopharmacy clean room. Monthly data were evaluated for average and SD, and 12-mo groups were evaluated using a paired t test. Data for the second 12-mo period were also normalized to the same number of patient doses to account for an increase in procedure volume and were reevaluated. RESULTS: Before the radiopharmacy clean room had been implemented, average monthly absorbed radiation doses to body and extremities were 23 ± 15 mrem (0.23 ± 0.15 mSv) and 93 ± 59 mrem (0.93 ± 0.59 mSv), respectively. After the clean room had been implemented, average monthly absorbed radiation doses increased to 32 ± 16 mrem (0.32 ± 0.16 mSv) (P < 0.001) and 121 ± 89 mrem (1.21 ± 0.89 mSv) (P = 0.0015), respectively. When normalized for procedure volume, average monthly absorbed radiation doses after implementation of the clean room were still higher, at 29 ± 15 mrem (0.29 ± 0.15 mSv) (P = 0.001) and 110 ± 80 mrem (1.10 ± 0.80 mSv) (P = 0.039), respectively. CONCLUSION: After implementation of a radiopharmacy clean room, absorbed radiation doses to body and extremities increased by 26% and 18%, respectively, even after normalizing for procedure volume. Because absorbed radiation doses from other activities, such as patient dose administration and patient imaging, are assumed to remain relatively constant, these increases in absorbed radiation doses to staff are attributed to changes in work flow after implementation of the radiopharmacy clean room.

Technetium Tc-99m pyrophosphate for cerebrospinal fluid leaks: radiopharmaceutical considerations.

OBJECTIVE To confirm the anticipated image quality and absence of adverse reactions in patients undergoing clinical practice cerebrospinal fluid (CSF) leak imaging procedures using technetium Tc-99m pyrophosphate (PYP). METHODS Following the recent discontinuation of preservative-free calcium trisodium diethylene triamine pentaacetic acid kits, PYP was selected as a suitable alternative for CSF leak imaging procedures. Procedures were established for its preparation and dispensing, paying special attention to safety considerations, and its use in clinical practice was implemented. Medical records, including images, were reviewed for the first 15 patients undergoing clinical practice CSF imaging procedures using Tc-99m PYP to confirm anticipated image quality and absence of adverse effects. RESULTS Review of CSF leak imaging procedures using Tc-99m PYP in 15 patients showed images to be of uniformly high quality. The vast majority of injected radiopharmaceutical remained in the CSF throughout the duration of the imaging procedure, allowing visualization of CSF leaks. Only a small amount of Tc-99m PYP diffused into the blood with resultant uptake on the skeleton and excretion into the urine, which did not interfere with image interpretation. No adverse reactions were noted in any of the patients. CONCLUSION With proper attention to safety considerations, Tc-99m PYP is a safe and effective alternative for performing CSF leak imaging procedures.

Self-sealing capacity of vial stoppers after multiple needle punctures.

OBJECTIVE: To evaluate the self-sealing capacity of vial stoppers in two common radiopharmaceuticals after more than 10 needle punctures. METHODS: Assessment of self-sealing capacity was performed according to the self-sealing capacity test described in United States Pharmacopeial Convention (USP) General Chapter <381>. Groups of 10 vials of technetium (Tc)-99m sulfur colloid and Tc-99m tetrofosmin were tested for maintenance of self-sealing capacity following 10 punctures with 22-, 20-, and 18-gauge needles. Each vial was sequentially retested after additional sets of 10 punctures until failure of self-sealing capacity or until a total of 100 punctures, whichever came first. RESULTS: The median number of needle punctures with maintenance of self-sealing ability before failure for 22-, 20-, and 18-gauge needles was >100 (range all >100), >100 (all >100), and 60 (30-90), respectively, for sulfur colloid and >100 (all >100), >100 (50 to >100), and 50 (20-70), respectively, for tetrofosmin. Incidentally, coring particles were observed frequently in vials after many punctures with 18-gauge needles, but infrequently with 20-gauge and rarely with 22-gauge needles. CONCLUSION: Vial stoppers in two radiopharmaceutical products demonstrated robust self-sealing capacity, substantially exceeding the USP standard of 10 punctures with a 21-gauge needle. Coring particles were frequently observed after many punctures when using larger-bore needles but rarely when using smaller-bore needles. Under conditions commonly used, failure of self-sealing capacity and generation of coring particles are not anticipated to be problems encountered when puncturing vial stoppers of these two products substantially more than 10 times.

Evaluation of alternative methods for radiochemical purity testing of indium-111 capromab pendetide.

OBJECTIVE: To evaluate alternative methods for radiochemical purity testing of indium (In)-111 capromab pendetide after the discontinuation of instant thin-layer chromatography silica gel (ITLC-SG) strips. DESIGN: Descriptive experimental study. SETTING: United States in 2009. PARTICIPANTS: Not applicable. INTERVENTION: Paper chromatography using Whatman 3MM strips, paper chromatography using Whatman 31ET strips, and mini-column chromatography using silica Sep-Pak cartridges were evaluated in the radiochemical purity testing of 13 consecutive vials of In-111 capromab pendetide prepared for clinical patient imaging procedures. These methods also were evaluated by testing seven aliquots of In-111 capromab pendetide that had been spiked with 5% to 15% In-111 pentetate (diethylene triamine pentaacetic acid). MAIN OUTCOME MEASURES: Correlation coefficients, radiochemical purity values for each method compared with ITLC-SG, and procedure times. RESULTS: Correlation coefficients of 0.988, 0.996, and 0.979 were found for ITLC-SG compared with Whatman 3MM, Whatman 31ET, and silica Sep-Pak, respectively. Compared with ITLC-SG, mean (±SD) radiochemical purity values differed by -0.8 ± 0.8 (range -2.5 to 0.4) for Whatman 3MM, -0.8 ± 0.6 (-2.3 to 0) for Whatman 31ET, and -0.5 ± 1.2 (-3.6 to 0.7) for silica Sep-Pak. The approximate time required to develop the chromatography strip or elute the mini-column was 3, 14, 5, and 6 minutes for ITLC-SG, Whatman 3MM, Whatman 31ET, and silica Sep-Pak, respectively. CONCLUSION: All three methods evaluated were acceptable alternatives to ITLC-SG for radiochemical purity testing of In-111 capromab pendetide. Based on its slightly higher correlation to ITLC-SG, slightly tighter SD and range, and slightly shorter development time, Whatman 31ET is preferred in our facility.

Radiopharmaceutical considerations for using Tc-99m MAA in lung transplant patients.

OBJECTIVES: To elucidate radiopharmaceutical considerations for using technetium Tc-99m albumin aggregated (Tc-99m MAA) in lung transplant patients and to establish an appropriate routine dose and preparation procedure. SETTING: Tertiary care academic hospital during May 2007 to May 2009. PRACTICE DESCRIPTION: Nuclear pharmacist working in nuclear medicine department. PRACTICE INNOVATION: Radiopharmaceutical considerations deemed important for the use of Tc-99m MAA in lung transplant patients included radioactivity dose, particulate dose, rate of the radiolabeling reaction (preparation time), and final radiochemical purity. Evaluation of our initial 12-month experience, published literature, and professional practice guidelines provided the basis for establishing an appropriate dose and preparation procedure of Tc-99m MAA for use in lung transplant patients. MAIN OUTCOME MEASURES: Radiochemical purity at typical incubation times and image quality in subsequent lung transplant patients imaged during the next 12 months. RESULTS: Based on considerations of radioactivity dose, particulate dose, rate of the radiolabeling reaction (preparation time), and final radiochemical purity, a routine dose consisting of 3 mCi (111 MBq) and 100,000 particles of Tc-99m MAA for planar perfusion lung imaging of adult lung transplant patients was established as reasonable and appropriate. MAA kits were prepared with a more reasonable amount of Tc-99m and yielded high radiochemical purity values in typical incubation times. Images have continued to be of high diagnostic quality. CONCLUSION: Tc-99m MAA used for lung transplant imaging can be readily prepared with high radiochemical purity to provide a dose of 3 mCi (111 GBq)/100,000 particles, which provides images of high diagnostic quality.

Special safety considerations in preparation of technetium Tc-99m DTPA for cerebrospinal fluid-related imaging procedures.

OBJECTIVE: To review special safety considerations in the preparation of technetium 99m (Tc-99m) diethylenetriaminepentaacetic acid (DTPA; generic name, pentetate) for cerebrospinal fluid (CSF)-related imaging procedures. DATA SOURCES: Review of practices and results at one institution supplemented with findings and recommendations from the literature. Literature searches were conducted via Medline/PubMed using the following terms: Tc-99m DTPA/pentetate, CSF, cisternography, intrathecal, and adverse reactions. The author's own files were also searched for articles (e.g., in newsletters) not indexed by Medline/PubMed. STUDY SELECTION: Articles considered appropriate for review included all human research studies, reviews, case reports, abstracts, and letters published in English on Tc-99m DTPA use in CSF-related imaging procedures, especially with regard to safety or adverse reactions. DATA EXTRACTION: All information related to safety precautions and adverse reactions associated with Tc-99m DTPA injected intrathecally or otherwise used for CSF-related imaging procedures were considered. DATA SYNTHESIS: 18 years' experience in one institution was reviewed with the added perspective of literature findings and recommendations. CONCLUSION: With proper attention to safety considerations, Tc-99m DTPA can be safely used in CSF-related imaging procedures.

A performance evaluation of 90Y dose-calibrator measurements in nuclear pharmacies and clinics in the United States.

A blind performance test was conducted to evaluate dose-calibrator measurements at nuclear pharmacies in the United States (US). Two test-sample geometries were chosen to represent those used for measurements of 90Y-ibritumomab tiuxetan (ZEVALIN). The radioactivity concentration of test-samples was verified by the US National Institute of Standards and Technology. Forty-five results were reported by 10 participants. Eighty percent of reported values were within the US Pharmacopoeia content standard (+/-10%) for 90Y-ZEVALIN. All results were within US Nuclear Regulatory Commission conformance limits (+/-20%) for defining therapeutic misadministrations.

Effect of solvent flow rate in mini-column testing of 99mTc-mertiatide.

OBJECTIVE: The recommended method for radiochemical purity testing of 99mTc-mertiatide involves the use of a C-18 solid-phase mini-column cartridge. The mertiatide package insert states that the solvents should be "pushed through the cartridge slowly," but a flow rate is not specified. The mini-column cartridge instruction sheet recommends flow rates of 5-10 and 2-10 mL/min for conditioning and for elution, respectively, of the cartridge. The purpose of this study was to evaluate the effect of different flow rates on determining the radiochemical purity of 99mTc-mertiatide. METHODS: Radiochemical purity was tested on 10 consecutive vials of 99mTc-mertiatide prepared for routine clinical use and on 4 vials of 99mTc-mertiatide spiked with 6%-15% free pertechnetate using 3 different flow rates: slow drip (5 mL/min for conditioning and 2 mL/min for elution), fast drip (10 mL/min for conditioning and 10 mL/min for elution), and very fast drip (about 15-20 mL/min for conditioning and about 15-20 mL/min for elution). An infusion pump was used to provide constant flow rates for the first 2 conditions, whereas manual handling, reflecting real-life practice, was used for the third condition. RESULTS: All 3 flow rates yielded essentially identical radiochemical purities for each vial tested (agreement was always within 0.3% for a given vial). The elapsed times for mini-column conditioning, loading, and elution were approximately 15, 5, and 3 min for the slow drip, fast drip, and very fast drip, respectively. CONCLUSION: Faster flow rates for mini-column testing of 99mTc-mertiatide save time (and correspondingly reduce radiation exposure to the worker) without adversely affecting the results of radiochemical purity determinations.

Corn oil emulsion: a simple cholecystagogue for diagnosis of chronic acalculous cholecystitis.

UNLABELLED: This study investigated the use of a corn oil emulsion as an inexpensive alternative to sincalide in the scintigraphic diagnosis of chronic acalculous cholecystitis (CAC). METHODS: Thirty patients with abdominal or right upper quadrant pain underwent (99m)Tc-disofenin hepatobiliary imaging for 60 min. After gallbladder filling, 30 mL of corn oil emulsion were administered orally to all patients followed by dynamic imaging for an additional 60 min in all patients and for 90 min in 26 patients. Gallbladder emptying kinetics were determined with gallbladder ejection fractions calculated at 30, 60, and 90 min. The results were compared with histopathologic or clinical follow-up data. RESULTS: Corn oil emulsion was found to be palatable and free of side effects in all patients. Seven of the 30 patients had histopathologic evidence of CAC, whereas the remaining 23 did not have evidence of gallbladder disease based on clinical follow-up. The 30-, 60-, and 90-min gallbladder ejection fractions were determined to be 25% +/- 22% (mean +/- SD), 47% +/- 28%, and 62% +/- 29%, respectively. Receiver-operating-characteristic analysis showed that the 60-min gallbladder ejection fraction best distinguished between CAC and non-gallbladder disease with an area under the curve of 0.963. A 60-min gallbladder ejection fraction of < or = 20% had 100% sensitivity, 96% specificity, 88% positive predictive value, 100% negative predictive value, and 97% overall accuracy for the diagnosis of CAC. CONCLUSION: Standardized corn oil emulsion appears to be an adequate and well-tolerated gallbladder stimulant. Based on receiver-operating-characteristic analysis, a 60-min gallbladder ejection fraction of < or = 20% using this simple cholecystagogue results in high diagnostic accuracy for CAC.

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.