Nuclear pharmacy, Part II: Nuclear pharmacy practice today.

OBJECTIVE: Nuclear pharmacy is a specialty within the profession of pharmacy that focuses on the proper use of radiopharmaceuticals. This article reviews various features of contemporary nuclear pharmacy practice. After reading this article the nuclear medicine technologist should be able to: (a) describe nuclear pharmacy training and certification; (b) discuss nuclear pharmacy practice settings; (c) discuss nuclear pharmacy practice activities; (d) list professional organizations; and (e) describe activities associated with job satisfaction. In addition, the reader should be able to discuss regulatory issues of current concern.

The AAPM/RSNA physics tutorial for residents. Radiopharmaceuticals.

Radiopharmaceuticals are essential to the performance of nuclear medicine procedures. These radioactive drugs consist of two components: a drug component for localization in a specific tissue or organ and a radioactive component for diagnostic or therapeutic purposes. The majority of radiopharmaceuticals are used for diagnostic imaging procedures. The radioisotopes used for radiopharmaceuticals are produced in a number of ways: as by-products of fission, by means of neutron activation, by cyclotrons, and by generators. These methods produce isotopes with both desirable and undesirable properties. Approximately 80% of all nuclear medicine procedures performed in the United States use radiopharmaceuticals labeled with technetium-99m. The chemical properties of technetium allow relatively simple preparation of Tc-99m compounds by using reagent kits. Quality control testing of radiopharmaceuticals is routinely performed to ensure compliance with various purity standards such as assay for radioactivity, radionuclidic purity, chemical purity, radiochemical purity, pharmaceutical purity, and biologic purity.

Technetium-99m radiopharmaceutical preparation problems: 12 years of experience.

OBJECTIVE: Chemical reactions involved in preparing 99mTc radiopharmaceuticals occasionally result in products of substandard purity. A retrospective examination of preparation problems that occurred in the author's institution was conducted to better define the incidence, recognize patterns and identify causes of substandard 99mTc radiopharmaceutical products. METHODS: All 99mTc radiopharmaceutical preparation and quality control testing records for the years 1986-1997 were reviewed, and preparation factors associated with substandard products were identified and examined. RESULTS: Fifty of 20,972 (0.2%) 99mTc products had substandard radiochemical purity; none were administered to patients. Twenty-eight of the 50 substandard products (56%) involved macroaggregated albumin with the remainder divided among in vitro red blood cells, exametazime, disofenin, sestamibi, mertiatide and sulfur colloid. Thirty-three of the 50 (66%) involved 99mTc-pertechnetate obtained as the first elution of a new generator and/or 99mTc-pertechnetate more than 12 hr old. Several of the substandard products involved other preparation factors and/or human error. CONCLUSION: The majority of substandard 99mTc radiopharmaceutical products involved the use of 99mTc-pertechnetate containing excessive amounts of 99Tc and/or oxidizing impurities to prepare products containing relatively small amounts of stannous. Although substandard products are an infrequent occurrence, radiochemical purity testing should be performed routinely on all 99mTc radiopharmaceuticals before patient administration.

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.

Dosimetry of [15O]water: a physiologic approach.

Earlier dosimetry estimates for [15O]water assumed its instantaneous equilibrium with total body water. This assumption leads to an underestimation of the absorbed doses to organs with high blood flows, since the biodistribution of this short-lived radiopharmaceutical is dependent upon blood flow to organs. We have developed a physiologically based whole body blood flow model (WBBFM) using a commercially available icon-driven mathematical simulation software package and applied it to the reevaluation of [15O]water dosimetry in humans. The WBBFM uses multiple parallel compartments to represent organs, heart chambers, the injection site for [15O]water, and blood sampling sites (arterial and venous). Input values to the WBBFM include organ blood flows, organ masses, organ water volumes, organ:blood partition coefficients, injected activity and S-values of [15O]. The WBBFM is based on the same assumptions that are used in calculating regional blood flow using [15O]water and simulates the human body closely in its physiologic response. The activity in each organ is derived from the simulation and is used to calculate absorbed doses. The WBBFM calculated absorbed doses in microGy/MBq (mrad/mCi) to various organs are as follows: heart--2.66 (9.84), kidneys--2.20 (8.15), thyroid--1.83 (6.78), brain--1.66 (6.13), ovaries--1.25 (4.61), breast--1.24 (4.59), and small intestine--1.03 (3.83). These values are approximately two- to threefold higher than the earlier estimates of Kearfott [J. Nucl. Med. 23, 1031-1037 (1982)] and similar to the recent findings of Herscovitch et al. [J. Nucl. Med. 34, 155P (1983)]. We believe this approach yields more realistic dosimetry estimates for [15O]water. Accordingly, we have revised the amount of [15O]water administered during regional blood flow studies at our institution. The relative ease and accuracy of this approach suggests its usefulness in dosimetry estimation for other freely diffusible radiopharmaceuticals.

Analysis of the practice of nutrition support pharmacy specialists.

In 1988 the Board of Pharmaceutical Specialities (BPS) recognized nutrition support pharmacy practice (NSPP) as one of four specialty areas in pharmacy. The BPS appointed a specialty council to develop and manage the process for board certification of qualified specialists. One step was to identify and validate activities performed by the specialists. This was accomplished by conducting a study that delineated the role of these practitioners and also provided information for developing a blueprint for a certification examination. The results revealed the types of practice settings, education, and training for specialists, and the distribution of professional time devoted to nutrition support activities.

Diuretic-enhanced I-131 clearance after ablation therapy for differentiated thyroid cancer.

The authors assessed whether the whole-body radiation burden can be reduced with diuretic enhancement of iodine-131 excretion in patients with thyroid cancer and slow clearance. Whole-body imaging and quantitative I-131 clearance data obtained before and after ablation therapy were evaluated in 56 patients. Fourteen patients with slow pre-ablation therapy clearance (> 50% retention at 24 hours) received oral diuretics after I-131 therapy. Nine patients began taking furosemide 24 hours after I-131 treatment. Five patients had been receiving thiazide diuretics and were continued on the same dose after treatment. The mean half-time of I-131 clearance for the patients treated with furosemide decreased by 12 hours (P < .05) but was not significantly decreased for those who received thiazides or for the patients who did not receive diuretics. Administration of diuretics can improve I-131 clearance in patients with thyroid cancer and slow clearance, reducing the radiation burden and shortening the hospital stay.

Lidocaine and dextran sulfate inhibit leukocyte accumulation but not postischemic contractile dysfunction in a canine model.

Leukocytes have been implicated as a possible factor in the pathogenesis of postischemic contractile dysfunction, probably through the release of oxygen free radicals. Lidocaine and dextran sulfate are known to inhibit leukocyte adherence to endothelial cells in vitro and in vivo. In an acute open-chest canine model both agents were found to inhibit the augmented accumulation of indium-111-labeled leukocytes in briefly ischemic and subsequently reperfused myocardium. Pharmacologic inhibition of leukocyte accumulation by lidocaine and dextran sulfate, however, was not associated with improvement in postischemic contractile dysfunction.

Uses and limitations of positron emission tomography in clinical pharmacokinetics/dynamics (Part II).

Positron emission tomography (PET) involves imaging the biodistribution and tissue localisation of small amounts of radiolabelled biomolecules or drugs. In Part I of this article, which appeared in the previous issue of the Journal, the applications of pharmacokinetics in PET were discussed in order to derive quantitative measures of physiological function. Part II examines the use of PET imaging as a tool to study the pharmacokinetics and pharmacodynamics of specific drugs.

Uses and limitations of positron emission tomography in clinical pharmacokinetics/dynamics (Part I).

Positron emission tomography (PET) involves imaging the biodistribution and tissue localisation of small amounts of radiolabelled biomolecules or drugs. In Part I of this article, the applications of pharmacokinetics in PET are discussed in order to derive quantitative measures of physiological function. Part II will examine the use of PET imaging as a tool to study the pharmacokinetics and pharmacodynamics of specific drugs.

Postoperative bone marrow alterations: potential pitfalls in the diagnosis of osteomyelitis with In-111-labeled leukocyte scintigraphy.

Scintigraphy was used after injection of technetium-99m methylene diphosphonate (MDP) and indium-111-labeled white blood cells (WBCs) to assess for the presence of osteomyelitis in 97 patients who had undergone prior surgical procedures. Thirty-four patients with abnormal In-111-labeled WBC patterns underwent restudy with Tc-99m albumin colloid (AC). Scintigraphic findings were considered positive for osteomyelitis whenever localization of In-111-labeled WBCs exceeded Tc-99m AC activity in extent or focal intensity (discordant pattern). Ten of 12 patients with culture-proved osteomyelitis had discordant patterns; two had false-negative (concordant) patterns. The cases of 20 of 22 patients without infection who were considered to have osteomyelitis on the basis of patterns of In-111-labeled WBCs and Tc-99m MDP were reclassified correctly on the basis of concordant patterns of In-111-labeled WBCs and Tc-99m AC. Radiocolloid images improved the overall scintigraphic specificity for osteomyelitis from 59% without bone marrow imaging to 92%; sensitivity decreased from 94% to 88%.

Effect of pertechnetate source and age on the radiochemical purity of technetium Tc 99m exametazime.

The radiochemical purity of technetium Tc 99m exametazime preparations was evaluated by comparing pertechnetate sources and sodium pertechnetate Tc 99m ages. Vials of exametazime were prepared using sodium pertechnetate Tc 99m that was obtained from two brands of generators and up to five hours after elution. Radiochemical purity was determined by using instant thin-layer chromatography. Substantial variability in radiochemical purity existed within and between lots of exametazime. There was little difference in radiochemical purity between the two brands of generator and among the various ages of eluant. The radiochemical purity was not significantly affected by the source or age of sodium pertechnetate Tc 99m used in this study.