Nuclear Pharmacy: An Overview

As one of the first areas in the field, nuclear pharmacy is a prototype of specialty pharmacy practice. Specialty Pharmacy Times reviews the history and some of the fundamentals of nuclear pharmacy.

History

Nuclear pharmacy has been an area of specialty pharmacy that has grown enormously over the past 50 years. Among early leaders in the field were William H. Briner and John E. Christian, who in the early 1960s, were among the first nuclear pharmacy specialists.

Early on it was clear that nuclear pharmacy needed to evolve into an area of specialty pharmacy practice. For instance, many radiopharmaceuticals have an extremely short half-life, therefore these products must be prepared and verified for potency soon before the patient receives the treatment.

These pioneers of nuclear pharmacy published the first radiopharmaceutical monographs in the fifteenth revision of the United States Pharmacopoeia in 1955. They were soon joined, however, by a growing group of specialists who maintained a network of professional contacts that ultimately became the basis for further growth of the field. By the early 1970s, pharmacist involvement in radiopharmaceuticals broadened as pharmacy schools established formal training programs for niche pharmacy practice areas, including programs for nuclear pharmacy specialists.

By 1975, the American Pharmacists Association (APhA) had recognized nuclear pharmacy as an area of specialty practice. With this recognition came the first set of guidelines governing the practice of nuclear pharmacy. Development of these guidelines were soon followed by a test establishing board certification in nuclear pharmacy (BCNP) qualification. In 1982, 63 pharmacists had attained board certification in nuclear pharmacy (BCNP), and by 1998 more than 430 BCNPs were practicing in the United States.

Training Requirements

The Nuclear Regulatory Commission (NRC) requires certain training standards from any authorized nuclear pharmacists. In addition to the usual qualifications of a pharmacist, nuclear pharmacists are required to have a specialty board certification in nuclear pharmacy, including successful completion of a board certification exam and (with a few exceptions) at least 4000 hours of training in the area of nuclear pharmacy practice.

In preparing, shipping, receiving, and preparing radiopharmaceuticals, pharmacists must follow stringent operating standards, including regular checks of radiation levels. During compounding of radiopharmaceutical products, nuclear pharmacists adhere to quality assurance standards and radiation safety standards. Nuclear pharmacists are also expected to be familiar with the physics and mathematics of radiation and must be able to calibrate, maintain, and operate instrumentation used to measure radiation levels.

Generation of Radiopharmaceuticals

In the production of radiopharmaceuticals, nuclear pharmacists will often make use of a device for carrying out nuclear reactions known as a cyclotron. The cyclotron accelerates charged particles, including protons and deuterons, in a vacuum.

When accelerated, the particles gain energy and velocity under the influence of a magnetic field. These high-energy particles are then directed toward a stable element, enabling nuclear reactions and transformations to occur. Through proper use of the cyclotron, it is possible to produce radioactive drugs in a safe manner.

Nuclear pharmacists also produce radioactive drugs with a radionuclide generator. The generator contains a long-lived nuclide that undergoes decay over time. In the process of decay, the long-lived nuclide forms short-lived daughter nuclides, which are often used in imaging procedures. The short half-life of these imaging agents reduce radiation exposure to patients, but also make storage and transport of the radioactive imaging agents difficult.

Radionuclide generators make it possible to produce short-lived radionuclides in or near the institution where they are used. Using the generator requires careful sanitary procedures, including autoclaving and use of bacteriostatic agents. In addition, all equipment is subject to stringent recordkeeping requirements and regular quality testing.

Layout of a Nuclear Pharmacy

In general, the smallest possible nuclear pharmacy measures 4 meters in length and 4 meters in width, although larger operations may include several rooms, including a health physics area, a high-radiation area, a compounding area, a storage area, and a dispensing area that is separated from all other locations.

Pharmacists and technicians follow stringent procedures and regulations designed to protect themselves and the public from the hazards of radiation. For instance, nuclear pharmacists make use of special fume hoods capable of filtering radioactive gasses, as well as lead-lined containers, vials, and syringes to reduce the risk of radiation-related harm.

For further protection, pharmacists may also wear lead-lined aprons, gloves, and eyeglasses during compounding and dispensing duties. Proper lot numbering, labeling, and tracking of all materials that go in and out of a pharmacy helps protect the public from radioactive material from getting into the wrong hands.

Specific Radiopharmaceutical Products

Radiopharmaceuticals have a variety of uses in both imaging and as active therapeutic treatments across a wide range of medical conditions including cancers, thyroid conditions, and polycythemia vera.

In patients with hyperthyroidism, thyroid irradiation with radioactive iodine (I-131) enables destruction of hyperactive thyroid tissue. Radioactive iodine, which accumulates in the thyroid tissue, may also act as a targeted treatment against thyroid cancers.

Radiopharmaceuticals may also be helpful in treating bone pain associated with certain cancers, such as multiple myeloma, and cancers of other sites that have metastasized to bone tissue. For instance, drugs containing radioactive strontium and samarium, as well as treatments with radioactive phosphorous-containing compounds may help destroy malignant cells in bone tissue and reduce the severity of bone pain. Some dose-limiting adverse events associated with these treatments involve toxicity to bone tissue, including bone marrow.

In patients with unresectable hepatocellular carcinoma, ⁹⁰Y-TheraSphere is one available treatment. This radioactive medication becomes lodged in cancer tissue and emits beta radiation that helps kill tumor cells.

Treatment is often associated with abnormal liver enzyme levels and may also result in the death of some healthy liver tissue. Abdominal pain, nausea, vomiting, and diarrhea are other common adverse events associated with the treatment, although more serious adverse events due to radiation exposure may occur, including acute pancreatitis, radiation pneumonitis, radiation hepatitis, and acute cholecystitis.

In patients with non-Hodgkin's lymphoma, radiopharmaceuticals include ⁹⁰Y-ibritumomab tiuxetan (Zevalin) and ¹³¹I-tositumomab (Bexxar).

Zevalin, which is an anti-CD20 antibody, may be used in relapsed or refractory low-grade B-cell non-Hodgkin's lymphoma expressing CD20 antigens. When used with rituximab, Zevalin may aid in reducing tumor mass, although it is associated with side effects that include flu-like symptoms and cytopenias.

Bexxar is a radiopharmaceutical used for low-grade, follicular non-Hodgkin's lymphoma expressing CD20 receptors. Treatment is individualized for each patient through radiation-based imaging and calculation of the appropriate dosage. Bexxar is contraindicated in pregnant women, and the radiation dosage delivered must be adjusted based on platelet counts.

In patients with polycythemia vera—a disease of increased bone marrow activity and excess red blood cell production—³²P-sodium orthophosphate may help reduce red blood cell mass when used in combination with phlebotomy. Treatment is limited based platelet levels, and dosing must be adjusted based on neutrophil counts.

Nuclear Pharmacy: In Summary

Nuclear pharmacy is an important specialty pharmacy practice site and is a prototype for further developments in the field. The specialized training and board certification associated with nuclear pharmacy reflects the important responsibilities of the specialized pharmacist.

One hundred years ago, the practice of medicine was primarily a field of generalists. Today, medicine has shifted to a field of specialists. Pharmacy is undergoing the same transformation. As more medications become available, including specialized targeted therapies that are only effective in certain subsets of patients, therapeutic specialization in pharmacy is becoming increasingly important.

Nuclear pharmacy is an early example of board certification and specialization. Because nuclear pharmacists deal with a specialized range of products, this specialization helps protect the safety of patients and the public. A growing range of board-certified specializations in pharmacy, including ambulatory care, critical care, nutrition support, oncology, pediatrics, and psychiatry will become increasingly important to the ongoing specialization of the field.

References:

• Shaw SM, Ice RD. Nuclear pharmacy, Part I: Emergence of the specialty of nuclear pharmacy. J Nucl Med Technol. 2000;28(1):8-11.
• United States Nuclear Regulatory Commission. Training for an authorized nuclear pharmacist. http://www.nrc.gov/reading-rm/doc-collections/cfr/part035/part035-0055.html. Accessed October 2014.
• Saha GB. Fundamentals of Nuclear Pharmacy. 6th Edition. Cleveland, OH: Springer; 2010.
• Board of Pharmacy Specialties. http://www.bpsweb.org/about/councils.cfm. Accessed October 2014.