Nuclear pharmacy is a specialized practice area in pharmacy that involves compounding and dispensing radiopharmaceuticals to be used in various nuclear medicine procedures. Unlike radiology, nuclear medicine is a fantastic tool for assessing physiology (function), as opposed to only structure and anatomy.
It is a unique niche within pharmacy and this article will provide an overview of the specialty area, including common radiopharmaceuticals and procedures used in nuclear medicine, as well as the role of a nuclear pharmacist on the healthcare team.
From a business perspective, the industry’s current standing includes nuclear pharmacies which are either institutional (and cater to a single medical center), or commercial. Centralized commercial pharmacies are contracted by hospitals/clinics to provide radiopharmaceuticals.
Today, there are only a few major radiopharmacies: GE (formerly known as Amersham), Covidien (formerly known as Tyco or Mallinckrodt), and Cardinal Health (which bought out Syncor, among others), as well as a few smaller independents.
Tc-99m and Compounding Radiopharmaceuticals
Technetium (Tc-99m) is by far the predominant isotope used; it is an ideal diagnostic tracer and is used to compound the vast majority of radiopharmaceuticals.
To put it very simply, Tc-99m is obtained by eluting a molybdenum generator: a vial of saline is placed at the entry point of the generator, with an evacuated vial on the opposite end (encased by a heavy tungsten shield). The negative pressure draws the saline through the generator, and a sodium pertechnetate eluate is produced.
Depending on the amount of activity needed for the run (and the number of doses the pharmacy will send out), several generators are hit throughout the course of the day. This Tc-99m elution is then used to compound the majority of kits in the pharmacy. Since Tc-99m has a relatively short half-life (approximately six hours), logistical reasons require local preparation of the drugs.
In a laminar airflow workbench (LAFW) with an L-block for protection, multidose vials of the various radiopharmaceuticals (also placed into tungsten vial shields) are compounded using specific amounts of Tc eluate and saline. Each drug kit has very particular compounding steps and procedures, which may include heating, venting, etc.
The pharmacist then hands the prepared multidose vials with corresponding prescription labels to technicians, who (in their own hoods) safely draw up unit doses into syringes with the help of a leaded glass syringe shield. Due to the lead/lead glass composition, these are relatively heavy, and require dexterity and practice to use properly.
The technician draws the volume indicated on the prescription label, and then verifies the activity by placing the syringe into a dose calibrator. The calibrator will indicate the current activity of the dose, as well as what it will read at the desired assay time indicated by the customer (i.e. 72 mCi now, and 30 mCi at 08:00).
Each unit dose (syringe) is placed into a lead-shielded “pig”, labeled, capped, and placed into a case to be shipped out to the hospital or clinic. When the dose arrives to the customer, a nuclear medicine technician/physician will verify the activity in their own calibrator, and administer the dose to the patient. After a set amount of time, the patient is scanned and the images are interpreted.
In addition, prior to doses leaving the pharmacy, quality control by chromatography is performed on each and every kit that is prepared to ensure the drug is sufficiently bound to the isotope, there are no impurities, etc. USP sets certain percentage requirements for each drug to pass QC, and each company may set even more stringent internal requirements (i.e. 95% purity or above to pass).
Radiopharmacology and the Common Procedures in Nuclear Medicine
Relatively speaking, there are really only a small number of radiopharmaceuticals and nuclear isotopes available. This permits nuclear pharmacists to become true experts in their practice. Approximately 80% of radiopharmacy is diagnostic; however, there are some fascinating and effective therapeutic drugs that we compound as well.
The following list does not include every radiopharmaceutical available, but will give you a good taste of what is available.
- Cardiology: this is the bread and butter of nuclear medicine. The major agents used are Thallium-201, Tc-99m Sestamibi (Cardiolite®) and Tc-99m Tetrofosmin (MyoviewTM). They are useful in myocardial perfusion imaging (i.e. comparing a ‘rest’ and ‘stress’ image to identify ischemia/infarction), avid infarct imaging (to detect damaged myocardial tissue post-MI) and cardiac function studies (to determine how well the heart is pumping via LVEF). These studies are a great tool for guiding a patient’s course of therapy; helping to determine whether they may need open heart surgery, catheterization, or strictly risk management with lipid control, and so on.
- Brain imaging: Tc-99m Exametazime (CeretecTM) and Tc-99m Bicisate (Neurolite®) are agents used to screen for tumors, detect metastases, detect intracranial injury, identify seizure foci, and even aid in determining legally defined ‘brain death’.
- Skeletal imaging: Tc-99m Medronate (MDP) and Tc-99m Oxidronate (HDP); are radiotracers with a bisphosphonate structure used to assess bone trauma (i.e. fracture imaging), distinguish osteomyelitis from cellulitis, evaluate bone cancer/multiple myeloma, paget’s disease, and so on.
- Treatment of pain due to bone metastasis: This is a good example of where nuclear medicine is used in treatment rather than strictly for diagnosis. Sr-89 Chloride (Metastron®) and Sm-153 Lexidronam (Quadramet®) can be far more effective than traditional therapy in helping cancer patients suffering from excruciating pain resulting from bone mets.
- Liver/Spleen imaging: Tc-99m Sulfur Colloid is essentially a radioactive particle that is phagocytized by the RES. It is used to image for hepatitis/cirrhosis, high LFT’s, liver tumor, trauma, abscesses, etc., where ‘cold spots’ (dark areas) in the image indicate an abnormality.
- Lymphoscintigraphy: small doses of filtered Tc-99m Sulfur Colloid are injected during surgery to locate lymphatic drainage patterns, guide oncological surgeons, and to identify the location of a sentinel node. The sentinel node (first node downstream from the tumor) can then be sent for biopsy to determine whether the cancer has metastasized>
- Hepatobiliary imaging: Tc-99m Mebrofenin (Choletec®) is used for gallbladder imaging to differentiate between acute (oftentimes caused by gallstones) and chronic cholecystitis. In acute cholecystitis, the gallbladder will light up in the scan, but does not for chronic disease.
- Renal imaging: Tc-99m Pentetate (DTPA) and Tc-99m Mertiatide (MAG-3) are two radiopharmaceuticals used for renal function imaging (i.e. quantifying GFR or tubular secretion), whereas Tc-99m Succimer (DMSA) is used to assess structure/anatomy of the kidney. These agents are useful in patients with renal obstruction, renal HTN, tumor, trauma, and so on.
- Pulmonary imaging: VQ scans are done to differentiate between a pulmonary embolism (lung clot) and chronic obstructive pulmonary disease (COPD). A perfusion test (using Tc-99m MAA) is generally done first. If the results are abnormal, the ventilation portion of the study (using radioactive Xe-133 gas or aerosolized Tc-99m DTPA) is performed. Normal ventilation will then indicate that the patient has a high probability of having a PE, whereas abnormal ventilation points to COPD.
- Thyroid imaging and treatment: since the thyroid gland naturally takes up iodine in order to produce thyroid hormones, administering radioactive iodine is a logical step in order to assess function (uptake) of the thyroid, as well as image or treat thyroid cancer. Thyroid uptake/function studies are performed by administering I-123 or I-131 NaI, which are useful in the diagnosis of hypo-/hyperthyroidism. Thyroid imaging can also be performed to assess ‘hot’ or ‘cold’ nodules on the thyroid; as well as whole body imaging, to look for metastatic tumors during follow-up of thyroid cancer. Thyroid therapy is a classic example of how nuclear medicine is used for treatment purposes. I-131 NaI is administered in higher activities to treat hyperthyroidism, as well as ablate the gland after surgery to mop up any remaining cells.
- Infection imaging: Ga-67, which is similar to iron, is passively localized to a site of infection and is an excellent choice for chronic infection imaging. Radiolabeled white blood cells can be an effective option in patients with an acute infection, inflammatory bowel disease, fever of unknown origin, osteomyelitis, soft tissue abscess, skin graft infection or diabetic foot ulcer. A hospital will send us a syringe containing a sample of the patient’s blood. In the pharmacy’s blood room (a completely segregated area from the remainder of the pharmacy), a needless procedure is used to extract the patient’s white blood cells. The leukocytes are then tagged with radioactive In-111 or Tc-99m Exametazime (CeretecTM). The patient’s own radio-labeled WBC’s are then sent back to the hospital where they are re-injected into the patient, and scanned to localize the site of infection.
- Monoclonal antibody imaging/therapy: this could quite possibly be the future for nuclear medicine, as there are so many possible applications for monoclonals. There are a only a handful of agents available now: In-111 Capromab Pendetide (ProstaScint®) to image prostate cancer, and In-111/Y-90 Ibritumomab Tiuxetan (ZevalinTM) or I-131 Tositumomab (Bexxar®); however many more are in production. ZevalinTM and Bexxar® are effective treatment options for patients with non-Hodgkin’s lymphoma.
- PET: is another fascinating area of nuclear medicine. F-18 FDG (“radioactive glucose”) is produced at a facility with a cyclotron, and is used to detect areas of the body undergoing high metabolism (i.e. epilepsy, cancer) relative to normal tissue. Since PET looks at the disease on a chemical level, you can identify the disease much sooner than when using other imaging modalities.
Authorized Nuclear Pharmacist (ANP) Training
As can be expected, the training necessary to become a nuclear pharmacist is very extensive. About 200 hours of didactic training, and 500 hours of hands-on experience are required to practice under a pharmacy’s RAM license.
There are a few ways to go about getting this and becoming an “ANP”: 1) Attend a pharmacy school that has a nuclear program, which is completed during the PharmD curriculum (i.e. Universities of Arkansas, Oklahoma, New Mexico, Tennessee ). Option 2) Once already a pharmacist, privately pay for training (i.e. through NEO). Option 3) Pursue a nuclear specialized residency (i.e. SUNY or Walter Reed) or Option 4) and this is probably what most people do; begin working for a nuclear pharmacy company. They will generally pay pharmacist salary while you do your training, and provide the training as well.
Typical Day at a Nuclear Pharmacy
Most pharmacies will typically have between 1 – 3 set “runs”. A typical day at my pharmacy begins at around midnight when the night pharmacist arrives; they will then begin to hit the generators and start compounding the first run. Technicians and drivers will begin to trickle in; doses are drawn (including FDG brought in from a cyclotron) and packed up. First run is out the door and on its way to customers between 04:00 – 05:00.
The pharmacist and technicians then have some down time to clean up, log all of the kits prepared during the run into the computer, grab a bite to eat, etc. Second run then starts at around 06:00; a second pharmacist arrives at around 07:00 as this is when the phones start to pick up with same day add-ons from the customers. Second run is out the door by 08:00. A third and fourth pharmacist arrive at 08:30. One of them will generally be designated to work on the bloods; another will help answer the phone, take orders, deal with customer service issues, etc.
Third run compounding (which is usually pretty light), begins at 10:00 and is out the door by 11:30. I-131 capsules will need to be compounded at some point during the day as well. Throughout the morning and afternoon, we’ll field phone calls ranging from STAT add-ons to clinical questions (i.e. pediatric dosing, altered biodistribution, questions about drug selection, and so on). The rest of the day is generally spent setting up for the next night: order entry, drawing any doses (i.e. Thallium, which has a long half-life) that can be drawn the day prior. Prescription labels are printed, double-checked and any products needed for the next day are ordered. So, as you can see, the daytime hours are generally spent getting ready for the following night.
The closing pharmacist locks up sometime around 17:00 and is on call for the remainder of the night.
Radiation safety and proper handling of all RAM is at the forefront of the training we receive. Employees are required to wear ring badges (to monitor extremity exposure) as well as a body badge at collar/thyroid level (to monitor whole body exposure). Rings are monitored weekly, and badges monthly, to assess each employee’s radiation exposure.
The US government has set limits (i.e. 5 REM/year for whole body exposure, 50 REM/year for extremities). In addition, companies will oftentimes have even stricter limits than these, and will assess each individual as necessary if their exposure approaches action levels. Most of the times, this will entail adjusting ones compounding techniques to ensure practice of “ALARA” principles. Each pharmacy will also have a “Radiation safety officer” (who may or may not be a pharmacist), and they are responsible for overall safety at the pharmacy: monitoring air concentrations, training personnel, and keeping employees under all federal/company radiation guidelines. Pregnant women can officially declare their pregnancy to the company as well, and will receive an additional fetal badge to be worn near the belly. She will have even stricter limitations to restrict the amount of radiation exposed to the child.
Advantages of Becoming a Nuclear Pharmacist
As mentioned earlier, this is a very specialized field and there is a general appreciation for the training/education a nuclear pharmacist has received. As you read in the description of a typical day in the pharmacy, (barring any problems), the pace is generally pretty relaxed with some lag time, especially at night. You become very close with your staff (technicians, drivers, administrators) and get to know your customers very well. You are treated as a professional and they value your input and services. After you’ve gotten enough hours under your belt, you’re also able to become board certified (BCNP) if you so desire; nuclear pharmacy was the first specialty area established by the BPS. There’s definitely opportunity for job growth through management. Nuclear pharmacy is a neat balance between clinical pharmacy, physics, chemistry, math, management, business/sales, customer service, current issues like the application of USP <797> across the industry; there is a little bit of everything for everyone.
Disadvantages of Becoming a Nuclear Pharmacist
The reality is, we deal with radiation and biohazardous material on a daily basis. We are however, provided with the training on how to deal with this properly, and it is in your own interest to do things by the book. Over-night hours are another stickler for some people. A fully staffed pharmacy though, will permit pharmacists to rotate their shifts. It may be possible that you will only have to work the opening shift one week out of every four to six.
Specializing in this field also requires us to keep up with “regular” pharmacy. Many times, hospital/retail pharmacists will not know what Cardiolite® is, but nuclear pharmacists rarely talk about the new factor Xa inhibitor anticoagulant either.
Many people ask me whether it’s difficult to find a job as a nuclear pharmacist. The answer is: no. It’s not hard to find “a” job; there will always be a demand for a well-trained specialist, however, unlike retail pharmacies, you’re not exactly going to find a nuclear pharmacy on every corner. As a result, it may take a little longer to find “the” opening you want, in the specific city/state you’re interested in.
Thank you for your interest in this topic; hopefully this article will spur further discussion of nuclear pharmacy and nuclear medicine on the SDN Forums. It’s a fascinating specialty practice that allows pharmacists to excel and provide valuable diagnostic and therapeutic options for our patients.
I encourage all students who are interested in the field to take an elective at your school if one’s offered, sign up for a nuclear rotation, or even contact a nearby pharmacy to shadow a pharmacist for a day.