How does a nuclear pharmacy get rid of its waste material?

It depends on the type of waste.

The restricted area of the pharmacy has a radioactive waste breakdown room that contains a few large lead-shielded barrels. Bags and ammo cans that return from the customers are brought in each day and broken down. Syringes are segregated into different barrels according to the isotope...short-lived ones (i.e. Tc-99m) in one barrel, longer-lived ones (i.e. Ga-67, In-111, Tl-201) in another, etc.

Once the barrel is full it's sealed and stored in the pharmacy for at least ten half-lives...and then once it has reached background levels (which you determine by using a survey meter), it can be disposed as "regulated medical waste". This is biohazardous material (since the needles have been injected into patients) that we send off to Stericycle.

Other non-biohazardous trash that we produce in the pharmacy during compounding (i.e. gloves, pads) can be thrown in the regular trash as long as it isn't hot.

The generators which we use to obtain Tc-99m are good for 14 days. Lantheus generators are sent to us with lead shielding, and once we buy them, they're ours (i.e. we have to break them down, and store the Mo-99 cores for a few years). Covidien generators are sent out with depleted Uranium shielding (and therefore can ride in passenger aircraft). They can't be broken down, and Covidien provides a return box to send the generator back to them.

The pharmacy produces tons and tons of lead waste too from all the material we receive...which we sell by the pound each month to be recycled.

Another big thing...all radioactive symbols/signs on packaging must be obliterated prior to throwing it out in the trash. We can get audited/fined big time if someone finds that in a dumpster.

Uses Of Radiopharmacology

Radiopharmacology
This is what really drew me in to the field. Relatively speaking, there are really only a small number of radiopharmaceuticals and nuclear isotopes used, and this allows us to become experts on a good majority of them. 80% of radiopharmacy is diagnostic; however, there are some fascinating and effective therapeutic drugs that we compound as well. Now, I’m not going to go into each and every drug, but these are the big ones, and it’ll give you a good taste for what’s out there.

• Cardiology: this is the bread and butter of nuke med and the major agents used are Thallium-201, Tc-99m Sestamibi (Cardiolite®) and Tc-99m Tetrofosmin (Myoview™). They’re 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...determining whether they may need open heart surgery, cath, or strictly risk management with lipid control, etc.

Brain imaging: Exametazime (Ceretec™), Bicisate (Neurolite®); these agents can be used to screen for tumors, detect metastases, detect intracranial injury, determine legally defined ‘brain death’, identify seizure foci, etc.

• Skeletal imaging: Tc-99m Medronate (MDP) and Tc-99m Oxidronate (HDP); are radiotracers with a bisphosphonate structure that you’re all familiar with. These can be used to assess trauma (i.e. fracture imaging), distinguishing osteomyelitis vs cellulitis, evaluate bone cancer/multiple myeloma, paget’s disease, etc.

Treatment of bone metastasis: here’s a good example of where nuke medicine is used for 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 from bone mets.

Liver/Spleen imaging: Tc-99m Sulfur Colloid; used to image for hepatitis/cirrhosis, high LFT’s, liver tumor, trauma, abscesses, etc.; where ‘cold spots’ (dark areas) will indicate an abnormality.

Lymphoscintigraphy: small doses of 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 metastasic status.

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 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 are useful in patients with renal obstruction, renal HTN, tumor, trauma, etc.

Pulmonary imaging: VQ scans are done to differentiate between a pulmonary embolism (lung clot) and COPD. A perfusion test (using Tc-99m MAA) is 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 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, helping to determine 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 (treatment of choice), 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 the drug of choice for chronic infection imaging. Radiolabeled white blood cells can be used to image acute infection, inflammatory bowel disease, fever of unknown origin, osteomyelitis, soft tissue abscess, skin graft infection, diabetic foot ulcer, etc. A hospital will send us a syringe containing 60 cc of the patient’s blood. In our blood room (a completely segregated area from the remainder of the pharmacy), we use a completely needless procedure, involving centrifuging the sample, to extract the patient’s white blood cells. The WBC’s are then tagged with radioactive In-111 or Tc-99m Exametazime (Ceretec™). The patient’s own radio-labeled WBC’s are then sent back to the hospital, within 5 hours they are re-injected into the patient, and scanned to localize the site of infection. On a busy day, we’ll do anywhere up to 12 - 15 bloods.

• 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 (Zevalin™) or I-131 Tositumomab (Bexxar®); however many more are in production. Zevalin™ and Bexxar® are effective treatment options for patients with non-Hodgkin’s lymphoma.
  

• PET: this is actually another fascinating area of nuclear medicine that I could go into a lot of detail, but to keep it simple…FDG (think radioactive glucose), which is produced at a facility with a cyclotron, is used to detect areas of the body undergoing high metabolism (think 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.

 

• Adjunctive agents: there are a handful of non-radioactive meds that we dispense a lot of too, and they include pharmacological stress agents which are used when a patient isn’t able to exercise prior to a ‘stress’ portion of a myocardial study (i.e. dipyridamole, adenosine, regadenoson, dobutamine); aminophylline (an antidote used to reverse stress agents); and sincalide (to cause the gallbladder to empty for hepatobiliary imaging).

Well, I’ve been meaning to do this for quite a while since I’m constantly asked and PM’d with questions regarding nuclear pharmacy. It’s a very specialized niche in our field...and unfortunately, many healthcare professionals (and even other pharmacists) have a very vague understanding of what we do.

So, here it goes...a very thorough description (sorry!) of the world that is nookyoolar pharmacy, and what I go through on a daily basis.

To give you a quick overview of the industry’s current standing: nuclear pharmacies are generally either institutional (and cater to a single medical center), or commercial. Centralized commercial pharmacies are contracted by hospitals/clinics to provide radiopharmaceuticals, and there really are only a few major players out there: GE (FKA Amersham), Triad (FKA Tyco, Mallinckrodt, or Covidien), and Cardinal Health (which bought out Syncor, among others)...and smaller independents.

Moly Generators and Compounding Radiopharmaceuticals

Unlike CT/MRI, nuclear imaging is great at assessing function, as opposed to just structure or anatomy. Technetium (Tc-99m) is by far the predominant isotope used...it’s an ideal diagnostic tracer and we use it to compound the vast majority of our radiopharmaceuticals. I won’t go into the gory details, but Tc is obtained by a eluting a generator: a vial of saline is placed at the entry point 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 Tc-99m eluate is produced (think radioactive saline). Depending on the amount of activity needed for the run (and the number of doses the pharmacy puts out), several generators are hit throughout the course of the day. This Tc-99m elution is then used to compound most kits.

In a 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 particular compounding steps (i.e. some require heating, venting, etc.).

The compounder/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. These are actually a little heavy and require a lot of dexterity/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. 82 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 dose in their own calibrator, and administer the dose to the patient.

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 QC to pass for each drug, and each pharmacy may also set even more stringent internal requirements (i.e. 95% purity or above to pass).

What is nuclear pharmacy?

Nuclear pharmacy is a specialty area of pharmacy practice dedicated to the compounding and dispensing of radioactive materials for use in nuclear medicine procedures.  A specialty area of pharmacy practice is one that requires a concentration of knowledge in a once specific area.  The development of nuclear pharmacy as a specialty area followed the development of nuclear medicine as a recognized specialty by the American Medical Association in the early 1970's.

Prior to discussing the field of nuclear pharmacy, it is important to understand some background regarding radioactivity and how it is used in patients.  Most people hear the word radiation, and immediately have an image of danger or injury.  However, most people do not realize that there is radiation in everyone's lives in many different forms.  Electromagnetic radiation is emitted from the sun, from signals sent from radio and TV stations, from radar used to track airplanes, and even visible light.  In this particular field, we are interested in a type of radiation termed radionuclides.  A radionuclide is an atom that has an unstable nucleus.  Recalling chemistry, the nucleus of an atom consists of protons and neutrons.  If a nucleus, for whatever reason, has an excess of either one of these constituents, it will try to "get rid of" the excess component and return to a stable state.  By doing so, the atom is said to give off this energy in the form of radiation.  There are quite a few naturally occurring radionuclides.  Any nuclide with an atomic number greater than 83 is radioactive.  An atom's atomic number is simply the total number of protons found in the nucleus.  There are also many naturally occurring radionuclides with lower atomic numbers.

While some radionuclides occur naturally in the environment, there is another class of "man-made" or artificial radionuclides.  Artificial radionuclides are generally produced in a cyclotron or some other particle accelerator, in which we bombard a stable nucleus with specific particles (neutrons, protons, electrons or some combination of these).  By doing so, we make the nucleus of our starting material unstable, and this nucleus will then try to become stable by emitting radioactivity.

An unstable nucleus can give off its energy in a variety of ways.  The type of emission that is given off will determine whether or not the radionuclide will be useful for imaging or treating a patient.  The radiologic specialty of nuclear medicine uses small quantities of radioactive materials with a known type of emission.  By "tagging" the radioactive source to some compound that is known to localize in a specific area of the body, the compound will carry the radioactive material to the desired site.  By using a specific detection device called a gamma camera, it is possible to detect the emissions given off by the radioactive material and create images of the relative distribution of the radioactive source in the body.

As nuclear medicine procedures became more widely used, the need for someone to prepare the labeled products for administration to the patients became more evident.  While many large hospitals were able to use pharmacists with training in the handling of radioactive material, smaller hospitals were unable to utilize nuclear medicine procedures because they did not have the staff to prepare the necessary doses in a cost effective manner.  As a result, in the early 1970's, the concept of centralized nuclear pharmacies was born.  When developed, the centralized nuclear pharmacy served as the "drugstore" for the nuclear medicine department.  When a particular radioactive material was needed, a trained nuclear pharmacist was available to prepare the product and dispense it to the end user.  When you look at a nuclear pharmacy, its operation is not much different than that of a traditional pharmacy - a "prescription" for a particular product is presented, and the nuclear pharmacist must prepare and dispense that "prescription".  Where a traditional pharmacist will dispense doses in milligram weight units, a nuclear pharmacist will dispense in millicurie activity units.  Where a traditional pharmacist dispenses tablets and capsules, a nuclear pharmacist dispenses the radioactive material in liquid or capsule form.  Where a traditional pharmacist will generally dispense the prescription to the patient, the nuclear pharmacist will dispense to a hospital or clinic nuclear medicine department where the dose will be administered to the patient.  In general however, the 2 branches of pharmacy are strikingly similar.

There are some inherent differences in nuclear pharmacy practice, which ultimately warranted its designation as a specialty pharmacy practice.  There are certain areas of practice unique to nuclear pharmacy, as well as a separate class of drugs that are used.  The most striking would be the fact that radioactive material is being used to create the final products.  While the quantity used is small, there are still certain precautions that must be taken into account when handling on a day to day basis.  The nuclear pharmacist is extensively trained in radiation safety and other aspects specific to the compounding and preparation of radioactive materials.

In most nuclear pharmacies, the nuclear pharmacist is responsible for obtaining the desired radioactive material, either from a manufacturer, or from an in house generator system.    The most commonly used isotope in nuclear medicine is Technetium-99m that is readily and continuously available from a generator system.  The generator forms the radionuclide that is retained on an internal column until the generator is "milked".  When "milking" the generator, sodium chloride is passed over the column, which removes the radioactive material.  The eluate is then collected in a shielded evacuated vial.  After performing quality assurance tests on the eluate, it can be used in the preparation of the final radiopharmaceutical products.

In order to provide protection while handling radioactive material, most compounding is done behind leaded glass shielding and using leaded glass syringe shields and lead containers to hold the radioactive material.  Lead is an excellent shielding material that serves to protect the nuclear pharmacist from the radioactive emissions from our products.  Nuclear pharmacists work with large quantities of radioactive material on a day-to-day basis, but by using simple techniques, the amount of radiation exposure to the nuclear pharmacist is very low.

With over 100 different nuclear medicine procedures performed today, there are many different products that can be used.  Most radiopharmaceuticals are available as "kit" formulations.  All materials necessary for preparation are available in the nonradioactive kit with the exception of the radioactive isotope.  When the radioactive isotope is added to the kit, the chemical reactions required for binding the isotope occur within the vial.  In most cases, when the tagging reaction is complete, the final product will be ready for quality control verification and unit dose dispensing.

Since nuclear pharmacy practice involves the on-site compounding of most of the products being dispensed, each product that is compounded in the nuclear pharmacy must be tested prior to dispensing any individual doses.  Simple instant thin layer chromatography tests quickly and accurately provide information on the radiochemical composition of the kit that was prepared.  When the radiochemical purity of the compounded product is verified, it can be dispensed for use in patients.

Most radiopharmaceutical doses are delivered to the end user in unit dose syringe form.  This makes it easy for the nuclear medicine department to order the necessary doses, keep track of deliveries, administer the product ot the patient and minimize radioactive waste.  In a nuclear pharmacy, unit doses must be drawn from the prepared radiopharmaceutical kit for delivery to the nuclear medicine department.  Again, leaded glass syringe shields and other tools help decrease the radiation exposure to the nuclear pharmacist. 

In addition to preparing and dispensing the radioactive products, nuclear pharmacists are available to provide drug information to other health professionals, to aid the nuclear medicine staff in the selection of products, and to assist in the interpretation of unusual studies.  Nuclear pharmacists receive extensive training on the various radiopharmaceuticals that are used, as well as training on the safe handling of radioactive materials and the procedures that will minimize radiation exposure to themselves and to others.  There are very few schools of pharmacy that have any courses in nuclear pharmacy - Purdue University is unique in that it has several undergraduate courses available to students enrolled in the school of pharmacy, as well as a continuing education certificate program which allows licensed pharmacists who have had no exposure to nuclear pharmacy the opportunity to receive the necessary training to become a nuclear pharmacist.

Nuclear pharmacists serve as vital links in the provision of nuclear medicine services.  By working closely with the nuclear medicine staff, nuclear pharmacists can contribute a tremendous amount to the provision of care for the patients who are undergoing nuclear medicine procedures.  While similar to traditional pharmacy, nuclear pharmacy is also in many ways unique, and can be a challenging and rewarding career choice for pharmacists.