Nuclear Pharmacy

Nuclear Pharmacy

By Dr. Fatima Balquis

Nuclear Pharmacy Overview

• Nuclear pharmacy is a specialized area of pharmacy practice.

• Focuses on the compounding and dispensing of radioactive materials for nuclear medicine procedures.

• Radiopharmaceuticals are medicinal formulations that contain radioisotopes.

• Used in major clinical areas for diagnosis and/or therapy.

• Nuclear pharmacy, also referred to as radio pharmacy, deals with the preparation of radioactive materials intended for patient administration that diagnose and treat specific diseases in nuclear medicine.

Background Regarding Radioactivity

• Radiation is typically associated with danger or injury.

• Electromagnetic radiation is emitted from various sources, including:

  • The sun

  • Radio and TV signals

  • Radar for airplane tracking

  • Visible light

• In nuclear pharmacy, the type of radiation of interest is radionuclides.

• A radionuclide is defined as an atom with an unstable nucleus.

Recalling Chemistry

Atomic Structure

• The nucleus of an atom contains:

  • Protons (P)

  • Neutrons (N)

• Atomic Number (Z): Number of protons, also equal to the number of electrons.

• Mass Number (A): Total number of protons and neutrons.

• The number of neutrons can be calculated as:
  $N = A - Z$

• The nucleus with its protons and neutrons is termed a nuclide.

Isotopes

• Isotopes are nuclides of the same chemical element with:

  • Same number of protons

  • Different number of neutrons

• Example isotopes of Hydrogen:

  • $^1H_1$ (Hydrogen)

  • $^2H_1$ (Deuterium)

  • $^3H_1$ (Tritium)

Isobars and Isotones

• Isobars: Nuclides of different elements with the same mass number.

  • Example: $^3H<em>1$ (Tritium) and $^3He</em>2$

• Isotones: Nuclides of different elements with the same number of neutrons.

  • Example: $^3H<em>1$ and $^4He</em>2$

Stability and Radioactivity

• If a nucleus has an excess of protons or neutrons, it will attempt to return to stability by emitting energy as radiation.

• Any nuclide with an atomic number greater than 83 is considered radioactive.

• Atomic number is defined as the total number of protons in the nucleus.

Natural vs Artificial Radionuclides

• Some radionuclides occur naturally, while others are man-made or artificial radionuclides.

• Artificial radionuclides are generated in a cyclotron or particle accelerator by bombarding stable nuclei with particles (neutrons, protons, or electrons) to render the nucleus unstable.

Emission Types

• An unstable nucleus can emit energy in various forms.

• The type of emission affects the radionuclide's utility in imaging or treatment:

  • Nuclear medicine utilizes small, known quantities of radioactive materials.

  • By tagging radioactive sources to biologically active compounds, they can target specific body areas.

  • Using a gamma camera allows for emission detection and subsequent imaging of radioactive distribution in the body.

Comparison with Other Imaging Techniques

• Nuclear Medicine vs. Other Diagnostic Procedures:

  • Unlike X-rays, CT scans, ultrasounds, and MRIs, nuclear medicine detects radiation emitted from within a patient's body.

  • Other methods involve external radiation exposure.

• Nuclear medicine assesses organ function rather than solely anatomical structure.

Radiopharmaceuticals Overview

• A radiopharmaceutical:

  • Radioactive compound used in diagnosis and therapy.

  • 95% of applications are diagnostic; 5% therapeutic, with minimal pharmacologic effect.

  • Must be sterile, pyrogen-free, and pass quality control.

Components of Radiopharmaceuticals

1. Pharmaceutical: Selected based on its localization in an organ or participation in its physiological function.

2. Radionuclide: Is tagged to the pharmaceutical; radiation is then detected post-administration.

• The pharmaceutical must be safe and nontoxic with minimal radiation dose.

Ideal Characteristics of Radiopharmaceuticals

1. Easy Availability:

   • Should be cost-effective, easily produced, and available at nuclear medicine facilities.

2. Short Effective Half-Life:

   • Reflects both physical decay and biological elimination.

3. Particle Emission:

   • Alpha and beta emitters should not be labels in diagnostic applications due to excessive tissue damage; they are useful in therapy.

4. High Target to Non-target Activity Ratio:

   • Must localize preferentially in the target organ for effective imaging.

Radioactivity Processes

• Radioactivity: The process where unstable nuclei emit energy as particles, electromagnetic waves, or both.

• Radioisotopes: Radionuclides undergoing such transformations.

• Radiolysis: The decomposition of labeled compounds due to radiation from incorporated radionuclides, influenced by specific activity and half-life.

Types of Emissions

• Alpha Particles ($^4_2α$): Consist of 2 protons and 2 neutrons, penetrating air to 5 cm and tissues less than 0.1 mm.

• Beta Particles:

  • Can be positrons ($^0<em>1β^+$) or negatrons ($^0</em>1β^-$) with reach of 3 m in air and approximately 1 mm in tissues.

• Gamma Radiation ($γ$): Electromagnetic waves, high penetration (up to 1 km in air, 25 cm in tissues).

List of Radiopharmaceuticals

1. Carbon-11:

   • Chemical Symbol: $^{11}C$

   • Half-life: 20.334 minutes

   • Used for PET imaging of prostate cancer recurrence.

2. Fluorine-18:

   • Chemical Symbol: $^{18}F$

   • Several chemical forms such as Florbetapir with a half-life of 109.771 minutes, effective for assessing prostate cancer recurrence, abnormal glucose metabolism, and osseous alterations.

3. Gallium-67:

   • Effective in diagnosing Hodgkin’s disease and lymphoma through its presence in gallium citrate.

   • Half-life: 3.26 days

4. Indium-111:

   • Chemical forms for prostate cancer diagnostics with a half-life of 2.80 days.

5. Iodine-123:

   • Used in detecting pheochromocytoma and neuroblastoma with a half-life of 13.22 hours.

6. Molybdenum-99:

   • Half-life: 2.7489 days, generates Tc-99m sodium pertechnetate.

Additional Radiopharmaceuticals

• Nitrogen-13, Radium-223, Rubidium-82, Samarium-153, Strontium-89, Technetium-99m, Thallium-201, Xenon-133, Yttrium-90, Chromium-51

Units of Radioactivity

Activity Units

1. Curie (Ci):

   • Decay rate: $1 ext{ Ci} = 3.7 imes 10^{10} ext{ dps}$

2. Millicurie (mCi):

   • $1 ext{ mCi} = 3.7 imes 10^7 ext{ dps}$

3. Microcurie (µCi):

   • $1 ext{ µCi} = 3.7 imes 10^4 ext{ dps}$

Dose Units

1. Exposure Dose: Measured in Röntgen (R), the quantity that produces a unit charge in air.

2. Absorbed Dose: Measured in Radiation Absorbed Dose (rad), where 1 R approximately equals 1 rad.

Advantages of Nuclear Medicine

• Useful for diagnosis and treatment, particularly for cancers.

• Can treat multiple disease sites effectively.

• Provides direct tumor treatment, notably for bone metastasis.

• Quick pain relief for some patients from a single dose.

• Procedures are child-friendly, cost-effective, and painless with no side effects.

Disadvantages of Nuclear Medicine

• Potential allergic reactions.

• Radiation risks exist.

• May cause myelosuppression, particularly following prior chemotherapy.

• Multiple fractions can lead to discomfort.

• Tests not advisable for pregnant women due to heightened fetal sensitivity to radiation.

Procurement and Compounding

Procurement

• Involves specifying product requirements, ordering, receiving, and inventory management.

• Nuclear pharmacists typically order from manufacturers directly, often via overnight delivery.

• Safe storage requires appropriate radiation shielding as well as standard environmental controls.

Compounding

• Requires valid prescriptions and appropriate components and conditions.

• Includes reconstituting reagent kits and strict aseptic techniques.

• A freeze-dried kit is reconstituted with sterile sodium pertechnetate using aseptic practices.

• Final doses may require diluents for desired radioactivity levels.

Quality Assurance

• Must meet standards for radionuclide concentration, radiochemical purity, and sterility.

• Ensures absence of contaminants and particle size where applicable.

Dispensing and Distribution

• Dosage levels must consider patient specifics including history and physical conditions.

• Must adhere to pharmaceutical laws and regulations during distribution.

• Policies should ensure drugs are dispensed accurately and timely.

• Ensures compliance with regulations regarding packaging, labeling, and transportation, including DOT requirements.

Radiation Safety and Patient Information

Allergy Considerations

• Patients receiving specific albumin-based tests must report any prior allergic reactions to human serum albumin.

Pregnancy Precautions

• Radiopharmaceuticals are typically not recommended during pregnancy due to fetal exposure risks, particularly with iodine-based products.

Pediatric Considerations

• Generally, diagnostic radiation doses used for children are minimal and considered safe.

Side Effects

• Side effects from small doses are rare but primarily based on allergic reactions.

General Safety Information

• Radiopharmaceuticals are generally considered safe when managed correctly with proper precautions.

Post-Procedure Care

• Patients are advised to drink fluids post-procedure to facilitate flushing out residual radioactivity.

Calculation Example

• For $^{111}In$, with a physical half-life of 67 hr and a biological half-life of 1.5 hr, the effective half-life (Te) is calculated as follows:
  $T<em>e = rac{T</em>p imes T<em>b}{T</em>p + T_b} = rac{67 imes 1.5}{67 + 1.5} = rac{100.5}{68.5} = 1.47 ext{ hr}$

Principles of Radiation Protection

• Handling of radiopharmaceuticals must comply with regulations for safety and protection.

Core Principles

1. Justification: All procedures with radioactive materials must be justified.

2. Optimization: Minimize radiation exposure (ALARA - As Low As Reasonably Achievable).

3. Limitation: Maintain legally established radiation dose limits for personnel.

Exposure Reduction Strategies

• Time: Limit exposure duration to decrease dose.

• Distance: Increase distance to reduce radiation dose.

• Shielding: Employ shielding materials, especially against gamma radiation using heavy concrete or lead.

Formulation and Production of Radiopharmaceuticals

• Safety considerations must be prioritized when designing a radiopharmaceutical.

• Carrier molecules must ensure safe delivery of radioactivity to the target organ.

• Careful assessment of chemical properties is key in developing effective radio-labeled compounds.

Good Radiopharmaceutical Practice (GRP)

• Ensures operator and environmental safety from radioactive contamination.

Radio Pharmacy Design (Location)

General Guidelines

• Must be strategically located in a nuclear medicine/radiology department, preferably at the end.

• Minimize radiation concerns through proper location and shielding techniques.

• Delivery access must be convenient for shipments, especially for external units.

Layout Considerations

• Restricted access is necessary for safety and security in manufacturing areas.

• Floors must be suitable for cleanliness, and equipment must be tailored for radiopharmaceutical production.

Personnel Monitoring and Waste Management

Monitoring

• Radiation workers must be equipped with personal dosimeters to track exposure levels.

Waste Management

• Segregation of radioactive from non-radioactive waste is crucial.

• Secure storage and periodic monitoring of all radioactive waste are mandated.

• Waste disposal methods include decay in storage, sewer release, or transfer to authorized recipients.

Dose Calibration Quality Assurance

• Regular verification of dose calibrator accuracy is essential.

• Routine checks must be documented for compliance and quality control.

Blood Labeling Techniques

• Different elements of blood can be labeled with various radionuclides for clinical application.

Applications

• In vitro Spleen Imaging: Utilizes $^{99m}Tc$-pertechnetate for denatured red cells.

• In vivo/in vitro Measurements: Red cell volume can be assessed with $^{99m}Tc$-pertechnetate and $^{51}Cr$-chromate.

• In vitro Red Cell Survival: Investigated with $^{51}Cr$-chromate.

• Infection Detection: White blood cells labeled with $^{111}In$-tropolone for inflammation studies.

• Abnormal Platelet Studies: Labeled platelets with $^{111}In$-oxine and $^{99m}Tc$-HMPAO for assessing deposition abnormalities.