CLRS 461 Radiopharmaceuticals:  Preparation and Quality Control Fall 2023

Mark Crosthwaite
Office phone 828-9104
Cell phone 855-7406
Tuesdays and Thursdays - 10:15 AM to 11:10 AM
Location: Room 1000
Office Hours: M-1300 to 1500, W-1300 to 1600, and R-1300 to 1600

Course Description
CLRS 461. Radiopharmaceutical: Preparation and Quality Control
Semester course; 2 lecture hours. 2 credits. Prerequisites: CLRS 319, CLRS 322 and CLRZ 322, all with a minimum grade of C. Provides the technical knowledge necessary for the preparation and quality control of radiopharmaceutical agents for in-vivo and in-vitro nuclear medicine studies.

Textbooks

  1. Christian, et al Nuclear Medicine And PET/CT Technology and Techniques, 8th edition St. Louis, 2017 Mosby/Elsevier
    You are required to read the following
    1. Chapters 3 and 4 (pages 56 to 107)
    2. Appendix C
  2. Saha, G.B. Fundamentals of Nuclear Pharmacy, 7th edition, New York, 2018, Springer (recommended). Amazon link
  3. Use VCU Libraries to find and access library resources, spaces, technology and services that support and enhance all learning opportunities at the university - link https://www.library.vcu.edu/

Grading Scale

93-100.............A
85-92...............B
84-77...............C*
60-76...............D
68 and below...F

* Minimum passing grade

Method of Evaluation Exam Date Percent
Exam I: Radionuclide Production
9/12
15%
Exam II: Radiophamaceutical and Dose Calculations
10/5
20%
Exam III: Radiopharmaceutical Chemistry and TLC
11/21
20%
Final Exam: Comprehensive
TBA
25%
Assignment
12/8
15%
Homework/Kahoot
Unannounced
5%

Issues related to this course

  1. USP - Regulations <797> and <825> requires all radiopharmaceutical compounding to be done in a "clean room."  This has forced MCV to stop their in-house radiopharmacy program. Because of this, radioactive compounding will be taught in conjunction with this course, CLRZ 461

Exams and Assignment Policy

  1. Exams will encompass information discussed during lectures, handouts given in class, and homework/reading assignment.  Failure to take an exam on a scheduled exam day will automatically cause a 5% deduction from the exam grade.  Make-up must be scheduled and completed ASAP, so that the entire class has the opportunity to review their results.  The only exception given to this policy will be if the student has made other arrangements with the instructor.
  2. There will be unannounced quizzes or Kahoots throughout the semester that may occur at the beginning of class. Make-up quizzes will not be given.  A quiz will be completed within the first 5 minutes of class. Should you arrive late and the 5 minute time period is not over you use whatever time that remains to complete the quiz. You will be allowed to drop your lowest quiz grades. If it is a Kahoot, all that is required is your participation to receive credit. Attendance is required and highly recommended that you show up for class. Failure to show up means that you may miss a quiz or a Kahoot which will translate to zero points.
  3. The Department Chair establishes policies and schedules for the CLRS final exams. The Department Chair must approve any changes regarding scheduling the course final exam. A penalty may be imposed for missing a scheduled final exam.
  4. Any assignment or homework given in class must be completed in a time designated by the instructor.  Late assignments will not be accepted.
  5. This is one of the professional courses in which means that the lowest passing grade is “C.”

Attendance Policy
Attendance is mandatory for all classes. See quizzes

Course Requirements

  1. Regular class attendance.  If absent, it is your responsibility to get handouts, notes, and any other information presented
  2. Reading assignments
  3. Complete all exams
  4. Final exam
  5. Perform all assigned homework/ projects/ assignments

University Policies The updated statements for syllabi and blackboard pages are available at https://provost.vcu.edu/academic-affairs/operations/syllabus-statements/

VCU Honor System
Students are responsible for being familiar with and adhering to the VCU Honor Code and student conduct policy  as outlined in the current VCU Resource Guide, available at: https://conduct.students.vcu.edu/vcu-honor-system/

Religious Holiday
If you have a religious that requires you to miss call you must tell the instructor, no later than September 1st as per University policy. See Academic Calendar

ADA Policy:
Section 504 of the Rehabilitation Act of 1973 and the Americans with Disabilities Act of 1990 require VCU to provide academic adjustments or accommodations for students with documented disabilities.  Students seeking academic adjustments or accommodations must self-identify with the Coordinator of Services for Students with Disabilities on the appropriate campus.  After meeting with the Coordinator, students are encouraged to meet with instructors to discuss their needs and, if applicable, any laboratory safety concerns related to their disabilities

Please refer to the VCU ADA policy in the Division for Academic Success, available at https://das.vcu.edu/

Policy Regarding Calculators
The Department of Radiation Sciences will only allow use of non-programmable (non-graphing) calculators.  Stud ents will not be allowed to use programmable (graphing) calculators during any type of examination.  In addition, students will not be allowed to share calculators during any examination

Policies Regarding the Academic Calendar and Course Schedule1, 20

How to Prepared for Emergencies at VCU

  1. Sign up to receive VCU text messaging alerts (http://www.vcu.edu/alert/notify).  Keep your information up-to-date
  2. Know the safe evacuation route from each of your classrooms. Emergency evacuation routes are posted in on-campus classrooms
  3. Listen for and follow instructions from VCU or other designated authorities
  4. Know where to go for additional emergency information (http://www.vcu.edu/alert)
  5. Know the emergency phone number for the VCU Police (828-1234)
  6. Report suspicious activities and objects

Students should visit syllabus statement by the Office of the Provost for additional syllabus information: https://provost.vcu.edu/faculty/faculty-resources/syllabus The full university syllabus statement includes information on safety, registration, the VCU Honor Code, student conduct, withdrawal and more

Course Objectives

  1. Identify the parts of a nuclear reactor and apply the fission process of 235U within the reactor.
  2. Understand the "short hand" equation in a nuclear reaction.
  3. Define neutron activation/capture and transmutation.
  4. Identify the need to produce carrier free radioisotopes and complications associated with radio-compounds that might not be carrier free. 
  5. Discuss the components in a linear accelerator and cyclotron.
  6. Identify the role of the different components found in a 99Mo/99mTc generator. 
  7. Calculate the build up of 99mTc in a 99Mo/99mTc generator. 
  8. Calculate Molly breakthrough and know the legal limits. 
  9. Apply Al+3 breakthrough in a Colormetric test. 
  10. Understand the basic components of the liquid 99Mo/99mTc generator.
  11. Measure and calculate your Molly breakthrough (μCi/mCi).
  12. Calculate the amount of activity in the elution vial and determine its concentration
  13. Understand the basic components 82Sr/82Rb generator.
  14. Simulate compounding of kit and unit dose calculations
    1. Adult
    2. Pediatric
    3. Assure that there is enough activity in the compounded radiotracer to dose ALL your patients
  15. Apply the decay formula whenever appropriate
  16. Identity kit expiration and appropriate disposal
  17. What is the difference between electrophilic and nucleophilic?
  18. Evaluation 99mTc chemistry to include:
    1. Valence states
    2. Reduction and re-oxidation
    3. Identify impurities in an aqueous solution
    4. Identify by-products of stannous ion
    5. Determine acceptable ratios of 99mTc to Sn
    6. Define and give an example of ligand exchange
    7. Define a bifunctional chelator
    8. Define and give an example of transchelation
    9. Identify the three methods of labeling RBCs
  19. Apply components necessary to determine radiopharmaceutical purity (TLC)
    1. Know where the impurities are located on a TLC strip - MDP, SC, and MAA
    2. Calculate radiopharmaceutical purity
    3. Determine particle size acceptance
    4. Identify and calculate 99Mo breakthrough
    5. Identify other methods for testing radiopharmaceutical purity
  20. Determine methods to assess radiopharmaceutical
  21. Discuss rules and regulations with FDA, NRC, DOT as it relates to radiopharmacy
  22. Discuss regulations associated with USP <725> and <825>

Lecture Outline and Reading Assignments
  1. (8/22 - 8/30) Radioisotope Production and Generator Systems – Saha 4 - 5
    1. Fission reactors
    2. Particle Accelerators
    3. Generators
      1. Architecture
      2. Elution
      3. Parent-daughter equilibrium
      4. Quality Control
      5. Dose Calculations
      6. Simulated compounding and unit dose calculations (considerable time will be given in this area)
    4. Toxicity - chemically is this a problem?
  2. 9/5 - 9/21) Radiopharmaceuticals – Saha 6
    1. Commercial preparations
    2. Methods of radiolabeling
    3. Kit Preparations

    Exam I - 9/26

  3. (9/28) Radiopharmaceutical Localization
    1. Mechanisms
      1. Compartmentalization
      2. Diffusion
      3. Active transport
      4. Metabolic incorporation
      5. Phagocytosis
      6. Cell sequestration
      7. Capillary blockade
    2. Kinetics
      1. Single compartment
      2. Multiple compartments
  4. (10/3) Designing a radiopharmaceutical Saha 6.1 and 6.2
  5. (10/5) Methods of Radiolabeling - Saha 6
  6. (10/10) 99mTc chemistry Saha 6.6
  7. (10/12 - 10/17) Biological Considerations – Saha 8
    1. Hydrogens and testing
    2. Biological controls
    3. Sterility and testing
    4. Radiation effects
  8. (10/24 ) Radiopharmaceutical Quality Control – Saha 8
    1. Radionuclide prity
    2. Radiochemical purity
    3. Particle sizing
  9. (10/26 - 11/2) Chromatography and Separation Techniques – Saha 8
    1. Partition chromatography
    2. Absorption
    3. Ion Exchange
    4. Electrophoresis
    5. Dialysis

    Exam II 11/3

  10. (11/7 - 11/19) Radiopharmaceuticals grouped by organ/system – Saha 13
    1. Bone agents
    2. Inflammatory agents21ulmonary agents
    3. Cardiac agents
    4. Tagged RBCs
    5. Renal Agents
    6. Gastrointestinal agents
    7. Endocrine agents
    8. Monoclonal antibodies
    9. Peptides
    10. PET Agents
  11. (11/7 to 11/21) For each diagnostic radiopharmaceutical the following topics are covered - Saha 7
    1. Preparation of compound
    2. Dose calibration
    3. Chemistry
    4. Physiology
    5. Emission characteristics
    6. Patient dose
    7. Half-life
      1. Biologic
      2. Physical
      3. Effective
  12. (11/7 -11/21) Therapy radiopharmaceuticals – Saha 15
    1. 131I
    2. 32P
    3. 89Sr
    4. 153Sm
    5. 90Y
    6. 177Lu

    Exam III - 11/17

    Fall Break - Week of 11/22

  13. (11/28 - 11/30) Regulatory Compliance – Saha 11
    1. Nuclear Regulatory Commission (NRC)
    2. Agreement states
    3. Information labeling, Inventory, Record Keeping
    4. Food and Drug Administration (FDA)
      1. Investigation New Drug (IND)
      2. New Drug Application
    5. Department of Transportation (DOT)
  14. (12/5)The effects of regulation <797> and <825> - Saha Chapter 9
  15. PET radiopharmaceuticals may be covered depending on the time remaining in the course. PET is covered in detail, in CLRS 407
  16. (12/7) Review for the final exam
  17. Final exam schedule will be determined by the Department Chair and notification will be given several weeks before the end of the semester

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