1. Radiopharmaceuticals & Quality Control
NM 4103
Radiopharmaceuticals &
Quality Control

2. What is a Radiopharmaceutical?
Radionuclide
Allows imaging
Pharmaceutical
Chosen based on localization

3. Ideal Radiopharmaceutical
Easily produced
Inexpensive
Readily available
Short half-life
Gamma rays
Alpha ~ never used for diagnostic: high radiation to the patient
Beta ~ usually used only for therapy

4. Half-Life Physical Biologic Effective
Time for radionuclide to reduce activity by one-half
Biologic
Excretion, perspiration
Effective
Physical and biologic half-lives

5. Common Radionuclides 99mTc - Technetium 6 hours 123I – Iodine
8 days
133Xe - Xenon
5.3 days
67Ga - Gallium
78.3 hours
111In - Indium
67 hours
201Tl – Thallium
73.1 hours

6. How do they do that? 99mTc eluted from generator Mix Kits Images
Physiology Methods of localization
A radionuclide can be combined with various stable compounds that are localized by specific organs.

7. Methods of Localization Passive Diffusion
Compound diffuses across a biologic membrane from a compartment of higher concentration to one of lower concentration.
99mTc-DTPA (brain imaging)
99mTc DTPA aerosol
133Xe ventilation
111In DTPA cisternography
Myocardial perfusion with 99mTc Sestamibi
Filtration of 99mTc DTPA by kidney

8. Methods of localization Ion Exchange (Chemisorption)
The diophosphates are absorbed onto and form a complex with the Calcium Hydroxyapatite crystals. They bind exclusively to the mineral phase of the bone and not to organic matrix.
Phosphate bone-scanning (MDP, HDP)
Where bone modeling is most active is where the highest amount of Tc-MDP accumulates.

9. Methods of localization Capillary blockage
Pulmonary capillaries and small arterioles trap larger particles
99mTc MAA particles trapped in the lung capillaries

10. Methods of localization Phagocytosis
Engulfment and ingestion by specialized cells
Colloid scanning for Liver (middle range particles)
Colloid scanning for the Spleen (largest particles)
Colloid scanning for bone marrow (smallest particles)
Colloid scanning for lymph nodes
Removal of 99mTc sulfur colloid particles by the reticuloendothelial cells in the liver, spleen and bone marrow

11. Methods of localization Active Transport
Movement of a compound across a biologic membrane against a concentration gradient, uphill, from a lower to a higher concentration.
Iodine or Tc for thyroid
Pertechnetate for Meckel’s diverticulum
Pertechnetate for stomach
Pertechnetate for choroid plexus
Pertechnetate for hepatobiliary imaging
Pertechnetate for salivary gland
Thallium in myocardium

12. Methods of localization Cell Sequestration
To separate certain cells apart from the whole
Leukocytes for abscess scanning (WBC)
Labeled platelets
Sequestration of heat-damaged 99mTc labeled rbc’s by the spleen

13. Methods of localization Metabolism
18F-FDG uptake in myocardial, brain tissues and tumors
PET imaging ~ glucose metabolism

14. Methods of localization Receptor binding
11C-dopamine binding to the dopamine receptors in the brain ~ Neuroreceptor imaging

15. Methods of localization Compartmental localization
Partitioning and Retention of the radiopharmaceutical into a biologic compartment.
Cardiac scanning with labeled RBC’s (gated blood pool)
Cisternogram with In111 DTPA (injected intrathecally and confined to CSF
Compartmental Leakage : Labeled RBC’s for GI bleeding detection

16. Methods of localization Antigen-antibody
Specific for a tumor associated antigen imaging
Localizes via an antibody-antigen reaction
Monoclonal antibodies
131 I , 111In and 99mTc labeled antibody to localize tumors
Octreotide,

17. Methods of localization Chemotaxis
111In labeled leukocytes to localize infections

18. Biodistribution
Consists of absorption, distribution, metabolism, plasma clearance and excretion.
Organ systems involved in 99mTc pertechnetate biodistribution:
*Stomach
* Salivary glands
* Thyroid
* Bowel
* Choroid plexus
* Brain
* Sweat glands
* Kidney

19. Reducing agent
Chemically, 99mTcO-4 is nonreactive and won’t label by direct addition of a pharmaceutical compound.
The oxidation state needs to first be reduced to allow reaction (tagging)
Reducing agents:
Stannous chloride (most common)
Stannous citrate, stannous tartrate, ferrous sulfate, sodium borohydride

20. Oxygen in the vial Oxygen can cause oxidation of the stannous ion
Especially before the addition of 99mTc
Free 99mTc
Some kits (MDP,HDP) have an antioxidant to prevent oxidation
Ascorbic acid, gentisic acid

21. Kits Facilitated nuclear pharmacy Long shelf-life
Some are as simple as just adding 99mTcO-4
Sterile environment, laminar flow hood,
New laws

22. Colloids Size falls between a solution and a suspension
Particles range between 10 nm and 1µm
Gelatin : stabilizing agent used to prevent aggregation
Examples : 99mTc Sulfur colloid & 99mTc MAA
Aggregation :

23. Physicochemical Tests
Determine purity and integrity of a radiopharmaceutical
Check for particulate matter, color, clarity
Particle size /number of colloids checked under microscope
pH : 2-9 (ideal is 7.4 ~ same as blood)
Radionuclide Purity : Moly breakthrough
Radiochemical Purity : free 99mTcO-4
Chemical Purity: Aluminum

24. Biologic Tests Sterilization: membrane filtration is most common
Radionuclides can be sensitive to heat sterilization
Sterility testing takes longer than the half-life of radionuclides.
Okay to used as long as the manufacturer has established sterility and apyrogenicity at the production level.

25. Nuclear Pharmacy Lab coat Gloves Tongs Lead barrier shield
Laminar flow hood
Aseptic technique

26. Dispensing Prescription Name ID number Technologist
Type of radiopharmaceutical
Dose given
Can Vary per license
Talk about biodose / udm / paper records, etc..
Some licensing (?called..Jeff Jones workind on) - info required on film

27. Pediatric doses Biodistribution is different in children
Dose must be adjusted
Usually calculated based on weight or body surface area

28. Disposal Decay in storage ~ most common Sewer Incineration
Burial in landfill
*Records
More in chapter 11

29. Decay in Storage Radionuclides with half-lives of 120days or less.
Can be released to waste when:
10 half-lives
Radioactivity cannot be detected above background
Radioactive signs are removed

30. Sewerage system Radioactive material must be soluble Biologic matter
Quantity of monthy allowances
Biologic matter

31. Transfer to an Authorized Recipient
Long-lived radionuclides
Usually buried or incinerated

32. Good Practice Radiation signs Wear Lab coat and gloves Absorbent paper
Lead containers
Film badge
Identify radionuclide containers
Survey work area
Do not eat or drink in radiation lab
Monitor hands and feet