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NM 4103

NM 4103. Radiopharmaceuticals & Quality Control. What is a Radiopharmaceutical?. Radionuclide Allows imaging Pharmaceutical Chosen based on localization. Ideal Radiopharmaceutical. Easily produced Inexpensive Readily available Short half-life Gamma rays. Half-Life. Physical

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NM 4103

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  1. 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

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

  5. Common Radionuclides

  6. How do they do that? • 99mTc eluted from generator Mix Kits Images • Physiology Methods of localization

  7. Methods of LocalizationPassive 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 localizationIon 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 localizationCapillary blockage • Pulmonary capillaries and small arterioles trap larger particles • 99mTc MAA particles trapped in the lung capillaries

  10. Methods of localizationPhagocytosis • 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 localizationActive 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 localizationCell 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 localizationMetabolism • 18F-FDG uptake in myocardial, brain tissues and tumors • PET imaging ~ glucose metabolism

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

  15. Methods of localizationCompartmental 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 localizationAntigen-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

  17. Methods of localizationChemotaxis • 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,

  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

  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.

  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

  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

  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

  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

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