nm 4103
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
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NM 4103
Radiopharmaceuticals &Quality Control
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What is a Radiopharmaceutical?• Radionuclide
– Allows imaging
• Pharmaceutical– Chosen based on localization
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Ideal Radiopharmaceutical
• Easily produced
• Inexpensive
• Readily available
• Short half-life
• Gamma rays
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Half-Life
• Physical– Time for radionuclide to reduce activity by
one-half
• Biologic– Excretion, perspiration
• Effective– Physical and biologic half-lives
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Common Radionuclides
99mTc - Technetium 6 hours123I – Iodine 13.2 hours131I - Iodine 8 days133Xe - Xenon 5.3 days67Ga - Gallium 78.3 hours111In - Indium 67 hours201Tl – Thallium 73.1 hours
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How do they do that?
• 99mTc eluted from generator Mix Kits Images
• Physiology Methods of localization
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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
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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.
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Methods of localizationCapillary blockage
• Pulmonary capillaries and small arterioles trap larger
particles
• 99mTc MAA particles trapped in the lung capillaries
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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
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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
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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
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Methods of localizationMetabolism• 18F-FDG uptake in myocardial, brain
tissues and tumors
• PET imaging ~ glucose metabolism
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Methods of localizationReceptor binding• 11C-dopamine binding to the dopamine
receptors in the brain ~ Neuroreceptor imaging
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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
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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
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Methods of localizationChemotaxis• 111In labeled leukocytes to localize
infections
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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
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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
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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
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Kits
• Facilitated nuclear pharmacy
• Long shelf-life
• Some are as simple as just adding 99mTcO-
4
• Sterile environment, laminar flow hood,
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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
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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
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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.
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Nuclear Pharmacy
• Lab coat
• Gloves
• Tongs
• Lead barrier shield
• Laminar flow hood
• Aseptic technique
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Dispensing
• Prescription
• Name
• ID number
• Technologist
• Type of radiopharmaceutical
• Dose given
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Pediatric doses
• Biodistribution is different in children
• Dose must be adjusted
• Usually calculated based on weight or body surface area
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Disposal
• Decay in storage ~ most common
• Sewer
• Incineration
• Burial in landfill
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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
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Sewerage system
• Radioactive material must be soluble
• Biologic matter
• Quantity of monthy allowances
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Transfer to an Authorized Recipient• Long-lived radionuclides
• Usually buried or incinerated
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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