nm 4103 radiopharmaceuticals & quality control. what is a radiopharmaceutical? radionuclide...
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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– Time for radionuclide to reduce activity by
one-half
• Biologic– Excretion, perspiration
• Effective– Physical and biologic half-lives
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
How do they do that?
• 99mTc eluted from generator Mix Kits Images
• Physiology Methods of localization
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
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.
Methods of localizationCapillary blockage
• Pulmonary capillaries and small arterioles trap larger
particles
• 99mTc MAA particles trapped in the lung capillaries
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
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
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
Methods of localizationMetabolism• 18F-FDG uptake in myocardial, brain
tissues and tumors
• PET imaging ~ glucose metabolism
Methods of localizationReceptor binding• 11C-dopamine binding to the dopamine
receptors in the brain ~ Neuroreceptor imaging
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
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
Methods of localizationChemotaxis• 111In labeled leukocytes to localize
infections
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
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
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
Kits
• Facilitated nuclear pharmacy
• Long shelf-life
• Some are as simple as just adding 99mTcO-
4
• Sterile environment, laminar flow hood,
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
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
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.
Nuclear Pharmacy
• Lab coat
• Gloves
• Tongs
• Lead barrier shield
• Laminar flow hood
• Aseptic technique
Dispensing
• Prescription
• Name
• ID number
• Technologist
• Type of radiopharmaceutical
• Dose given
Pediatric doses
• Biodistribution is different in children
• Dose must be adjusted
• Usually calculated based on weight or body surface area
Disposal
• Decay in storage ~ most common
• Sewer
• Incineration
• Burial in landfill
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
Sewerage system
• Radioactive material must be soluble
• Biologic matter
• Quantity of monthy allowances
Transfer to an Authorized Recipient• Long-lived radionuclides
• Usually buried or incinerated
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