Radiopharmaceuticals & Quality Control 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 Alpha ~ never used for diagnostic: high radiation to the patient Beta ~ usually used only for therapy

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

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

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.

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

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.

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

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

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

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

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

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

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

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,

Methods of localization Chemotaxis 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, New laws

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 :

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. Okay to used as long as the manufacturer has established sterility and apyrogenicity at the production level.

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 Can Vary per license Talk about biodose / udm / paper records, etc.. Some licensing (?called..Jeff Jones workind on) - info required on film

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 *Records More in chapter 11

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 Biologic matter

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