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Diagnostic Imaging Agents by Broox Boze Southern Methodist University What is Diagnostic Imaging? A field of medicine used in determining physiology, managing disease, and locating abnormalities in the body. Diagnostic Techniques X-Ray Imaging CAT or CT Scans Ultrasound Imaging Magnetic Resonance Imaging Scintigraphy (Radionucleotides) Where did it all begin? President Garfield was shot and lived for weeks with a bullet somewhere in his body Alexander Graham Bell though he could develop a sound induction device which would trigger when it came in contact with an item of different density X-Ray Imaging Was the first “Great Discovery” in the field of diagnostic imaging Wilhelm Roentgen was working with light rays of higher density and shorter wavelength than the light filling this room He discovered that a piece of aluminum foil coated in barium platinocyanide showed luminescent properties and began to investigate After months of “playing” with various objects and determining density he discovered that placing his hand between the light source and film resulted in the image of his skeleton The benefits of x-rays far out weigh the potential risks X-rays cause atoms to lose electrons through bombardment with photons Radiolysis cause the formation of the free radicals: HO. and H. Free radicals form hydrogen peroxide and HO2· which are damaging to DNA, stop replication, and result in cell death H· + H· v H2 OH· + OH· v H2O2 H· + OH· v H2O OH· + H2O2 v HO2· + H2O CAT or CT Scans Essentially an x-ray technique Produces more detailed images of internal organs that traditional x-rays Used in diagnosing muscle and bone disorders, locating blood clots, detecting internal bleeding, monitoring diseases such as cancer To enhance imaging patients are given laxatives, enemas, or suppositories. Agents serving to increase contrast by weakening or blocking x-ray transmission include… – – – – Barium (Ba) Barium Sulphate (BaSO4) Iodine (I) Gastrograffin These agents all work in the same way but vary in function by how they are administered Intravenous Agents – Are usually iodine based – Eliminated from the body extremely quickly – Travel through the blood vessels, brain, spine, liver, and kidney Oral Agents – Most common are Barium Sulphate and Gastrograffin administered in a milk shake type formula – BaCl2 (aq) + (NH4)2SO4 (s) -------------> BaSO4 (s) + 2NH4Cl (aq) Rectal Agents – Used in imaging the lower gastrointestinal tract including the large intestine – Not the most comfortable method and can cause constipation, itching, and swelling Ultrasound Imaging The most underdeveloped of the 5 areas Used in imaging solid or water filled organs, including the liver, spleen, kidney, heart, blood vessels, and bladder Performed with a handheld device and is easily portable to patients No Contrast Agents are used on a regular basis but the use of microbubbles has potential – The biggest problem is preventing breakdown in the heart and lungs – A biodegradable shell of polybutyl-2 cyanoacrylate has been shown to work in some cases Magnetic Resonance Imaging Newest and fastest growing field Focuses on smaller and more selective areas than x-rays or CT scans Three important parameters determining image viability – Water Content (proton density) – Blood Flow – Relaxation Time MRI Contrast Agents Contrast Agents are usually paramagnetic metal systems which function by altering hydrogen nuclei of water protons Are classified as T1 or T2 agents Four Types of Magnetic Fields – Diamagnetic agents are useful in gastrointestinal imaging – Superparamagnetic and Ferromagnetic agents which have a net magnetic dipole larger than the sum of unpaired electrons. Dephasing of protons shortens T2 – Paramagnetic agents include oxygen, nitroxides, and ions of the metals Fe, Mg, Gd, and Dy, all of which have unpaired electrons and result in positive enhancement Toxicity of paramagnetic agents can be reduced by gadolinium chelates Gd-DTPA was the first IV MRI agent approved The nonionic forms (Gd-DTPA-BMA and Gd-DOTA) quickly followed These agents differed in charge and number of gadolinium complexes which increased stability and altered viscosity Scintigraphy The only imaging technique entirely dependant on contrast agents Radionucleotides are drugs that contain some radioactive element. They are typically small organic molecules, such as peptides, but can also be macromolecules such as antibodies. All the radionucleotides used in diagnostic imaging are artificially produced in a cyclotron or radioisotope generator Technetium (Tc-99m) Technetium pharmaceuticals are metal-electron donor complexes Tc is an electron deficient metal and therefore interacts with electronegative groups Produced using the molybdenum-99/technetium99 system where molybdenum is obtained as a fission product of uranium Iodine used in imaging blood vessels and solid organs The original Iodine contrast agents had triiodinated benzoic acid salts that dissociated in water to give 3 iodides for every 2 molecules of water in solution – Drugs include diatrizoate and iothalamate Newer agents have a higher ratio of iodine which improves its function Low osmolar contrast agents can be used in smaller doses and are much safer than the previous drugs These drugs are 20 times the cost of high osmolar contrast agents Indium Indium-111 is used in brain studies Most stable in acid solutions below ph 3.5 Functions by binding to somatostatin receptors throughout the body Fluorine Fluorine-18 decays to oxygen-18 by electron capture and then aids imaging by emitting gamma rays. Fluorodeoxyglucose is used in PET Scans along with Carbon-11, Oxygen-15, and Nitrogen-13 To Sum It All Up…