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PRODUCTION OF RADIONUCLIDES
NUCLEAR STABILITY
- There are approx 275 diff nuclei that have shown no evidence of radioactive decay: stable - N/P ratio is too high (neutron rich) production of negative beta particle. - N/P ratio is too low (neutron poor) net conversion of proton to neutron
Positron emission Absorption by the nucleus of an orbital electron (electron capture of EC)
This excitation energy is removed eother by gamma-ray emission or by process of internal conversion. Ex. Tc-99m w/c decays with a half life of 6 hrs to Tc 99
The transition of a radionuclide from an upper energy state to a lower energy state by the emission of gamma rays is reffered to as an isometric transition.
If a nucleus is capable of emitting a gamma ray, a probability that the photon may eject an electron from extranuclear shell referred as internal conversion. Upper level electron undergoes transition to occupy lower energy electron site, an x-ray is emitted. These x-rays that may cause the ejection of an additional outer shell electron known as Auger electron. Positron decay leaves daughter nuclide two electron mass units lower than the parent, requiring at least 1.022 MeV (2 X 0.511 MV/electron) of transition energy Alpha decay occurs primarily for nuclei heavier than lead.
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Accelerator-produced radionuclides
Accelerators are devices that increase the energy of charged particles to enable a nuclear reaction upon impact w/ a target Either cyclotron or linear accelerator can be used to produce radionuclides, depending on the type of nuclear reaction and the yield desired
Generator Systems
Certain parent daughter sys involve a long lived parent radionuclide that decays to a short live daughter The long lived parent produces a continuous supply of the relatively short live daughter radionuclide and is therefore called generator 2 types of parent-daughter relationships:
Transient Equilibrium
Half-life of the parent is a factor of 10-100 times greater than that of the daughter Ex. Mo 99 Tc 99m Mo-99, 67 hr half-life and Tc-99m, 6 hr half-life
Secular Equilibrium
The half-life of parent is 100-1000 times greater than that of the daughter Ex. Sn-113, 115 days half-life to In-113m, 1.7 hr half-life
RADIOPHARMACEUTICALS
TECHNETIUM RADIOPHARMACEUTICALS
Tc-99m 1937, Perrier and Segre in a sample of Mo-99 that had been irradiated by neutrons and deuterons
1957 Mo-99 Tc-99m generator, Brookhaven National Laboratory 1961, University of Chicago Physical Properties: 1. Half life of 6 hr 2. 140 keV photon (88% abundance)
TECHNETIUM RADIOPHARMACEUTICALS.....
Provides good tissue penetration and imaging capabilities for use w/ gamma camera No beta decay providing low radiation absorbed dose Ready availability from the Mo-99 to Tc99m generator
Ga-67, 93 keV(40%), 184 keV(24%), 296 keV(22%) and 388 keV(7%) In-111, 173 keV(89%) and 247 keV(94%)
Gamma energies of In-111 are in the optimum range of detectability for the Gamma Camera
Abundance of gamma emissions provides 183 photons for every 100 disintegrations
Although the gamma energies of Ga-67 are in a range suitable for detection, their abundances are low
Over twice as much Ga-67 and In-111 would need to be injected to obtain a comparable image
Ga-68 is used to prepare radiopharmaceuticals for PET imaging Ga-68 citrate is used in studies of regional plasma volume
THALLIUM CHLORIDE
Tl-201 is a monovalent cationic metal used in cardiac imaging Obtained from Pb-201 Tl-201 generator Pb-201 bombarded by natural thallium metal with protons with this nuclear reactions:
THALLIUM CHLORIDE.....
Thallium clears rapidly from the blood, w/ maximum concentration on the heart at approx. 10 30 min after injection in the resting state and at 5 min after stress induced either by exercise or pharmacologic intervention at the time of administration Uptake of Tl-201 into the myocardium occurs in proportion to blood flow Adequate tissue oxygenation required to support Tl-201 uptake on myocardial cells
IODINATED RADIOPHARMACEUTICALS
Sodium Iodide, I-123 or I-131 labeled used for thyroid imaging, uptake measurements, and therapy (in the case of I-131) as a capsule or a solution for oral administration I-123 (t 13.2 hr) decays by EC, 159 keV emission (83%) I-131 (t 8 days) decays by B-emission with subsequent gamma emission of 364 keV (82%)
Also been used to label monoclonal antibodies for in vivo tumor imaging and therapy
IODINATED RADIOPHARMACEUTICALS...
I-125 (t 60 days) decays by EC with a 35 keV gamma used to measure plasma volume I-125 labeled antibodies used for radioimmunoassay To label proteins, particularly antibodies, w/ iodine it is important to use mild iodination agents that do not denature the protein Iodination of proteins involves the formation of positively charged iodine species that react w/ various group of the protein
IODINATED RADIOPHARMACEUTICALS...
Some of the most commonly used method for iodination of proteins 1. I2 iodination 2. Iodine monochloride iodination 3. Chloramine T iodination 4. Enzymatic iodination 5. Indirect iodination 6. Iodogen iodination
PET RADIOPHARMACEUTICALS
O-15 (t 2 min), 1.72 MeV N-13 (t 10 min), 1.19 MeV C-11 (t 20 min), 0.96 MeV F-18 (t 110 min), 0.64 MeV The short half-lives of these isotopes require production and radiopharmaceutical synthesis close to where the PET imaging takes place It often require an on-site cyclotron, however F-18 labeled radiopharmaceutical, centralized radiopharmacies that supply regional hospitals and PET centers are becoming common
THERAPEUTIC RADIOPHARMACEUTICALS
Sodium P 32 phosphate is an FDA approved radiopharmaceutical for treatment of polycythemia vera, chronic myelotic leukemia, chronic lymphocetic leukemia and for palliation of metastatic bone pain Chromic P 32 phosphate = suspension of P32 used for intracavitary installation for treatment of peritoneal or pleural effusions caused by metastatic disease P 32, B-decay emission with t of 14.3 days
RADIONUCLIDIC PURITY
It is the proportion of the total radioactivity present as the stated radionuclide Measurement requires determination of the identity and amounts of all radionuclide presents Radionuclidic impurities can have significant effects on the overall radiation dose to the patient and the quality if the image obtained The identities and amounts of radionuclidic impurities found in a radiopharmaceutical depend on the method of radionuclidic production used
RADIOCHEMICAL PURITY
Defined as the proportion of the stated radionuclide that is present in the stated chemical form Or the percentage of the total radioactivity in a specimen that is in the specified or desired chemical form Ex. If 5% of the Tc-99m activity remains as free pertechnetate in a radiolabeling procedure, the radiochemical purity would be stated as 95%, assuming no other impurities Rad absorbed dose, biologic distribution and the quality of the image are directly related to the radiochemical purity
RADIOCHEMICAL PURITY.....
Chromatographic methods to determine radiochemical impurity, including gelpermeation chromatography, gas liquid chromatography and paper chromatography Chromatography involves the separation of chemical mixture into its components along a stationary phase (absorbent) as a result of different velocities in the mobile phase (migrating solvent)
RADIOCHEMICAL PURITY.....
Radiochromatography the presence of the component is determined by the location of its radioactivity ratherthan by some other physical or chemical property
Useful for sterilizing preparation vials and other handling utensils and materials but is not useful for any of the RP used in clinical practice
Special small pore filters w/ diameters smaller than microorganisms have been developed Filter opre size of 0.22 is required for sterilization This size will trap bacteria, including small organisms such as Pseudomonas
Pyrogens are metabolites of microorganisms or other contaminating substances that cause febrile reaction They can be present even in sterile preparations The typical clinical syndrome is fever, chills, joint pain, and headaches developing minutes to a few hours after injection The pyrogenic reaction lasts for several hours and alone is not fatal
2. LINEARITY
- Designed to determine the response of the calibrator over a range of measured activities
4. GEOMETRY
- Performed during acceptance testing of the dose calibrator - If readings vary by more than 10% from one volume to another, correction factors are calculated