Radiopharmaceuticals: Nuclear Decay, Alpha Particles, Beta Decay - PDF

Radiopharmaceuticals 1  Overview of atom  All substances are made of atoms which have electrons around the outside and a nucleus at the center.  The nucleus consists of protons & neutrons.  The atomic number (Z) is the # of protons in an atom’s nucleus.  The...

Radiopharmaceuticals 1  Overview of atom  All substances are made of atoms which have electrons around the outside and a nucleus at the center.  The nucleus consists of protons & neutrons.  The atomic number (Z) is the # of protons in an atom’s nucleus.  The atomic mass (A) is the # of protons + neutrons in its nucleus.  An elemental species characterized by its mass number ‘A’ and its atomic number ‘Z’ is called Nuclide. 2 9  Overview of atom…  Isotopes of an element are nuclides with the same atomic number ‘Z’ but different mass numbers ‘A’.  Eg: carbon-12, carbon-13, carbon-14 Unstable isotopes Eg: C-14 Isotopes Stable isotopes Eg:C-12 and C-13 3 3  What makes nucleus unstable?  In the nucleus there are two important forces electrostatic force and strong nuclear force.  The imbalance b/n this two forces make a nucleus of an atom unstable. That is Strong Nuclear force >< Electrostatic Unstable nucleus force  Hence for a nucleus to be stable there must be some kind of balance b/n this two forces forces. 4  What makes nucleus unstable? This forces are mainly determine by 1. Neutron to Proton Ration (N/P):  For stable atom with P < 20 the ration is 1, for those having P > 20 the ratio is about 1.5.  Thus deviation from this makes a nucleus unstable. 2. Nuclear size (size of the nucleus)  Large or heavy nucleus are unstable b/c the strong nuclear force will fail to hold the nucleus together.  NB: strong nuclear force acts within short distance 5 How does unstable nucleus become stable?  Unstable atomic nucleus spontaneously loses energy by emitting ionization particles and radiation through a process called Radioactive decay. Daughter nuclide Unstable nucleus Parent nuclide More Stable daughter nucleus 6 9  Radioactivity  Radioactivity: is the phenomenon of emission of radiation (gamma rays) and/or particles (alpha and beta particles) owing to the spontaneous disintegration of unstable nucleus (radionuclide).  This radio activity could be of two types   Natural radioactivity: Nuclear reactions occur spontaneously.  Artificial radioactivity: obtained from an artificially induced unstable nucleus using such as particle bombardment or irradiation. 7  Modes of radioactive decay  When an unstable nucleus decays, It may give out: Gamma ray (γ) Alpha particle(α) Beta particle() 8  Alpha(α) particle decay  Alpha particles are made of 2 protons and 2 neutrons.  They can be written as 2α , or 2He , because they're the 4 4 same as a helium nucleus.  This means that when a nucleus emits an alpha particle, its atomic number decreases by 2 and its atomic mass decreases by 4. A Z X A4 Z2 Y  4 2 He 2 9  Alpha(α) particle decay…  Alpha particles are relatively slow and heavy.  They have a low penetrating power so one can stop them with just a sheet of paper.  Because they have a large charge, alpha particles ionize other atoms strongly.  Alpha-decay occurs in very heavy elements, for example, Uranium and Radium. 10  Alpha(α) particle decay… 11  Alpha(α) particle decay…  Used only for therapeutic purposes. Their clinical use is very limited, and they are mainly used for research purposes  Advantage: they do not present a hazard from exposure external to the body.  However, due to the very large number of ionizations they produce in a very short distance, alpha emitters can present a serious hazard when they are in close proximity to cells and tissues such as the lung. Special precautions are taken to ensure that alpha emitters are not inhaled, ingested or injected. 12  Beta() particle decay Modes of  decay A. Electron emission (Beta-Minus Decay)  Beta-minus (-) decay characteristically occurs with radio nuclides that have an excess number of neutrons compared with the number of protons (i.e., has a higher N/Z ratio compared to the stable nucleus)  In - decay, a neutron (n) essentially decays into a proton (p) and a - particle NP+ + e- (- particle) 13  Beta() particle decay…  This means that when a nucleus emits a β ̅ particle: the atomic mass is unchanged and the atomic number increases by 1. A Z A X Z1Y  β- 14  Beta() particle decay… 15  Beta() particle decay… B. Positron emission (β+ Decay)  Nuclei that are ‘‘neutron deficient’’ or ‘‘proton rich’’ (i.e., have an N/Z ratio less than that of the stable nuclei) can decay by β+ -particle emission  In β+ decay, a proton transforms into a neutron by emitting a β+ -particle  The daughter nuclide has an atomic number that is 1 less than that of the parent P+ N+ e+ (+ particle) 16  Beta() particle decay… A X Y  β A  Z Z-1 17  Beta() particle decay…  Beta particles are much less massive (light) and less charged than alpha particles and interact less intensely with atoms in the materials they pass through,  This gives them a longer range than alpha particles.  Beta particles have a medium penetrating power - they are stopped by a sheet of aluminium.  Beta emitting radionuclide are used mainly for therapeutic purposes in radiopharmacy (nuclear medicine) 18  Gamma(γ) particle decay  Gamma rays are waves, not particles which means that they have no mass and no charge.  In Gamma decay:  atomic number unchanged  atomic mass unchanged.  Gamma rays have a high penetrating power - it takes a thick sheet of metal such as lead to reduce them. 19  Gamma(γ) particle decay…  Gamma rays do not directly ionize other atoms, although they may cause atoms to emit other particles which will then cause ionization.  We do not find pure gamma sources – they are emitted alongside alpha or beta particles.  When used in diagnostic gamma rays are powerful enough to be detected outside the body of the patient  Useful gamma sources include Technetium-99m, which is used as a "tracer" in medicine which is a combined beta and gamma source.  It is chosen because betas are less harmful to the patient than alphas (less ionization) 20  Summary of particles  Alpha particles are easy to stop, gamma rays are hard to stop. 21  Summary of particles… Type of Radiation Alpha particle Beta particle Gamma ray Symbol or Charge +2 -1 0 Speed slow fast Very fast Ionising ability high medium 0 Penetrating power low medium high Stopped by: paper aluminium lead 22  Radiation measurement The basic unit for quantifying radioactivity (i.e. describes the rate at which the nuclei decay). Curie (Ci):  Curie (Ci), named for the famed scientist Marie Curie Curie = 3.7 x 1010 atoms disintegrate per second (dps) Millicurie (mCi) = 3.7 x 107 dps Microcurie (μCi) = 3.7 x 104 dps Becquerel (Bq): A unit of radioactivity. One Becquerel is equal to 1 disintegration per second. 23 Properties of an ideal diagnostic radioisotope  Types of Emission: Pure gamma emitter  Energy of Gamma Rays: 100-250 keV e.g. 99mTc, 123I,  Easy Availability: Readily Available, Easily Produced & Inexpensive: e.g. 11C vs. 99mTc  Effective Half-life: half life relatively short to reduce radiation dose and long enough to perform the procedure  Example: For a Bone Scan which is a 4-h procedure, 99mTc- phosphate compounds with an effective half-life of 6 h are the ideal radiopharmaceuticals.  Patient Safety: Should exhibit no toxicity to the patient  Preparation: Should be simple with little manipulation 24  Radiopharmaceuticals Radiopharmaceuticals are medicinal formulations containing radioisotopes which are safe for administration in humans for diagnosis or for therapy or A radioactive drug that can be administered safely to humans for diagnostic and therapeutic purposes. 95% for diagnostic purposes vs the rest for therapeutic treatment 25  Production of radionuclides Three methods to produce radionuclides Charged particle bombardment Protons (1 1H), Deuterons (2 1H), Alpha particles (4He) Neutron bombardment Radio nuclide generator system 26  Production of radionuclides… 1. Charged particle bombardment  Radionuclides may be produced by bombarding target materials with charged particles in particle accelerators such as cyclotrons.  A cyclotron consists of : Two flat hollow objects called Dees and they are part of an electrical circuit.  On the other side of the dees are large magnets that (drive) steer the injected charged particles (protons, deutrons, alpha and helium) in a circular path.  The charged particle follows a circular path until the particle has sufficient energy that it passes out of the field and interact with the target nucleus. 27  Production of radionuclides… Cyclotron 28  Production of radionuclides… 29 29-May-19  Production of radionuclides… 2. Neutron bombardment  Radionuclides may be produced by bombarding target materials with neutrons in nuclear reactors.  The majority of radiopharmaceuticals are produced by this process. 30  Production of radionuclides… 3. Radionuclide generator systems Principle:  A long-lived parent radionuclide is allowed to decay to its short- lived daughter radionuclide and the latter is chemically separated in a physiological solution. Example:  Technetium-99m, obtained from a generator constructed of molybdenum-99 absorbed to an alumina column. 31  Production of radionuclides… 3. 99Mo/99mTc generator 32  Preparation of radiopharmaceuticals  Radiopharmaceutical products include inorganic compounds, organic compounds, peptides, proteins, monoclonal antibodies and fragments and oligonucleotides labeled with radionuclide  Pharmaceuticals and Radionuclides Compounding:  Can be as simple as: adding a radioactive liquid to a commercially available reagent kit  Can be as complex as:  the creation of a multi-component reagent kit 33  Preparation of radiopharmaceuticals…  Kit for radiopharmaceutical preparation  means a sterile and pyrogen-free reaction vial containing the non radioactive chemicals [e.g., complexing agent (ligand), reducing agent, stabilizer, or dispersing agent] that are required to produce a specific radiopharmaceutical after reaction with a radioactive component. 34  Preparation of radiopharmaceuticals… 99mTc radiopharmaceuticals  More than 80% of radiopharmaceuticals used in nuclear medicine are 99mTc-labeled compounds.  Has favorable physical and radiation characteristics.  6-hr physical half-life  Low radiation dose to the patient  Monochromatic 140-keV photons (give images of superior spatial resolution)  Available in a sterile, and pyrogen-free state from 99Mo–99mTc generators. 35  Preparation of radiopharmaceuticals…  The basic principle of 99mTc-labeling involves reduction of 99mTc7+ to an oxidation state that binds to a chelating molecule of interest.  In most cases, kits for 99mTc-radiopharmaceuticals are commercially available for routine clinical use. These kits contain the chelating agent of interest and the reducing agent (usually Sn2+ ion) in appropriate quantities. 36  Preparation of radiopharmaceuticals…  99mTc-Phosphonate Radiopharmaceuticals  Phosphonate compounds localize avidly in bone and, therefore, are suitable for bone imaging.  99mTc-Albumin Colloid : useful for bone marrow imaging  99mTc-Hexamethylpropylene Amine Oxime (HMPAO) is useful in brain perfusion imaging  99mTc-Gluceptate is useful for renal imaging. 37  Storage of radiopharmaceuticals  Should be properly stored so that they are not degraded by light or temperature.  For example ⚫99mTc-labeled macroaggregated albumin should be stored at 2 to 4oC to prevent any bacterial growth and denaturation of proteins, ⚫99mTc-sulfur colloid can be stored at room temperature without any adverse effect.  Since radiation exposure is a serious problem in the nuclear pharmacy, the vials or syringes containing radiopharmaceuticals must be stored in a shielded area. 38  Radiopharmaceuticals quality control  Visual Inspection of Product  Visual inspection of the compounded radiopharmaceutical shall be conducted to ensure the absence of foreign matter and also to establish product identity by confirming that (1) a liquid product is a solution, a colloid, or a suspension. (2) a solid product has defined properties that identify it.  Assessment of Radioactivity  The amount of radioactivity in each compounded radiopharmaceutical should be verified and documented prior to dispensing, using a proper standardized radionuclide (dose) calibrator. 39  Application of Radiopharmaceuticals  Diagnostic (Imaging)  Therapeutic  Tracer  Theranostics treatment: Both therapy and imaging at the same time 40  Application of Radiopharmaceuticals… 1- Radiopharmaceuticals diagnostic purpose  The radiopharmaceutical accumulated in an organ of interest emit gamma radiation which are used for imaging of the organs with the help of an external imaging device called gamma camera.  Two types of diagnostic procedures ⚫ PET (positron emission tomography) ⚫ SPECT (single photon emission computed tomography) 41  Application of Radiopharmaceuticals… PET imaging  Commonly used gamma source: F-18 (but C-11,N-15,O-15) Procedure  Formulate F-18 by attaching to sugar compound called florodeoxyglucose (FDG)  The formulated Cpd is given to the patients IV  FDG is absorbed by cancer cells  The patients rests for sometime until the isotope is accumulated in the lesion and decays by emitting positrons 42  Application of Radiopharmaceuticals… PET imaging…  When the patient enters the imaging camera, each positrons released by RAP travels into the patients tissue and hitting the electrons inside each cells  The interaction b/n positron and electron produces two rays of gamma radiation which are emitted in opposite direction and  The computer connected to the camera calculates the point of origin of the rays and produces metabolic image of the lesion. 43  Application of Radiopharmaceuticals… SPECT imaging  Commonly used gamma source:TC-99m (but I- 123,In-111)  Tc is injected to the patients and into the target lesion whose image is needed  Once it gets into the lesion, it starts emitting radiation  Then, the SPECT camera surrounding the patient catches the photons from the radiation one by one  Finally, the computer gives the metabolic image 44  Application of Radiopharmaceuticals… 45  Application of Radiopharmaceuticals… 2- Radiopharmaceuticals for Treatment purpose They are radiolabelled molecules designed to deliver therapeutic doses of ionizing radiation to specific diseased sites.  Chromic phosphate P32 for lung, ovarian, uterine, and prostate cancers  Sodium iodide I 131 for thyroid cancer  Samarium Sm 153 for cancerous bone tissue  Sodium phosphate P 32 for cancerous bone tissue and other types of cancers  Strontium chloride Sr 89 for cancerous bone tissue  Iridium-192 for cervical and prostate cancer 46  Application of Radiopharmaceuticals… 3- Radiopharmaceuticals as a Tracer  Radiopharmaceuticals with Gamma source: Technetium-99m  Use: to test new pharmaceuticals : to trace inflammation or the presence of blockage in the body  Radiopharmaceuticals used in tracer techniques for measuring physiological parameters (e.g. Chromium-51 (51Cr)-EDTA for measuring glomerular filtration rate). 47  Application of Radiopharmaceuticals… 4- Theranostics : dual purpose  Used for diagnosis and therapy at the same time  Sources: lutetium-177m (177m Lu), Iridium-192 (192Ir)  First, RAP is attached to peptide ligand and a chelator which is capable of catching unstable atom and injected into the patient  Tumor cells attract peptides like a magnet and the peptide fix itself on the cell  Once inside the tumor cell the peptide release both γ and  at the same time o γ- used to make SPECT image o - destroys the tumor  The death of the tumor is monitored by SPECT camera and confirmed by the disappearance of black spot in the image 48  Radioactive waste disposal  Radioactive waste generated in nuclear medicine or pharmacy (e.g., syringes, needles, vials containing residual activities, liquid waste, gas, and contaminated papers, tissues, and liners) is disposed of by the following methods:  Decay-in-storage  Release into a sewerage system  Transfer to an authorized recipient (commercial land disposal facilities) 49  Radioactive waste disposal… Decay-in-storage  Radionuclides with half-lives less than 120 days usually are disposed of by this method.  The waste is allowed to decay for a period of time and then surveyed. If the radioactivity of the waste cannot be distinguished from background, it can be disposed of in the normal trash after removal of all radiation labels.  This method is most appropriate for short-lived radionuclides such as 99mTc, 123I, 201Tl, 111In, and 67Ga, and therefore it is routinely employed in nuclear medicine.  Radioactive waste should be stored separately according to the similar half-lives of radionuclides for convenience of timely disposal of each radionuclide. 50  Radioactive waste disposal… Release into a Sewerage System  Radioactive waste disposal into a sewerage system is permitted provided the radioactive material is soluble (or dispersible biological material) in water.  Disposal depends on the flow rate of water but is limited to 1 Ci (37 GBq) of 14C, 5 Ci (185 GBq) of 3H, and 1 Ci (37 GBq) for all other radionuclides annually. 51  Radioactive waste disposal… Transfer to an Authorized Recipient  A transfer to an authorized recipient method is adopted for long-lived radionuclides  Usually involves transfer of radioactive waste to authorized commercial firms that bury or incinerate at approved sites or facilities. 52  Incompatibilities 53  Incompatibilities  Occasionally, the drugs we use to improve a person's condition may not work in the manner intended.  There are instances when a drug used simultaneously with another drug or substance does not perform as it was intended.  These drugs or substances may be incompatible together and, therefore, should not be administered at the same time.  A drug incompatibility can also occur when drugs are compounded together 54  Incompatibilities… Definition of Drug Incompatibility:  Drug Incompatibility refers to interactions between two or more substances which lead to changes in chemical, physical, therapeutic properties of the pharmaceutical dosage form. Types of Drug Incompatibility 1. Therapeutic incompatibility 2. Physical incompatibility 3. Chemical incompatibility 55  Incompatibilities… Therapeutic incompatibility  Therapeutic incompatibilities occur when agents antagonistic to one another are prescribed together. 56  Incompatibilities… Physical Incompatibility  Physical incompatibilities are often called pharmaceutical incompatibilities.  Def.: Interaction between two or more substances which lead to change in color, odor, taste, viscosity and morphology.  Example  Insolubility of prescribed agent in vehicle  Immiscibility of two or more liquids  Precipitation due to decreased solubility (called salting out)  Liquefaction of solids mixed in a dry state (called eutexia) 57  Incompatibilities… Chemical incompatibilities  Reaction between two or more substances which lead to change in chemical properties of pharmaceutical dosage form.  Example  Oxidation  Hydrolysis  Formation of insoluble complexes 58  Drug-excipients interaction  The successful formulation of a stable and effective dosage form depends on the careful selection of the excipients.  Despite the earlier account of excipients acting as stabilizers, it is fair to state that there are far more cases on record of excipients adversely affecting quality.  Degradation may be caused by interaction between functional groups in the excipient and those associated with the drug. 59  Drug-excipients...  Chemical interaction can result in degradation of the drug substance to inactive moieties with loss of efficacy where degradation is excessive.  Even when degradation is modest, it is possible that the formed degradation products may compromise safety.  Physical interactions between drug and excipient also can compromise quality. 60  Drug-excipients...  Excipients may contribute to degradation even when not directly interacting with active moieties.  Soluble materials may alter pH or ionic strength, thereby accelerating hydrolytic reactions in liquid presentations. 61 62 29-May-19 Radiopharmaceuticals  quiz(24/04/2017)C 1C 2C 1.Mention 2 Examples of 1. Mention 2 examples of Chemical incompatibilities Physical Incompatibility 2. What is Theranostics. 2. Which methods of waste 3.What are methods are used disposal of will be best for to produce radionuclides long-lived radionuclides 4.Alpha particles can be 3. What makes nucleus stopped by. unstable. 4. the particle that have no mass and no charge is... 63