Hospital Pharmacy Lecture 5 (Fall 2023-2024) PDF

HOSPITAL PHARMACY Fall 2023-2024 Noha Alaa Hamdy, Pharm D, PhD Assoc. Prof. of Clinical Pharmacy Faculty of Pharmacy Alexandria University Lecture 5 Radiopharmaceuticals Noha Alaa, PharmD, PhD 2  At the end of this lecture, you will be...

HOSPITAL PHARMACY Fall 2023-2024 Noha Alaa Hamdy, Pharm D, PhD Assoc. Prof. of Clinical Pharmacy Faculty of Pharmacy Alexandria University Lecture 5 Radiopharmaceuticals Noha Alaa, PharmD, PhD 2  At the end of this lecture, you will be able to:  Define radiopharmacy & radiopharmaceuticals.  Explain the uses of radiopharmaceuticals. Intended  Enumerated radionuclides used in medicine Learning  Understand the principle of 99m Tc production Outcomes  Demonstrate the preparation of 99m Tc from 99 99m Mo / Tc generator  Explain the facilities & radiation protection in the radiopharmacy Noha Alaa, PharmD, PhD 3  Radiopharmacy (also known as Nuclear Pharmacy) is the speciality practice of pharmacy that focuses on the safe and efficacious use of radioactive drugs. Radiopharmacy Radioactive drugs, usually referred to as Radiopharmaceuticals radiopharmaceuticals (as stated by WHO). Radiopharmaceuticals are unique medicinal formulations containing radioisotopes which are used in major clinical areas for diagnosis and/or therapy. Noha Alaa, PharmD, PhD 4  A radiopharmaceutical consists of both a drug component and a radioactive component. The drug component is responsible for the localization in specific organs or tissues. The radioactive component is responsible for the emission of gamma rays for external detection in diagnostic imaging and/ or particulate radiation for radionuclide therapy. Noha Alaa, PharmD, PhD 5  Diagnostic Therapeutic radiopharmaceuticals radiopharmaceuticals  are intended for use in the diagnosis and/or monitoring of  are intended for use in the various disease states. treatment of various  Relatively small radiation doses disease states. are delivered.  Relatively large radiation  Examples include: doses are delivered to Uses  99mTc diphosphonates for cause localized radiation bone imaging procedures damage.  99mTc macroaggregated  Example: 131I sodium albumin for lung imaging iodide for treatment of procedures thyrotoxicosis or thyroid  201Tl thallous chloride for cancer. myocardial perfusion imaging procedures. Noha Alaa, PharmD, PhD 6 Noha Alaa, PharmD, PhD 7  1- Charged particle bombardment Radionuclides may be produced by Production of bombarding target materials with radionuclides: charged particles in particle accelarators such as cyclotrons. 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. Noha Alaa, PharmD, PhD 8  https://www.youtube.com/watch?v=6BxyqFK2KRI Cyclotron Noha Alaa, PharmD, PhD 9  2- Neutron bombardment Radionuclides may be produced by bombarding target materials with neutrons in nuclear reactors Production of radionuclides: Noha Alaa, PharmD, PhD 10  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: Production of - Technetium-99m, obtained from a generator radionuclides: : constructed of molybdenum-99 absorbed to an alumina column. Eluted from the column with normal saline Noha Alaa, PharmD, PhD 11 Radionuclides used in nuclear medicine Noha Alaa, PharmD, PhD 12   Alpha-decay is the process whereby a nucleus emits a helium nucleus, or alpha-particle.  Because they are heavy & positively charged, Alpha- alpha-particles travel only short distances (they emitters have a low penetrating power).  Their ionizing nature would result in highly localized radiation dose if taken internally and hence they tend NOT to be used in radiopharmaceuticals.  Alpha-decay occurs in very heavy elements, for example, Uranium and Radium. Noha Alaa, PharmD, PhD 13  Beta-decay occurs in two ways, one that involves the emission of a: BETA- Negatively Positively EMITTERS charged charged ¯ Beta -particle + Beta -particle or electron or positron Noha Alaa, PharmD, PhD 14   Radionuclide which decay by beta¯ - decay tend ¯ to have nuclei that are neutron rich. Beta -  They attempt to reach a more stable state by the emitters transformation of a neutron into a proton with the emission of a beta ¯ - particle.  They have medium penetrating power  Their range in tissues is only a few millimeters. Because of this and their highly ionizing nature, beta ¯ - emitters tend to be used in therapeutic radiopharmaceuticals. Noha Alaa, PharmD, PhD 15   The principle of therapeutic treatment with radionuclides is to target the radionuclide to a specific Beta¯- tissue within the body in an attempt to selectively damage or destroy that tissue. emitters  Ideally therapeutic beta ¯ - emitting radionuclides should have a half-life of several days to provide a prolonged radiobiological effect. Noha Alaa, PharmD, PhD 16   The most widely used example of this is 131I – sodium iodide capsules, half-life 8 days, which is used in the treatment of hyperactive thyroid disease and in certain ¯ Beta - thyroid tumors.  Since thyroid tissue normally takes up iodine in the emitters normal synthesis of the hormone levothyroxine, radioactive iodine is also taken up and held in the thyroid tissue. Hence the radiation damage is targeted to the thyroid tissue specifically & the normal excretion of any excess iodine results in no significant damage to other organs and tissues. Noha Alaa, PharmD, PhD 17   In this transformation, a proton-rich nuclide attempts Beta+ - to achieve stability by converting a proton to a neutron emitters with the emission of a positron  The positron is very short-lived, so it interacts with an electron resulting in the conversion of both particles into two gamma-rays, which are emitted at an angle of 180° to each other. Noha Alaa, PharmD, PhD 18   Gamma rays are waves, not particles. This means that they have no mass and no charge.  in Gamma decay: Gamma rays - 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.  Positron emission tomography (PET) uses specialized gamma-camera with detectors placed 180°apart, to create images in all three dimensions. Beta+ -  18F labelled glucose, known as 18F-fluoro emitters deoxy-glucose (18F- FDG), is the most commonly used PET radiopharmaceutical in hospital practice with a half-life of 109.8min and used for tumor detection. PET imaging with 18F- FDG, in combination with X-ray computerized tomography (CT) is rapidly becoming an important imaging technique in the diagnosis of cancer. Noha Alaa, PharmD, PhD 20  Adsorption Cyclotron by an anion- exchange resin 18F- FDG Quality Radio-synthesis in an control automated apparatus production: analysis (synthesis module) Sub-dispensing is carried out using robotic dispensing Filtration systems. Sterilization through 0.2μm filter High temperature for short sterilization Noha Alaa, PharmD, PhD cycles 21   Nuclei that are proton rich may, as an alternative to positron emission, capture electrons from the atom’s electron orbital.  This process results in the transformation of a proton to a neutron within the nucleus. The subsequent rearrangement of the electrons orbiting the nucleus ELECTRON results in a characteristic emission of X-rays or gamma CAPTURE rays (e.g. 123I: 12353I + electron → 12353Te + gamma).  Radionuclides which decay by electron capture are useful in diagnostic imaging since they emit gamma-rays, ex. 123I: Sodium iodide injection, half-life 13h, used in Thyroid imaging. Noha Alaa, PharmD, PhD 22  Some radionuclides exist for measurable periods in excited, or isomeric, states prior to reaching ground state.  This form of decay involves the emission of a gamma-ray and is known as isomeric transition.  When radionuclides exist in this transitional state, they are known as metastable, which is denoted by the letter ‘m’ ex. 99mTc. ISOMETRIC TRANSITION Diagnostic imaging 99Mo decays by beta ¯- emission to the ground state 99Tc either directly or indirectly. The indirect route, the most common, involves the isomer 99mTc, which in turn decays from its metastable to 99Tc by isomeric transition. Noha Alaa, PharmD, PhD 23 Noha Alaa, PharmD, PhD 24 Radionuclides Penetrating *Alpha power *Beta – *Beta + *Isomeric transition (gamma rays) https://www.youtube.com/ Uses Half-life watch?v=vSwlyzVWUsc (from 0:57-3:42 minutes only) Radiopharmaceutical Noha Alaa, PharmD, PhD 25  99mTchas suitable physical & chemical properties for imaging purposes:  It has a 6-hour half-life (t1/2); long enough to allow imaging to take place in the working day, & short enough that patients are not radioactive for long periods (in 24hrs, PRINCIPLES OF or 4 half-lives, the radioactivity will decay by 94%). 99MTC-  By purchasing 99Mo/99mTc generator, 99mTc can be RADIOPHARMACEUTICAL readily available to the hospital site in a sterile & PRODUCTION pyrogen-free form.  99mTc has a versatile coordination chemistry and will allow a large number of ligands to complex with it, so a wide range of radiopharmaceuticals can be prepared & provided for the many different investigations carried out in nuclear medicine departments. Noha Alaa, PharmD, PhD 26 Radiopharmaceutical Organ or tissue of distribution Main clinical application Imaging the thyroid gland & ectopic Thyroid tissue 99mTc-sodium pertechnetate Dynamic images of accumulation & Salivary gland drainage to show gland function 99mTc-macro- Lung perfusion studies most aggregates of albumin Lung blood flow commonly for the diagnosis of (MAA) pulmonary embolism 99mTc-sestamibi Heart Cardiac perfusion imaging 99mTc-mercapto Dynamic studies to study kidney Kidney triglycine (MAG 3) function 99mTc-dimercapto- Static imaging showing the kidney Kidney succinic acid (DMSA) Noha Alaa, PharmD, PhD structure 27   Radionuclides with long half-lives (ex. 131I, t1/2 = 8 days) can be easily transported from production site to the user hospital.  However, for shorter half-life radionuclides (99mTc, t1/2 = 6hrs), a radionuclide generator is used The to provide 99mTc to the hospital site. production of  Radionuclide generators work on the principle 99mTc that they contain a relatively long-lived ‘parent’ radionuclide that decays to produce a ‘daughter’ radionuclide.  The chemical nature of parent & daughter is different, allowing separation of the daughter from the parent. Noha Alaa, PharmD, PhD 28 The molybdenum/technetium generator consists of 99Mo (long-lived ‘parent’) absorbed onto an alumina-filled column, the 99Mo being present in the form of molybdate (99MoO42-). 99Mo decays to its ‘daughter’ radionuclide 99mTc, as pertechnetate, 99mTcO4-. By drawing a solution of sodium chloride 0.9% through the column, 99mTc is removed from the column in the form of sodium pertechnetate, Na99mTcO4. Noha Alaa, PharmD, PhD 29   Elution of the generator is repeated daily to provide the radiopharmacy with a supply of 99mTcO4 for 7-14 days after that 99mTc becomes too small to be useful. The molybdenum/ The sterility of the eluates is maintained by using: technetium  Sterile sodium chloride 0.9% generator  0.22μm filter through which air enter the system  A terminal eluate 0.22μm filter for the final solution Noha Alaa, PharmD, PhD 30   Commercially available kits are used to manufacture these radiopharmaceuticals.  These kits allow the radiopharmacist, in the hospital environment, to transform the pertechnetate, via complex chemical reactions performed within the vial, PREPARATION OF 99MTC- into the desired radiopharmaceutical. RADIOPHARMACEUTICALS  This is achieved by the simple addition of pertechnetate into the vial followed by shaking to dissolve the contents.  These ligands form a complex with 99mTc to be targeted to special organs to allow the imaging of these organs. Noha Alaa, PharmD, PhD 31   Radionuclides with short half-lives require their preparation & administration on the same day. FACILITIES  Because of the thermal lability of some of these REQUIRED FOR products, it is not possible to use terminal THE sterilization by autoclaving & hence these injections must be prepared using aseptic PRODUCTION techniques. OF RADIOPHARMACEUTICALS  Highly skilled operators work with sterile ingredients within clean room facilities containing either laminar flow safety cabinets or isolators. Noha Alaa, PharmD, PhD 32   Shielding:  Plastic, Perspex & metals of low molecular weight such as aluminium are appropriate materials for RADIATION shielding beta-emitters. PROTECTION IN  For gamma emitters, high molecular weight THE metals such as lead & tungsten should be used. RADIOPHARMACY  The thickness of shielding material necessary for gamma emitters is dependent on the gamma-ray energy – the greater the energy, the thicker the shield required.  All vials containing radioactive material would be contained in a 3mm lead pot. Noha Alaa, PharmD, PhD 33  Sharps Container Shields  The syringes, during the operation, should also be contained within a syringe shield, which is made of materials such as lead, tungsten, lead RADIATION glass or lead acrylic, the latter two being PROTECTION IN transparent. THE  Handling the vials outside their lead pots should RADIOPHARMACY be carried out using long forceps & not with the fingers. High Density Lead Glass Vial Shield Noha Alaa, PharmD, PhD 34   Distance: increase the distance for more protection, by doubling the distance the radiation dose is quartered.  Time: Minimizing the time spent handling a radioactive source will reduce the radiation dose. RADIATION  The staff working in the radiopharmacy will be PROTECTION IN constantly monitored to access their radiation exposure THE & to ensure compliance with safety legislation. RADIOPHARMACY  Whole-body dose may be monitored with film badges & the radiation dose to the finger pulp with thermos luminescent dosimeters.  https://www.youtube.com/watch?v=pzqJN14BKiU Noha Alaa, PharmD, PhD 35   Sewell GJ. Specialized services. In: Winfield AJ, Richards RME. Pharmaceutical Practice, 3rd ed, Churchill Livingstone, London, UK; 2004: Chapter 42.  Shaw SM, Ponto JA. Nuclear Pharmacy Practice. In: Beringer P, DerMarderosian A, Felton L, et al. References Remington, The science and practice of pharmacy, 21st ed., Lippincott Williams and Wilkins, Maryland, USA; 2006: Chapter 106.  World Health Organization (WHO), Radiopharmaceuticals, Final text for addition to The International Pharmacopoeia (November 2008). Noha Alaa, PharmD, PhD 36 Noha Alaa, PharmD, PhD 37