Introduction to Radiopharmaceuticals

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  • Created by: LBCW0502
  • Created on: 27-03-19 15:36
What is a radiopharmaceutical?
A radioactive drug given to a patient for a diagnostic or therapeutic nuclear medicine procedure. Diagnostic >> therapeutic. Imaging >> non-imaging. Planar (2D) >> SPECT (3D) >> PET (3D)
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Outline features of nuclear medicine
A non-invasive diagnostic tool. Provides functional information. Can be extremely sensitive and specific. Requires additional information - clinical history, blood tests etc. Other imaging modalities e.g. X-rays, CT, MRI, ultrasound
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State the features of the multi-disciplinary speciality in nuclear medicine
Patient care (radiographers, technologists, nurses). Medicine (medical doctors, physicians, radiologists, surgeons). Physics (physicists, technologists). Pharmacy (pharmacists, chemists, technicians)
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How are radiopharmaceuticals different from other drugs? (1)
Require shielding of radioactivity. Short shelf-life (minutes to days). Most given via IV. Given in very small amounts (no pharmacological response expected). Strength of every dose can be checked. Purity of every dose can be checked
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How are radiopharmaceuticals different from other drugs? (2)
Released for use without full QC (due to short half life, some basic lab tests carried out)
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Give examples of nuclear medicine studies (1)
Brain/vascular flow (BBB, regional perfusion, transporters, receptors, beta amyloid deposition). Thyroid and parathyroid. Lungs/perfusion (ventilation). Heart/ventricular function (perfusion, infarct). Stomach/transit (bleeding)
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Give examples of nuclear medicine studies (2)
Liver/spleen function (blood volume). Gall bladder. Kidney morphology (filtration, secretion). Bones. Venography. Adrenal - medulla (cortex). Tumours. Infection/inflammation. Lymphatics/flow (sentinel node, lymph-oedema)
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What are the types of radioactive emissions? (1)
Three types of emissions from radioactive isotopes - alpha particles, beta particles, gamma rays (also some associated X-rays). Only gamma rays are useful for radionuclide imaging (high energy photons). Beta/alpha particles used for therapy
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What are the types of radioactive emissions? (2)
In radionuclide imaging, source is inside the body (X-ray CT - source is external)
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What are the types of radioactive emissions? (3)
Alpha emissions cannot pass through tissue (but can be dangerous if the bloodstream is exposed to alpha emissions). Beta emissions pass through tissue but are stopped by perspex. Gamma rays/X-rays pass through tissue and perspex, but stopped by lead
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Describe features of planar gamma scintigraphy (1)
Most commonly used form of radioisotope imaging is planar gamma scintigraphy. Gamma rays are detected external to the body using sodium iodide crystals (dense enough to stop the photons)
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Describe features of planar gamma scintigraphy (2)
Gamma rays pass through a multi-channel lead collimator that cuts out radiation not originating from the area to the imaged
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Describe features of planar gamma scintigraphy (3)
Collimator gives sharp image by accepting only gamma rays aligned with holes. Each gamma ray to converted to green light (one at a time). Sensors to convert green light to an electronic signal (electronics/computer)
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Describe features of planar gamma scintigraphy (4)
Gamma camera components - photo multiplier tubes, detection crystal, collimator. Bad detection (not aligned). Good detection (aligned). Stopped at septa. Image on computer screen, lead housing cameras (protection from gamma rays)
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Describe features of SPECT (1)
Single photon emission computed tomography. 2D planar imaging cannot reveal the depth of the radioisotope within the body. SPECT provides 3D images. Thin slices through the body are reconstructed from planar images acquired over 360 degrees
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Describe features of SPECT (2)
Usually with detectors rotating around the patient. Able to locate masses (e.g. tumours) in 3D space. Dual-headed gamma camera. Tomographic acquisition (3D)
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Outline the basis of PET (1)
Give off a positive electron from atoms. Moves a few mm, meets an electron, cancel out. Small amount of mass, but + and - are directly opposite. When they collide, mass no longer exists, turns into two gamma photons (E = mc^2). Conversion to energy
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Outline the basis of PET (2)
Annihilation. Photons go into equal and opposite directions. Photons hit 180 either side. Cannot use two headed PET camera (poor image). Point where photons cross (hotspot, where drug originated).
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Describe the production of radionucleolides
Nuclear reactor (bombard target with neutrons). Particle accelerator/cyclotron (bombard target with charged particles, protons, deuterons). Generator (parent radionuclide decays to daughter nuclide of medical interest)
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Describe features of a nuclear reactor
Neutron bombardment of target (32-P, 51-Cr, 89-Sr, 125-I). Fission of 235-U, 99-Mo, 131-I. Neutron flux 10^13-10^15. Generally long irradiations. Multiple targets at same time. Expensive to build, operate and decomission
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Describe features of a cyclotron/particle accelerator
Charged particles (protons and deuterons) accelerated in magnetic field. 67-Ga, 111-In, 123-I, 201-Tl, 11-C, 13-N, 15-O, 18-F. Relatively short irradiations. Only one target at a time. Moderately expensive. Table top cyclotron
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What are the two parts of a radiopharmaceutical?
Radionuclide (imaging properties, radiation dose, physical half-life). Drug (localisation, biodistribution/excretion, biological half-life)
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Outline features of localisation mechanisms
Most radiopharmaceuticals are administered systemically (mainly IV, some PO, inhalation, interstitial, intrathecal). Mechanisms range from simple (e.g. particle size, solubility) to complex (receptor, enzyme). Specificity. Location. Target:background
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Outline features of optimal time for imaging
Can range from minutes to days. Rate of specific localisation. Clearance from adjacent organs. Half-life of radionuclide. Dynamic imaging immediately after injection shows blood flow and blood pool
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Describe features of Technetium-99m (1)
Most commonly used radionuclide. Generator produced from 99-Mo (half-life 66h) which decays to 99-Tc with emission of 140 keV gamma-ray. Relatively inexpensive. Suitable for attachment to a variety of compounds. Isomers/isotopes 99m-Tc, 99-Tc
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Describe features of Technetium-99m (2)
Production of 99m-Tc - 99-Mo (t 1/2 66 hours) -> 99m-Tc (t 1/2 6 hours, 140 keV gamma photon) -> 99-Tc (t 1/2 200,000 years)
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Outline features of the generator design (1)
Eluent, tubing, needle, metal closure, glass column, lead shielding, eluate, sterile filter
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Outline features of the generator design (2)
Parent solution added to column. As eluent is added each time, the solution becomes less radioactive and produces a daughter products (eluate). Parent solution more tightly bound to MoO4 complex whereas TeO4 is less tightly bound
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Outline features of the generator design (3)
(Cl- displaces complex within the column)
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State features of the 99-Mo/99-Tc generator yield
Builds up every 24 hours (get maximum yield). Maximum yield decreases over time (fluctuation - graph)
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Describe features of quality assurance of 99-Mo/99m-Tc generator eluate
Radionuclidic purity (99-Mo breakthrough- 0.1%, 1 kBq/MBq, other radionuclides). Chemical purity (alumina breakthrough - 5 micrograms/mL, spot test). Appearance (clear, colourless, free from particles). Lead protection on generator (5 cm length)
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What are radiopharmaceutical kits?
Used to add radioactive element (and saline). Able to make product. Reconstituting vial on the ward. Adding Tc (manufacturing, need procedures in place). Incubation or some products need to be boiled
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State features of the 99m-Tc kit chemistry
TcO4- -(Sn 2+, reducing agent, changes oxidation state) > [TCO] intermediate, less stable - more prone to binding to ligand (Tc-L). But need to protect it from oxygen and water
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What are the components of a 99m-Tc kit?
Drug (carrier/vector/ligand). Reducing agent (usually stannous chloride). Antioxidant (e.g. ascorbic acid, PABA). Intermediate transfer ligand. Buffer/pH adjustment. Surfactant. Bulking agent. Inert atmosphere (N or Ar)
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Describe features of radiochemical purity
Desired radiochemical form as a % of all radiochemicals present. Minimum purity levels set in pharmacopoeias and vary between compounds. Simple RCP testing systems are available for most radiopharmaceuticals
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What are the methods used to determined radiochemical purity? (1)
TLC (standard, instant, paper). High pressure liquid chromatography. Solid phase extraction cartridges (e.g. Sep-Pak). Electrophoresis (separation based on charge, not used much any more except for proteins). Radio-chromatogram scanner/phosphor image
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What are the methods used to determined radiochemical purity? (2)
Radiation detector. Dark spot (equivalent to radiation). Second peak (another dark spot) - e.g. not boiled properly, presence of impurity, generator which was not eluted for a while.
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Describe features of aseptic preparation (1)
Most radiopharmaceuticals are administered by IV injection. Must be prepared under aseptic conditions. Kits and components are sterile. Short half-life, cannot perform stability testing before release
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Describe features of aseptic preparation (2)
Must validate preparation procedures and staff competency. Use of laminar airflow hood and pharmaceutical isolators
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Which radionuclides are used for planar/SPECT?
99m-Tc (t1/2 of 6h). 123-I (t/12 of 13h). 111-In (t1/2 of 67h). 67-Ga (t1/2 of 78h)
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Which radionuclides are used for PET?
11-C (t1/2 of 20 mins). 13-N (t1/2 of 10 mins). 15-O (t1/2 of 2 mins). 18-F (t1/2 of 110 mins)
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What are the challenges in preparation of radiopharmaceuticals?
Radioactivity (protection of operator by shielding or robotic synthesis). Half-life (loss of radioactivity during preparation), requirement for speed. Preparation to pharmaceutical quality (chemically pure, sterile, apyrogenic)
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How are the challenges for radiopharmaceuticals being met? (1)
Planar/SPECT (99m-Tc products prepared from kits, simple/rapid/safe/reliable/high yield), longer lived radionuclides arrive ready to use. PET (automatic synthesis modules, low yields unavoidable, can be distributed within radius of 2-4 h)
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How are the challenges for radiopharmaceuticals being met? (2)
Automated synthesis of 18-F-FDG
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Other cards in this set

Card 2

Front

Outline features of nuclear medicine

Back

A non-invasive diagnostic tool. Provides functional information. Can be extremely sensitive and specific. Requires additional information - clinical history, blood tests etc. Other imaging modalities e.g. X-rays, CT, MRI, ultrasound

Card 3

Front

State the features of the multi-disciplinary speciality in nuclear medicine

Back

Preview of the front of card 3

Card 4

Front

How are radiopharmaceuticals different from other drugs? (1)

Back

Preview of the front of card 4

Card 5

Front

How are radiopharmaceuticals different from other drugs? (2)

Back

Preview of the front of card 5
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