Radiopharmaceuticals in Nuclear Medicine

Radiopharmaceuticals

• Radiopharmaceuticals consist of radioactive isotopes combined with active molecules.
• These specialized drugs are primarily used in nuclear medicine for diagnostic and therapeutic purposes.
• Targeted imaging or treatment of specific tissues or organs is enabled through the emission of detectable radiation, as used in PET scans.
• Compared to other procedures, it offers non-invasive, precise diagnosis and treatment with minimal side effects.
• The ability to detect and treat diseases at early stages has been revolutionized using controlled radiation exposure.
• Formulations consist of radioactive substances, radioisotopes, and molecules labeled with radioisotopes.
• Used for diagnosis or/and therapy.
• The use of these materials requires careful handling by trained personnel in approved facilities, following guidelines from the Atomic Energy Regulatory Board (AERB) of India.
• Radiopharmaceuticals are essential components of nuclear medicine practice, used for diagnosing, managing, and treating various diseases.
• Approximately 95% of radiopharmaceuticals are for diagnostic purposes, while the remainder is for therapy.

Isotopes

• Isotopes are variants of an element differing in neutron number, consequently affecting nucleon number.
• Isotopes of an element share the same number of protons but differ in the number of neutrons.
• Isotopes of an element are atoms of the same element; they have the same atomic number 'Z' but different mass numbers 'A'.
• They occupy the same position in the periodic table and display similar chemical properties.

Units of Radioactivity

• Curie (Ci) was the original unit of radioactivity, named after Marie and Pierre Curie.
• One Curie equals the number of disintegrations from 1 gram of Radium-226, equivalent to 3.7 x 10^10 Becquerels (Bq).
• Becquerel (Bq), the SI unit of radioactivity, represents one nuclear transmutation per second.
• The activity of a radioactive source is defined as the number of transformations per unit time.
• The old traditional unit of radiation is the curie (Ci): one curie is 3.7×10¹⁰ disintegrations per second (dps).
• The SI unit is becquerel (Bq), equal to 1 dps and a metric unit.

Measurement of Radioactivity

• Measuring nuclear radiation is critical for identifying radiation types (α, β, γ) and assessing radionuclides that emit radiation.
• Identification is based on the properties of the radiation, and requires suitable detectors.
• Ionization is measured using Ionization Chambers, Proportional Counters, and Geiger Muller Counters.
• Scintillation detectors are used to measure the scintillation effect of radiation, while Autoradiography measures the photographic impact.

Gas Filled Detectors:

• Different kinds exist, including Ionization Chambers, Proportional Counters, and Geiger-Muller Counters.
• Ionization chambers are the simplest type, collecting all charges created from direct ionization of gas molecules via an electric field application.

Proportional Counters

• A modified type of ionization chamber that operates at high voltage (1000-2000v).
• Designed to detect charged particles with lower ionization power, including beta and gamma particles.
• Filling gas is 90% Argon and 10% methane; the primary ion produces particles that collide and produce secondary ions and give rise to a detector pulse.
• Detects low-energy particles, it has high ionization power.
• A high degree of stable voltage is a disadvantage, as slight voltage voltage changes can affect gas multiplication.

Geiger-Muller Counter

• The GM counter was developed by Geiger and Muller in Germany in 1928.
• It detects and measures ionizing radiation, including alpha, beta, and gamma radiation.
• It is the oldest and most commonly used radiation detector due to its simplicity, low cost, and ease of operation.
• GM tube-based sensing element, which detects radiation and processes electronics to display results.
• The GM tube has an inert gas like Helium, Neon, or Argon at low pressure, with a high voltage of 400-500 V applied.
• The electrical charge conducts when a particle or photon of radiation makes the gas conductive by ionization, and the electrical charge produces an easily measured detection pulse.
• Cylinder is 1-2 cm of stainless steel or glass coated with silver on the inner side to act as the cathode.
• Contains an internal tungsten wire is suspended which is mounted at one end with a glass bead to act as an anode.
• The cylinder contains a gas mixture, e.g argon and helium, with a small amount of quenching vapor.
• Radiation passes through a thin window, ionizing gas molecules.
• Electrons are ejected from the ionized atoms.
• With high voltage across electrodes (300-1300V), electrons and ions move towards anode and cathode.
• Radiations produce a brief current pulse via a radioactive sensor, recorded by computer.
• The GM counter pulses have the same amplitude, regardless of the incident radiation type.
• A GM counter cannot distinguish type of radiation or energy, but the multiplication factor is a big advantage.
• Comes in end-window and window-less types.
• Quenching vapors are used to prevent pulses due to positive ions reaching the cathode and to absorb photons emitted by atoms/molecules returning to the ground state.
• Counters for radioactive gases use lead or copper cathodes.

Scintillation Detector

• High-energy radiation or photons striking certain substances result in light emission, which is called fluorescence or phosphorescence.
• The output light measures adsorbed radiation on the scintillation detector.
• The emitted light multiplies and amplifies signals in the photomultiplier tube, measuring alpha, beta, or gamma radiation using scintillation.
• Common inorganic scintillation detectors are alkyl halides, including Sodium iodide, Cesium iodide and Lithium iodide.
• Organic scintillators like plastic scintillators and have good scintillation properties, but stilbene has low scintillation rates.

Semiconductor Detector

• A diode of n (electron rich) and p (electron deficient) semiconductors.
• Has a band gap of 2-3 eV resulting in a high degree of resolution when detecting radiation.
• Absorption of radiation results in electron and hole pairs moving under the influence of an electric field.
• Electrons are collected at the electrode to produce a voltage pulse.
• The intensity of the voltage pulse produced is proportional to the the electrode is proportional to the incident radiation level.

Solid State Detector

• Provides high resolution, compactness, and easy interpretation of output signal.
• Cerenkor Detectors use light emitted by fast-charged particles through an optically transparent medium with a refractive index of more than one.
• Thermoluminescence dosimeters use inorganic crystals that trap pairs and lead to light emission when heated; examples include CaSO4:Mn, LiF, CaF2:Mn, etc.
• Track-etch Detector utilizes ionizing radiations to create trails of damaged molecules in dielectric material.

Autoradiography

• A bioanalytical technique used to visualize a radiolabeled substance using radioisotopes.
• Radioisotopes emit ionized radiation to form a dark spot in a photographic emulsion; the common example is Silver halide (Ag x) + Gelatin.
• The process follows the equation Agx → Ag + X.
• The method involves covering a radioactive sample with a photographic emulsion, with the result as a dark colored band.
• The slide is washed to get isoluble silver atom, and observe under the autoradiogram.

Properties of Alpha, Beta, and Gamma Radiations.

• All substances are made of atoms. These have electrons (e) around the outside, and a nucleus in the middle.
• The nucleus consists of protons (p) and neutrons (n), and is extremely small. (Atoms are almost entirely made of empty space!).
• The nucleus is unstable and experiences radioactive decay.

Alpha Particles

• Made of 2 neutrons and 2 protons, affected by both electric and magnetic fields.
• Speeds average of 10% of the speed of light, depending on the source.
• Alpha particles do not easily penetrate.
• Harmless if the source is not close.
• Can be extremely dangerous if they are close to sensitive organs.

Beta Particles

• Consists of fast-moving electrons, positive or negative.
• Depends on source. They can be up to 90% of speed of light.
• Reach up to 1 meter.
• Penetrate aluminum or perspex
• Can to be dangerous when ingested.

Gamma Radiation

• Short electromagnetic energy.
• Speed of light= 3 x 10(8) m/s
• Requires 30 mm lead to stop the
• Does not consist of charged particles.
• Difficult to stop.
• Can be dangerous if not far.
• Can be dangerous if inhaled or ingested.

Half-Life (t1/2)

• The time required to for a radioactive substance to disintegrate a required one-half of its original amount.
• 50% only of radioactive remain unchanged.
• After 2T = 25%, after 3T = 12.5%, at end of 4T = 6.25%.
• end of 107 = only 0.1%.

Sodium Iodide (I131)

• Also known as radiocative iodine.
• I131 is used as an aqueaous solution of sodium iodide.
• Contains less than 90%, but more than 110% of iodine.
• The isotope has been being used since 1942.
• I-131 is prepared in nuclear reactor by neutron-irradiation of a natural Tellurium target.
• Converted into Xenon-131 for 80 days.

Properties of Sodium Iodide (I131)

• It froms a colorless souteion.
• The half lif eis i 8.4.
• Beta + Gamma radiation are being enitted.
• The solution has pH of approximately 7-10.
• A Geiger-Muller (GM) counter or a scintillation detector are used for radiation detection.

Storage and handling of radioactive materials

• Follow these precaustions for safety: Use forceps to avoid touching; prevent food contamination; use protection gear; shield the container; supervise the container area.

Storage of Radioactive Substances

• Keep radiopharmaceuticals in closed containers.
• The conditions should reduce the acceptable level or radiation.
• You should take ionizing radiation into account.
• Preparations for parental should come in glass and be sufficiently transparent.

Precautions for handling radioactive substances

• They are based on the Code of Practice for Handling Radioactive Substances.
• Some of the radioactive substances used should comply with the following characteristics:
  • Radiotoxicity must be as low as possible.
  • Short-living isotopes are preferred to long-living ones.
  • The amounts used must be kept to a minimum.
• Never work alone, especially not outside normal working hours.
• Follow these precautions: separating activities; following area limits; applying radiation; using protective clothing; weearing gloves and cleaning up paper instead; wear shoe covers; do not bring in personal items.
• Return solutions to appropriate shields and storage.

Labelling Radioactive Substances

Labels for radioactive substances must state: radioactive product name, where it is appropriate, the route, quantity, expirey date, any special requirements based on temperature.

Pharmaceutical application of radioactive substances

• Radioactives can have applications, but many of them are used to treat cancer at tumors.
• Americium 24 is antineoplastic.
• Cobalt and and Gold have antineoplastics.

Pharmaceutical Application of Radioactive Substances

• Treatment of Thyroid Disease with Iodine 131 for hyperthyroidism.
• The drug can treat graves disease or toxic diseases.
• Palliative Treat bone Metastasis
• Samarium and isatores and have radiation affect are used.

Treatment of Arthritis

• Diagnostic Radiopharmaceuticals are used for pain in joints.
• Ammonia N 13 Inhection used for coronary disease.
• Holmium can be used of liver tumors.
• Chromium 51 and lodone 125 can evaluate the filtration rate of kidneys.