Applications of Isotopes in Medicine

Radioactivity, Neutron decay, Proton decay, Scintillation counter, Geiger Muller counter, Radioactive Iodine, Radioactive Iodine, Tritium, Radioactive Phosphorous, PET Scan, Indium, Samarium, Gallium, Technetium, Xenon, Yttrium, Iodine, Thallium

1. Applications of Isotopes in Medicine Pradeep Singh M.Sc. Medical Biochemistry [email protected]

2. Introduction Atomic number (Z): It is the number of protons in the nucleus. Atomic weight/ Mass number (A): It is the total number of nucleons in the nucleus and is equal to protons plus neutrons (P+N). Isotopes: Elements having same Z but different A. Example: 12 C 6 , 13 C 6 , 14 C 6 ; 1 H 1 , 2 H 1 , 3 H 1 ; 125 I 53 , 127 I 55 , 131 I 53. Isobars: Elements having same A but different Z. Example : 40 S, 40 Cl, 40 Ar, 40 K, and 40 Ca . Isotopes can be two types: Stable isotopes : The ratio of neutrons to protons is ~ 1. Radioactive isotopes : The ratio of neutrons to protons is >1.

3. Radioactivity: During spontaneous degradation of nucleus and transformation of an unstable nucleus to a stable form, release of energy or matters occur which is known as radiation. Substitution of an atom in the molecule of a substance by other isotopes of the same element will not alter the chemical properties of the substance whereas isotopic properties will make the substance easily identifiable.

4. Electron was discovered by J.J. Thomson in 1897. Proton was discovered by Ernest Rutherford in 1920. Neutron was discovered by James Chadwick in 1932. Marie Curie and Pierre Curie were awarded N obel P rize in 1903 in physics, f or their study on radiation phenomenon. Fact: Chadwick (the discoverer of neutron) was a student of Rutherford (the discoverer of proton) who was a student of Thomson (the discoverer of electron). History

5. The SI unit of radioactivity is the Becquerel (Bq) and is equal to one disintegration per second (dps). Traditionally radioactivity was measured in Curie (Ci) units. One Curie was defined as the activity of 1gm of radium and later it was expressed as 3.7 X 10 10 dps. 1 Ci = 3.7 X 10 10 dps (or Bq) 1 MBq = 27 μ Ci Units of Radioactivity

6. Radioactive decay is a spontaneous process. Decay constant: The rate of disintegration at any time is proportional to the number of intact atoms (N) of the isotope given by λ is equal to radioactive decay constant. Radioactive decay follows first order kinetics. Half-life, t 1 / 2 = 0.693/ λ   Rate of Radioactivity Decay

7. α-particles are positively charged particles consisting of two neutrons and two protons identical with the nuclei of Helium, 4 He 2 . In order to achieve stability, heavy nuclides decay by emitting α-particles . The emission of α-particles removes two protons and two neutrons resulting in a decrease of atomic number by 2 and mass number by 4 . An example of α-particles decay is as follows : 226 Ra 88 (Radium)  222 Rn 86 (Radon) + 4 He 2 ( α-particle ) Decay by Alpha Particle Emission

8. Both negatively charged electrons β - (negatrons) and positively charged β + (positrons) are recognized as β -particles . Neutron to proton decay: n (neutron)  p (proton) + β - ( negatron) + (anti-neutrino) Example: A X Z  A X Z+1 + β -1 ; 3 H 1  3 He 2 + β - ( negatron) Proton to neutron decay: n (neutron)  p (proton) + β + ( posi tron ) + ν e (neutrino ) Example: A X Z  A X Z+1 + β -1 ; 8 B 5  8 B e 4 + β + ( positron )   Decay by Beta Particle Emission

9. Electron capture is the primary decay mode for isotopes with a relative superabundance of protons (or neutron deficient ) in the nucleus. With insufficient energy difference between the isotope and its prospective daughter (the isobar with one less positive charge) for the nuclide (nucleus) to decay by emitting a positron . Decay by Electron Capture

10. While alpha and beta radiations are particles, gamma radiation is in the form of electromagnetic waves. Gamma rays has no mass and no charge , and therefore penetration power is maximum . Example: 131 I 53 (Iodine)  131 Xe 54 (Xenon) (metastable) ( β - )  131 X 54 ( γ ) In some cases, daughter nucleus resulting from negatron emission, positron emission or electron capture possesses energy excess of its minimum possible ground state energy ( Refer to example ). Such an excited metastable nucleus decays promptly to a more stable nuclear arrangement by emission of γ -rays i.e., electromagnetic waves of very short wavelength. Decay by Gamma Ray Emission

11. Radioactivity is measured as counts per minute (CPM). Two counting techniques in current use are: Scintillation counting Geiger-Muller counting Measurement of Radioactivity

12. Scintillating meaning “ Sparkling ”. Principle: A scintillation counter is an instrument for detecting and measuring ionizing radiation by using the excitation effect of incident radiation on a scintillator material and detecting the resultant light pulses . It consists of a scintillator that generates photons in response to incident radiation, a sensitive photomultiplier tube (PMT) which converts the light to an electrical signal and electronics to process this signal. 1. Scintillation Counting

13. Samples for liquid scintillation counting consist of two components: a. A solvent in which the radioactive substance is suspended. b. Organic Fluorescent substance. This forms liquid scintillation system producing small flashes of light or scintillations which are detected by photomultiplier tubes (PMTs).

14. Scintillation process in detail begins with the collision of emitted β -particles with the solvent molecules. Aromatic solvents, toluene and dioxane are most commonly used as these are easily promoted to the excited state. β + S (Solvent)  S* (Excited state solvent) + β Excited solvent molecules return to the ground state by emission of a photon ( h ν ). S *  S + h ν (photon) The photon (h ν ) emitted are not efficiently detected because of their shorter wavelength. So to overcome this problem, fluorescent substances, i.e., fluors (F1, F2) are added to the scintillation counter. Two widely used primary and secondary fluors are 2,5-Diphenyloxazole (PPO ) with an emission maximum of 380 nm and 1,4-Bis-( 5’-phenyloxazolylbenzene) (POPOP ) with an emission maximum of 420 nm . Scintillation Counting of β -rays

15. Excited solvent molecules (S*) react with F 1 S * + F 1  S + F 1 * (excited fluor) F 1 * (excited fluor )  F 1 + h ν 1 Wavelength of h ν 1 is also short for efficient measurement of PMT so a second fluor, F 2 is added. F 1 * + F 2  F 1 + F 2 * F 2 *  F 2 + h ν 2 h ν 2 is of longer wavelength and efficiently detected by PMT. Pure β -emitters Pure γ -emitters Both β -and γ -emitters 3 H (Tritium) 57 Co (Cobalt) 24 Na (Sodium) 14 C (Carbon) 125 I (Iodine) 131 I (Iodine) 32 P (Phosphorous) 33 P (Phosphorous) 90 S (Sulphur)

16. Both 24 Na and 131 I are both β - and γ -emitters and are often used in biomedical research. A gamma counter is consist of: Sample well NaI (Sodium iodide) crystal as fluor Photomultiplier tubes Sample tube is lowered into the well. The high energy rays are not absorbed by the scintillation solution or vials but interact with a crystal fluor. Gamma ray striking the crystal result in a flash of light that is registered by an adjacent photomultiplier tube. Scintillation Counting of γ -rays

17. It detects ionizing radiation such as alpha particles, beta particles, and gamma rays using the ionization effect produced in a Geiger–Müller tube, which gives its name to the instrument . Unlike scintillation method, these ionization counters rely on detecting the ions produced by fast moving electrons, interacting with the contents of the counter . A typical G-M tube consists of a mica window for entry of β -particles from a radiation source, an anode in the counter of the tube, a cathode surface inside the walls and the cylindrical counter chamber which is filled with argon, helium or neon gas and a quenching (Q) gas, usually butane to reduce continuous ionization of the inert gas . β -particles emitted from high energy of atoms such as 24 Na, 32 P, 40 K have little difficulty in entering the cylinder by penetrating the mica window, whereas particles from weak β -emitter ( 14 C and 3 H) are unable to efficiently pass through the window. So for these modified G-M tubes, thin mylar window called flura window tubes are used. When β -particles pass through a gas they collide with atoms and may cause ejection of an electron from a gas atom resulting in the formation of an ion pair made up of negatively charged electrons and positively charged atom. The positive ions and electrons produced are separated by attraction to a cathode and anode at a potential difference up to a few hundred volts. This leads to extensive ionization . Current generated from electron movement toward the anode is amplified, measured and converted to counts per minute . 2 . Geiger-Muller Counter

18. Counting efficiency of G-M counters is not very high. Response time is longer as compared to photomultiplier tubes. Sample preparation for G-M counters is more time consuming and tedious . Sample is prepared in a metal disc called planchet . Liquid samples are allowed to dry leaving a radioactive residue for counting on the metal disc.The thickness of sample on the planchet is a significant factor. With the increase of thickness of the sample, the process of self absorption of β -particles increasingly becomes a problem. Sample of high radioactivity is not efficiently counted by G- M tube. Disadvantages of G-M Counter

19. To study metabolic pathways: Different isotopes of an element have same chemical properties, these molecules are metabolized by the body similar to normal molecules. Example: 14 C-labeled glucose is used to study the carbohydrate metabolic pathways. 32 P is useful to trace the nucleic acid synthesis in vivo and in vitro. It is used to trace polycythemia. 3 H-labeled thymidine is incorporated in the newly synthesized DNA and therefore used in assessing cell division kinetics. Uptake of 131 Iodine by thyroid gland is used as an index of thyroid function. 131 Iodine is used to treat thyrotoxicosis (excess of thyroid hormone in the body) in case of thyroid cancer or Grave’s disease (autoimmune disorder). 131 Iodine acts by destroying the follicular cells of the thyroid gland . 99m Tc (Technetium) – The most widely used isotope in the world. It is used to study disease processes and observe organ function in many parts of the body including the heart, thyroid, liver, kidneys, gall bladder, lungs, gastric system and skeleton. Every year, Tc-99m is used to diagnose over 40 million people worldwide. Applications of Radioisotopes

20. Positron Emission Tomography (PET) Scan  is an imaging test that helps reveal how your tissues and organs are functioning. A PET scan uses a radioactive drug to show this activity. This scan can sometimes detect disease before it shows up on other imaging tests. Example: 18F-fluorodeoxyglucose ( FDG)  PET is used to determine sites of abnormal glucose metabolism. 90 Y (Yttrium ) – Hope for liver cancer patients. It is of growing significance in liver cancer therapy and is also used to relieve the pain and swelling associated with some types of arthritis. 111 In (Indium) – Targeted Diagnosis. It is used to detect blood clots and locate abscesses and inflammation. It is also useful in diagnosis of certain rare cancers. 153 Sm (Samariu m ) – Cancer Therapy and Pain R elief. It is used to relieve the pain of bone cancers and is an effective treatment for prostate and breast cancer. 201 Tl (Thallium) – Heart Health. It is used to diagnose coronary artery disease, as well as to determine the extent of the disease. It is also useful for locating low grade lymphomas.

21. 67 Ga (Gallium) – Infection Detection. It is taken up and concentrated by tumors and inflammation so it can be used to diagnose even chronic infections. It is also useful for imaging osteomyelitis of the spine. 133 Xe (Xenon) – Breathing Easier. Xenon-133 gas is used to create functional images of pulmonary ventilation. This can advance the treatment of asthma and other respiratory disorders. It also helps with the early diagnosis of certain lung diseases.

22. Thank You!!!