Radiopharmacy

• Personalized and precision medicine approaches

  Employ molecular imaging for patients diagnosis and prognosis
• Radiopharmaceuticals


  Enable molecular imaging
• Radiopharmacies and radiopharmaceutical companies

  Manufacture radiopharmaceuticals and supply them to hospitals, playing a critical role in bringing molecular imaging to patients
• Radiopharmaceuticals


  Used in therapy of cancer, thyroid diseases and other conditions
• Where radiopharmacists work


  • Research organizations which conduct clinical trials of radiopharmaceuticals
  • Hospitals which make their own radiopharmaceuticals
  • Contract Research Organization (CROs)
  • Contract Manufacturing Organizations (CMOs) – centralized radiopharmacies
  • Pharmaceutical and biotechnology companies
  • Private medical practices
• Radioactivity


  A property of atomic nuclei caused by the structural instability of some nuclei, resulting in the spontaneous transformation of unstable nuclei into more stable nuclei, with the emission of excess energy in the form of ionizing radiation
• Radiation


  Energy in motion, in the form of sub-atomic particles (protons, neutrons, alpha particles, beta-particles, positrons) or electromagnetic radiation (gamma rays, X-rays)
• Sub-atomic particles


  • Emitted directly from the nucleus
  • Beta (β) particles: negative electrons (negatrons) or positive electrons (positrons)
  • Alpha (α) particles: +2 Helium nucleus (2p + 2n)
  • Travel only microns (alphas) or millimeters (betas) in any solid or liquid matter including living tissues, used primarily for therapy
• Electromagnetic radiation (photons)


  • Emitted directly from the nucleus
  • Gamma (γ) rays: High energy/more penetrating
  • X-rays: Lower energy/less penetrating
  • Travel >> 1 cm in any solid or liquid matter including living tissues, used primarily for imaging/diagnosis
• 177Lu


  A component of anti-cancer drugs Lutathera and Pluvicto
• Pop Quiz 1


  Iodine has an atomic number of 53. Calculate the neutron number of 131I.
• Pop Quiz 2


  Among the following group of radionuclides, identify those which are isotopes, isotones and isobars: 11 6 C, 10 5 B, 11 5 B, 11 4 Be
• Determinants of nuclear stability

  • Size (atomic number Z)
  • Neutron to proton ratio (N/Z)
• A BFCA has to form metal chelates with high thermodynamic stability or better kinetic inertness at 5 < pH < 7.5
• Alpha (α) decay


  • Occurs only for large nuclei, Z > 90
  • α particles emitted by a particular radionuclide are monoenergetic and have a characteristic kinetic energy
  • α particles typically have kinetic energies of ~ 5 MeV
  • α emission does not alter N/Z ratio. A is decreased by 4 units, N – by 2 units and Z – by 2 units
• Radionuclides


  • 18Fluorine
  • 11Carbon
  • 89Zirconium
  • 111Indium
• 99mTechnetium


  With 6 hr half-life decays via IT to 99Technetium with 10^5 years half-life
• The loss of radiometal would cause undesirable side effects by accumulation in nontarget organs
• Decay constant


  N=N0 e-λt, where N is the number of atoms at time t, N0 is the number of atoms at time 0, and λ is the decay constant for the radionuclide - it is the fraction of the atoms in a sample of that radionuclide undergoing radioactive decay per unit of time
• Branching decays


  e.g. 18F has 97% positron decay and 3% electron capture, so it λ = λ1 + λ2
• Radioactivity


  A= λN, where A is expressed in disintegrations per second (Becquerel (Bq), SI unit)
• Radioactivity


  A=A0 e-λt
• Curie (Ci)


  1 Ci= 3.7 x 1010 Bq
• Half-life


  T1/2 of a radionuclide is the time required for it to decay to 50% of its initial activity level
• Half-life formula


  T1/2 =0.693/λ
• Average lifetime


  τ = 1/λ, τ= 1.44 T1/2
• Specific activity


  Radioactivity of 1 g of the radioisotope, expressed in Bq/g. A=(0.693 x 6.023 x 1023)/(atomic weight of the radioisotope x T1/2), where 6.023 x 1023 is Avogadro's number. This formula should be used only for carrier-free radioisotopes, which do not contain any stable isotopes of the same element.
• Pop up quiz


  Calculate the specific activity of 1 g of 131Iodine with half-life of 8 days.
• Bateman Equations


  Needed when the product of radioactive decay (daughter) is also decaying. Examples: 99Molybdenum -> 99mTechnetium -> 99Technetium, 225Radium -> 225Actinium -> 221Francium -> 213Bismuth -> 209Bismuth.
• Secular equilibrium


  Parent is very long lived, and a daughter is very short lived, e.g. 225Actinium (9.9 days) and its daughter 213Bi (46 min). When A1 = A2, the parent and the daughter are in secular equilibrium.
• Transient equilibrium


  Parent half-life is longer than the daughter's half life, but is not infinite. A2/A1=T1/(T1-T2), tmax = [1.44T1T2/(T1 - T2)]ln(T1/T2). Example: 99Mo/99mTc.
• Pop up quiz


  Calculate the time when the maximum daughter activity is available for 99Mo/99mTc pair with the half-lives of 66 and 6 hours, respectively.
• No equilibrium


  When the daughter's half-life is longer than the parent's half-life, there is no equilibrium between them. Example: 131mTellurium with 30 hr half-life decays to 131Iodine with 8 days half-life.
• Free radiometals may show a high toxicity (177Lu, 90Y, or 153Sm are "bone seekers" and would cause bone marrow damage)
• Approaches to production of radionuclides

  • Traditional: Nuclear reactors
  • Particle accelerators

  Alternative: Photonuclear reactions

  • Spallation sources
• The BFC is often competing with natural chelators present in the blood stream like transferrin or serum albumin
• Research Nuclear Reactors Worldwide and in Canada

  • Chalk River Reactor at the Canadian Nuclear Laboratories (Ontario) – decommissioned
  • McMaster Nuclear Reactor (Ontario)
  • École Polytechnique (SLOWPOKE-2) (Quebec)
  • Saskatchewan Research Council (SLOWPOKE-2) - decommissioned
  • Royal Military College of Canada (SLOWPOKE-2) (Ontario)
• Neutron flux


  The most important characteristic of a research nuclear reactor, measured in neutrons/cm2 x sec. To obtain radionuclides usable for radiopharmaceutical production, neutron flux needs to be > 10^13. McMaster Nuclear Reactor neutron flux is 10^14 neutrons/cm2 x sec
• New way to produce radionuclides in commercial nuclear power plant reactors

  1. New Isotope Production System at Bruce Power successfully produces first medical isotope

  2. First-of-a-kind Isotope Production System continues to progress towards commercial, industrial-scale production of medical isotopes for cancer therapeutics
• An international collaboration between Bruce Power, Isogen, and ITM Isotope Technologies Munich SE (ITM), announced today a milestone marking the first instance lutetium-177, a short-lived medical isotope, has been produced in a commercial nuclear power reactor.