Radiopharmaceutical Preparations Part 1 PDF

Inorganic Pharmaceutical Chemistry: Radiopharmaceutical Preparations Nuclear pharmacy is defined as the area of pharmacy dealing with the compounding and dispensing of radioactive material to be used in nuclear medicine. 1- The atomic structure It is fundamental to look at the structure of an...

Inorganic Pharmaceutical Chemistry: Radiopharmaceutical Preparations Nuclear pharmacy is defined as the area of pharmacy dealing with the compounding and dispensing of radioactive material to be used in nuclear medicine. 1- The atomic structure It is fundamental to look at the structure of an atom to understand what radioactivity is. An atom consists of a positively charged nucleus formed from the so-called nucleons, which are surrounded by negatively charged electrons, which may occupy different energy levels. Protons and neutrons form the nucleus. Protons are nucleons with a positive charge and a mass of 1.6726 × 10−24 g. The atomic number (Z) expresses the number of protons. A neutron is a nucleon without a charge and a mass like that of protons. The so-called neutron number (N) describes the total number of neutrons. Neutrons and protons are held together by nuclear binding forces and therefore form the nucleus. The letter A stands for the number of nucleons, which is the sum of number of protons (Z) and neutrons (N). Electrons have a mass of 9.1094 × 10−28 g and they move in energy levels around the nucleus. Lower orbitals, which are defined as orbitals closer to the nucleus, possess higher kinetic energy. If an electron moves to an orbital closer to the nucleus, energy is released, whilst the energy is required to move it away from the nucleus. The number of electrons should be equal to the number of protons to have an element without any charge. Typically, the number of neutrons equals the number of protons. 1 Inorganic Pharmaceutical Chemistry: Radiopharmaceutical Preparations 2- Isotopes Most elements contain a certain percentage of atoms which differ in atomic weight or mass from most of the atoms present. These different forms of an element are known as isotopes, and they vary in the number of neutrons contained in the nuclei of their atoms. Isotopes of a particular element, then, have the same atomic number (same number of protons) but different mass numbers (differing numbers of neutrons). The isotopes of a particular element have the same chemical and physical properties. The only variation that is usually found is in kinetics or rates of chemical reactions involving the isotopes, since the mass is a very important aspect of reaction rates. Another fact about isotopes is that the natural abundance of stable forms in elements is constant regardless of the form in which the element 13 is found. For example, carbon always contains about 1% of C and 99% of 12C. Two major types of isotopes are found in nature. Stable isotopes (nuclides) maintain their elemental integrity, and do not decompose to other isotopic or elemental forms. Unstable or radioactive isotopes (radionuclides), however, decompose or decay, by emission of nuclear particles, into other isotopes of the same or different elements. Not all radioactive isotopes are found naturally in elements. In fact, many unstable isotopes are produced synthetically for their usefulness in chemical, geological, and biological applications. The production of radioactive isotopes usually involves the bombardment of atomic nuclei with subatomic particles, i.e., 2 Inorganic Pharmaceutical Chemistry: Radiopharmaceutical Preparations neutrons or electrons, to produce unstable nuclei of the same or a different element. 3- Radioactive Decay Decay is characteristic of a particular isotope and continues until a stable isotopic level is achieved. Since the transition from one isotope to another, whether it is within the same element or not, involves nuclear transformations, the chemistry of radioactive isotopes differs from the chemistry of stable isotopes by the additional aspect of nuclear reactions. Radiation can take place in the form of α, β−, β+, X-rays and γ-rays. There are two reasons for the occurrence of radioactive decay: First is that the ratio of neutrons to protons is greater or less than 1. The second reason is that radioactive decay takes place because of an energy imbalance within the atom, which means that the atom needs to get rid of energy to reach a stable form. A. Alpha Particles (α, 42He+2) This radiation is by far the heaviest and slowest of all radioactive emissions. The particle is a helium nucleus, containing two protons and two neutrons for an atomic mass of 4 and an atomic number of 2. It is the most highly charged nuclear species, with a charge of +2, giving it a very high ionizing power upon interaction with air or other media. Alpha particles move at a relatively slow speed, averaging about 0.1 the speed of light and their penetrating power is very low. They can be stopped by a sheet of paper or a very thin sheet of aluminum foil. Alpha radiation is usually emitted only from elements having atomic numbers greater than 82. Isotopes emitting alpha particles will decay to the element having a mass number of four less and an atomic number of two less than the original isotope. 3 Inorganic Pharmaceutical Chemistry: Radiopharmaceutical Preparations The emission of alpha radiation is illustrated below with radium-226: ²²⁶₈₈Ra → ²²²₈₆Rn + α (or ⁴₂He⁺²) The low penetrating power of alpha particles makes isotopes emitting this type of radiation rather useless for biological applications because these particles cannot penetrate tissue. In general, interaction of α-radiation with neighboring matter can occur in two ways through ionization or excitation. Excitation means that α-particle can, upon collision, promote an electron to a higher energy level (higher outer shell). Once the electron falls back to its original energy level, energy is emitted. The more important interaction is the ionization of an atom. This occurs when α-particle collides with its target and ‘strips’ away an electron, leaving behind a positively charged molecule. B. Beta Particles (β⁻ or β⁺) This is the terminology normally applied to radiation which may be further described as an electron of nuclear origin. Beta particles are negatively charged species having the mass of an electron. Since this radiation is lighter than alpha particles, they move at faster velocities often approaching 0.9 the speed of light. Their emissions from elements do not alter the atomic mass but do alter the atomic number. Depending upon their energy, beta particles have more penetrating power than alpha particles and are often able to travel from 10 to 15 mm in water or penetrate almost 1-inch thicknesses of aluminum. Their clinical applications include imaging methods as well as therapeutic ones. 4 Inorganic Pharmaceutical Chemistry: Radiopharmaceutical Preparations When the ‘neutron to proton ratio’ is >1, within the nucleus a neutron is converted into a proton and a negatively charged β-particle (negatron, β−). Additionally, a so-called antineutrino (𝜈) is ‘produced’, carrying away any excess binding energy from the nucleus. These processes result in an increase in the proton number (Z) to Z+1 and a decrease in the neutron number (N) to N−1. Negatively charged β- particles have the appearance of electrons, but they originate from the nucleus and carry energy. In contrast, electrons that are present in the orbit outside the nucleus have no energy and obviously their origin differs. An example of beta decay is illustrated with carbon-14: 14 6C → 147N + β− Positron emission is the ejection of positively charged β-particles from a proton- rich nucleus. This occurs when the neutron to proton ratio is