Glossary: Definitions and Terminology

Active Pharmaceutical Ingredient (API) refers Becquerel (Bq) is the unit of radioactivity. to a substance or substance combination that is One becquerel is equal to 1 disintegration per used as an active substance or excipient for the second. preparation of radiopharmaceuticals for human Biological Half-Life is the time required for use. It may be used as such or as a starting half the radioactive material to be excreted by material for subsequent formulation to prepare the body by natural processes. radiopharmaceutical. API also refers to the Carrier-Free (CF) refers to radionuclides hav- active or central ingredient in the radiopharma- ing maximum theoretical specific activity val- ceutical which causes the direct effect for diag- ues when all the atoms contain one isotope of nosis or treatment. the element. Carrier-free thus denotes a radio- Antibody (Ab) is an immunoglobulin mol- nuclide having 100 % isotopic abundance, i.e., ecule that is produced in response to an anti- free from any stable isotopes. gen and forms a specific complex with it. By Chelating Agent is a compound whose mol- becoming attached to antigens on infectious ecules can form several coordinate covalent organisms, antibodies can render them harm- bonds to a single metal ion. less or cause them to be destroyed. Chemical Purity is defined as the fraction of Aseptic Technique consists of a set of scrupu- the chemical of interest in the specified chem- lous specific practices or rules and procedures ical form. It is the measure of the degree to conducted under controlled conditions to pro- which a chemical substance is undiluted or hibit or minimize the chance of contamination. unmixed with extraneous material. In mono- It is adopted during the preparation of radio- graphs, radiopharmaceutical preparation pharmaceuticals to maximize and maintain chemical purity is controlled by specifying asepsis, the absence of pathogenic organisms. limit on chemical impurities. Bacterial Endotoxin (BET) Test is used to Clean Room is a controlled environment, detect or quantify any endotoxins which may typically used for the production of radio- be present from gram-negative bacteria using pharmaceuticals, where concentration of amebocyte lysate from the horseshoe crab dust, airborne microbes, aerosol particles, and (Limulus polyphemus or Tachypleus tridenta- chemical vapors are controlled to specified tus). Endotoxins are only permitted at very low very low limits. levels because of high fevers which they cause. Cold Kits are freeze-dried injectable sub- Batch is defined as the quantity radiopharma- strates ready for radioisotopic labeling which ceutical or radiochemical obtained in one pro- do not need refrigeration, which are prepared duction. The units are often expressed either by lyophilization. They can be stored at ambi- in mass (mg or gram), volume (mL or L), total ent temperatures, have a long shelf life, and radioactivity (Ci or GBq), or total number of can be completely instantly reconstituted with vials or doses. radioactive solution.

Critical Organ is also referred to as the physi- activity readout is based on the ionization cur- ological system that is functionally essential rent measured as photons emitted by a radioac- for the body and would receive the highest tive source that interacts with the gas in a sealed, radiation dose from a radioactive material gas-filled ionization chamber which has a conve- after administration of radioactivity. nient shape and capacity for various-size vials, Curie (Ci) is the unit of radioactivity that syringes, and other containers. is defined as 3.7 × 1010 disintegrations per Kit for Radiopharmaceutical Preparation is second. a set of nonradioactive reagents which are Dispensing is the process of aliquoting bulk reconstituted and/or combined with a radio- radioactive solution into unit dose forms, sub- nuclide following the protocol suggested by ject to release before medical administration. the manufacturer for preparing the final radio- Dosage is a general term for the activity level pharmaceutical formulations or radiolabeled of a radiopharmaceutical administered, gener- derivative which then allows it to be easily ally defined in millicurie (mCi) or millibec- administered to the patient for diagnosis or querel units (mBq). therapy. Such kits are also often referred to as Freeze Drying (Lyophilization) is a drying “cold kits,” as they are devoid of radioactivity. process in which water is sublimed from a Labeled Compound is a chemical compound product after it is frozen and placed under a in which part of the molecules are labeled vacuum allowing the ice to change directly with a radionuclide or radioisotope. The from solid to vapor without passing through radionuclide is as an integral component of a liquid phase. This drying process is appli- the molecule. cable for the manufacture of certain pharma- No Carrier Added (NCA) radionuclide is ceuticals and biologicals that are thermolabile characterized as no carrier added (NCA or or otherwise unstable in aqueous solution for n.c.a.) in which no carrier atoms have been prolonged storage periods, but that are stable added and for which precautions have been in the dry state. taken to minimize contamination with stable

Half-Life (t½) is the time required for one half isotopes of the element in question. It does not quantity of a radionuclide to decay to half its necessarily mean, however, 100 % isotopic initial value. It is a unique characteristic of a abundance. radionuclide and related to the decay constant Nuclide (from nucleus) is the specific consti- (λ) by t½ = 0.693/λ. tution of an atom characterized by its mass Hot Cells are shielded nuclear radiation con- number “A,” its atomic number “Z,” and by its tainment chambers equipped with remote nuclear energy state. handling accessories designed to control and Parenteral is a term indicating the drug manipulate the equipment during the radio- administration route other than oral intake. isotope processing and during preparation and Parenteral radiopharmaceutical dosage forms dispensing of radiopharmaceuticals. are intended for administration as an injec- Isotope is an element with similar chemical make- tion or infusion. Common injection routes are up and the same atomic number, but different intravenous (into a vein), subcutaneous (under atomic weights to another or others. The atoms the skin), and intramuscular (into muscle). of isotopes have the same number of protons in Infusions typically are given by the intrave- the nucleus, but different number of neutrons. nous route. Isotopic Carrier is a stable isotope of the ele- Radiopharmaceutical is any radioactive phar- ment either present or added to the radioiso- maceutical or compound in a form suitable for tope of the same element. It differs only in administration to humans for diagnostic imag- isotopic composition from the radioisotope ing or therapy. with which it is mixed and dilutes the SA. Radiopharmaceutical Precursor is a chemi- Isotope Dose Calibrator is an instrument used for cal compound or ligand used as a starting the activity measurements of radiopharmaceuticals material for the radiolabeling process for administered in nuclear medicine. The displayed preparation of the radiopharmaceuticals. It Glossary: Definitions and Terminology 347

could either be an inactive chemical com- Radionuclide Precursor is any radionuclide pound, API, or a radiolabeled intermediate produced for the radiolabeling of another sub- produced for the preparation of radiopharma- stance prior to patient administration. ceutical formulation prior to administration. Radionuclidic Purity is defined as the fraction Radioactivity is defined as the spontaneous emis- of the radioactivity of the desired radionuclide sion of particles (alpha, beta, neutron) or radia- to the total radioactivity of the stated radionu- tion (gamma, K capture), or both at the same clide. Any extraneous radioactivity is consid- time, from the decay of an unstable nuclide. ered as an impurity. Radioactive Concentration (RAC) refers to Specific Activity (SA) is defined as the activ- the number of nuclear disintegrations per unit ity of a radionuclide divided by the mass time (the radioactivity) of a radionuclide per (or molar amount) of the sum of all radioac- unit volume of the radioactive preparation. tive and stable nuclides (present in the same Radiochemical Purity is defined as the frac- chemical and physical form) isotopic with the tion of radioactivity of the radionuclide of element involved. Effective specific activity is interest in the desired chemical form to the used to describe the mass or molar quantity of total radioactivity of that radionuclide present a single species radiotracer relative to the total in the preparation. mass or molar quantity of the radiotracer and Radiolysis is a process by which radiolabeled nonradioactive compound(s) that has similar compounds or radiopharmaceuticals are biochemical properties. Units are often mCi/ unstable in a radiation field and decompose. mg, Ci/gm, etc. Radionuclide is an unstable form of a nuclide Sterility specifies the absence of any viable that is radioactive and decays by the emis- bacteria or microorganism in a radiopharma- sion of nuclear radiation (alpha, beta, gamma, ceutical preparation. All radiopharmaceuticals neutron, or K capture) to attain stability. The for human administration must be sterilized initial unstable nuclide is referred to as the by suitable means. “parent radionuclide” and the nuclide after Total Radioactivity is defined as the frac- transformation as the “daughter nuclide.” tion of the radioactivity of the radionuclide Radionuclide Generator is a self-contained per unit volume of the dispensed formulation system housing an equilibrium mixture of (vial, capsule, ampoule, generator, etc). It con- a parent–daughter radionuclide pair and stitutes an important parameter in dispensing designed to specifically remove the daugh- and patient administration of radiopharmaceu- ter radionuclide formed by the decay of a ticals as well as from regulatory requirements parent radionuclide which is free from the for the safe handling of radiopharmaceuticals parent. in a radiopharmacy and hospital setting.