Radiopharmaceuticals Questions PDF

Radiopharmaceutical Kinetics and Pharmacy Practice Concerns  Homework This chapter can be found in Ansel, 16th edition. Pharmaceutical Calculations, Chapter 21 Will be in D2L quiz section Will be fill-in-the blank on the exam. The math question ar...

Radiopharmaceutical Kinetics and Pharmacy Practice Concerns  Homework This chapter can be found in Ansel, 16th edition. Pharmaceutical Calculations, Chapter 21 Will be in D2L quiz section Will be fill-in-the blank on the exam. The math question are worth more points on the exam. No equations are provided on the exam. Objectives Mostly calculations based. Understand what blocks alpha, beta, gamma radiation Understand what the effective, physical, and biological half-life is and how to distinguish between them. A radiopharmaceutical is an agent that is used for diagnostic or therapeutic procedures. To be safe for human use, it must satisfy the requirements of: the State Board of Pharmacy, the Food and Drug Administration (FDA) and the Nuclear Regulatory Commission (NRC).  Radioactivity Is the natural property of certain nuclides to spontaneously emit energy, in the form of ionizing radiation, in an attempt to become more stable.  Radiopharmaceuticals High-energy radiation produced by decay 1) detected by crystals in camera to create images (IMAGING) OR 2) Cause ionization of molecules in tissue, causing damage (THERAPY) Historical Background for Medical Imaging Early on: STRUCTURE ↔ FUNCTION BASIS OF MEDICAL BUT NOT FULLY DEVELOPED UNTIL EARLY IN 20th CENTURY WITH IMAGING + LAB ANALYSES  Origin of Imaging DISCOVERY OF x-RAYS  November 8, 1895 By Wilhelm Conrad Roentgen. Awarded Nobel Prize in Physics in 1901 (first). Very rapid application as an aid medical diagnosis (e.g. from 1896 to 1901 some 8000 x-ray pictures were taken at Mass Gen Hospital on 3000 patients). It helped to establish organ structure↔function relationship in disease and aid in diagnosis. NOTE: Radiographic images are generated by passing radiation thru a patient to produce an image This is the Very First X-Ray Picture! It is of Wilhelm Conrad Roentgen wife’s hand And an x-ray of a hand today.  Types of Radiation 1. Alpha: unable to penetrate the outer layers of skin or a piece of paper. However, because it has a large charge; it causes damage to the immediate area by breaking down DNA 2. Beta: they have a range of 100 feet in the air and 1 mm in tissue. Can be used therapeutically. (Has medium penetrability; can be shielded with plexiglass) 3. Gamma: has a short wavelength and high energy, thus, high penetrating ability. Can only be shielded by lead. Either way, they should deposit in the target organ in order to be effective! Half-life: the amount of time it takes for one-half of the radioactive atoms present to disintegrate or decay. *You do not need to memorize the half-lives*  Protective Equipment Coats/jackets, aprons, gowns Head/face hand and arm coverings (gloves, etc) Safety Googles Mask or respirator (*Sometimes: depends on what your doing) Self monitoring when done 125I has a 60 day half life, what happens if you get it on your shoes? As Low As Reasonably Achievable (ALARA)  Monitoring Film badge, ring dosimeter, pocket dosimeter; sometimes bioassays  Units of Radioactivity Curie (Ci): means a radioisotope disintegrate 3.7 x 1010 billion atoms per second Millicure (mCi): one thousandth of a curie Microcure (µCi): one millionth of a curie Nanocure (nCi): one billionth of a curie The international unit for radioactivity is the becquerel (Bq); defined as 1 disintegration per second. Other units: kilobecquerel [kBq]. Megabecquerel [MBq], gigabecquerel [GBq]. 1 mCi= 37 MBq or 1 nCi=37 Bq USP replaced the curie with becquerel!!!  Nuclear pharmacy, for therapeutic use: the common unit is “gray” and milligray” Gray is the absorbed radiation dose or the measure of deposition of energy in tissue. Whereas, curie and becquerel measures the activity  Dose Related Radiation Effects Effect Dose – Blood count changes – 50 rem – Vomiting (threshold) – 100 rem – Mortality (threshold) – 150 rem – LD50/60* (with minimal – 320-360 rem supportive care) – LD50/60 (with supportive – 480-540 rem medical treatment) – 100% mortality (with best available treatment) – 800 rem Design determinants of physical characteristics of the radioisotope Diagnostic Imaging Therapeutic Effect Half-life short Longer half-lives desirable (hours--just long enough for (days) image scan) Effect on body tissues Ideally none Damage to target tissues (e.g., cancer) Type of radiation to achieve Gamma Beta, gamma clinical indication (Must penetrate tissues) (damage tissues) Decay product Minimal and short-lived activity Minimal and short-lived activity Dose Low (10-9 g) Relatively high  Challenge: Design your radiopharmaceutical Two radioactive isotopes of iodine are available for medical use: one for imaging the thyroid and another for treating it. Based on half-life and the type of radiation they emit, match the radionuclide with the indication (imaging or treatment). Radionuclide Half-life Type of radiation Indication 131I 8 days (long) Beta, gamma ???? 123I 13 hrs (short) gamma ????  Image dynamic physiological processes Preferential organ target – i.e., Iodine and thyroid gland Typically made of two components, the radionuclide and the chemical compound (conjugate) to which it is bound. – Conjugate may deliver radionuclide to target (e.g., Ab) or alter half-life or lipophilicity – Exception: preferential uptake by organ of radionuclide alone (iodine to thyroid) Goal is for no pharmacodynamic or toxicologic effect on organ or body - dosed in extremely small amounts, (i.e., 10-9 g.) High enough energy to detect, but not high enough to damage tissue Effective half life is combo of physical T ½ and bio T ½ Physical half-life: time for half of the radioisotope to radioactively decay Biological half-life: time for half of the radiopharmaceutical to be metabolized or excreted by the body  RADIOISOTOPES IN COMMON USE Technetium 99 – cancer diagnosis (80% of diagnostic imaging) Gallium 67 – tumor, inflammation localizing agent Iodine 131 - thyroid disorders Krypton 81 – very short-lived gas – used for lung ventilation  TARGETED RADIOACTIVE MOABS Molecular targeting therapy has become a relevant therapeutic strategy for cancer Radioimmunoconjugate is composed of monoclonal antibody and radionuclide – synergistic effect of radiation + immuno-mediated cellular toxicity => increased efficacy and minimizing toxicity Main side effect: Myelosuppression – usually reversible – nonhematologic adverse reactions are mild to moderate.  Radioimmunotherapy v. chemotherapy Radioimmunotherapy uses immunoconjugate composed of antibody and radionuclide that shows combined effects of radiation-induced cell death and immune-mediated cellular toxicity. It used to be an experimental treatment procedure, but has become an important therapeutic modality as a novel anti-cancer therapy in clinical oncology  Radiopharmaceutical kit A kit is a prepacked set of sterile ingredients. – Mixture of ligand, reductant, antioxidants, buffers and other components – When mixed with a radioactive isotope, produces the required product. Kits are commercially available and are the preferred method for the production of radiopharmaceuticals, since they are a “closed” system (i.e, neither the ingredients nor the final solution are exposed to the external environment until compounding in pharmacy).  Adverse reactions to radiopharmaceuticals Adverse reactions to radiopharmaceuticals are very rare overall. They can include: dry mouth; (ALLERGY) rash on the neck, arms or chest; urticaria; sore, swollen lips; edema of the face and eyes; dizziness; sweating; nausea and vomiting; headache; and lethargy. Most reactions that are reported have occurred with the use of bone imaging preparations, probably because these are the most frequently used. Calculations: Chapter 21 in the calculations book The time required for a radionuclide to disintegrate to 50% of original activity Can be calculated using a decay equation: N=Noe-λt N is the specific activity at time t (aka # of atoms present at time t) No is the initial activity (aka # of atoms originally present) λ is the decay constant ln(2) T1/2 = λ A and N for A ; the “A” is *Note: most sources replace N with e o o referring to the activity. They mean the same thing  Half-life The disintegration constant of radioisotope is 0.02496 days-1. Calculate the half-life.  Disintegration Constant The half life of 198Au is 2.70 days. Calculate the disintegration constant. ln2 T1/2 = λ  Remaining Activity Over Time A sample of 131I has an initial activity of 30 µCi (1.11 MBq). Its half-life is 8.08 days. Calculate its activity, in microcuries, at the end of exactly 20 days. N=Noe-λt Q. A vial of sodium phosphate P32 solution has a labeled activity of 500 μCi/ ml. How many milliliters of this solution should be administered exactly 10 days after the original assay to provide an activity of 250 μCi? The half life is 14.3 days. N=Noe-λt Q. The original quantity of a radioisotope is given as 100 mCi. If the quantity remaining after 6 days is 75 mCi, calculate the disintegration constant and half-life of the isotope. N=Noe-λt Rewritten as: LN(N/No) = - λt  Counseling Point The biggest counseling point here is actually something extremely minor but critical… When nuclear pharmacy dispenses it and staff comes to pick it up, make sure its in the properly shielded container and placed in the yellow radioactive “box”/container. This helps prevent contamination and spills! Yes, we have seen people try to walk around the hospital with a syringe filled with radioactive material.