radiopharmacy Flashcards
what is a radiopharmaceutical?
A dosage form consisting of radioactive
compound used for either the diagnosis or
therapeutic treatment of human diseases
how are the atomic number and the number of neutrons properties of radionuclides?
• Unstable nuclides
– N/Z ratio away from stable isotopes
– Z ≥83
how do radionuclides decay?
emits particles and/ or energy- this gives a more stable nuclide
what are the forms in which it can emit particles?
– Alpha (or 4He) – Beta (- or e-) – Positron (+) – Neutrons (n) – Gamma ()
what are the properties of an alpha decay emission?(a or 4He nucleus)
– 2 + charge, high energy and limited penetration range (~10-6 cm)
what are the properties of a beta decay emission?
– Various energy, random motion, negative charge
– “neutron rich”
e.g. 13153 I > 13154Xe + B- + u
what are the properties of a gamma ray decay?
– No mass, photon energy, high penetration range
– Isomeric transition
what are the properties of a positron decay emission?
– Positive charge; various energy, random motion
– Proton rich
– Annihilation (2 x 511 keV ~180°)
what are the properties of neutrons decay emission?
no charge, loss of mass
what kind of phenomenon is a radioactive decay?
Radioactive decay is a statistical phenomenon
what is the equation for the radioactive decay?
-dn/dt = a N
where dn/dt = disintegrating rate
a= decay constant; N = no. of radionuclides
why would we integrate the formula for radioactive decay?
Nt = Noe^-at
• where No= no. of radionuclide at time = 0;
Nt = no. of radionuclide at time = t
what is the equation for activity (A)?
Radioactivity of nuclide where At = Aoe^-at
what is the equation for exponential decay?
ln At = In Ao - at
what is the physical half life?
tp= Time required to reduce the initial disintegrating rate
or activity to one-half•
what is the equation for the physical half life?=outside the body
tp= ln2/ap , where 2- 0.693
what is the biological half life?
Time needed for half of the radiopharmaceutical or
radionuclide to disappear from the biological system
what is the equation for the biological half life?
tb=ln2/ab
what is the equation for the effective half life?
1/te=t/tb+1/tp
what are the units of radioactivity?- KNOW HOW TO CONVERT
Curies (Ci)
1 Ci = 3.7 x 1010 dps (disintegrations per sec)
1 mCi = 3.7 x 107 dps
1 uCi = 3.7 x 104 dps
• Bacquerel (Bq) – SI Unit 1 Bq = 1 dps = 2.7 x 10-11 Ci 1 kBq = 103 dps 1 MBq = 106 dps 1 GBq = 109 dps
what is a nuclear reactor?
neurons
– Fission or (n, f) reaction of 235U or 239Pu
– Produce neutron rich radionuclides
what is a cyclotron?
charged particles
– (p,n), (d,n) reactions most common
– Produce proton rich radionuclides
• Expensive production facility → Site produced
• Monoisotropic or enriched source as target form
• Radionuclides with long half life
what is a generator system?
• Radiopharmacy unit in hospital • Portable & reusable system • Lead shield • Radionuclides with short half life • Reasonable half life of parent & daughter*
how is 99MO made?
from 235 fission
what method is mostly used for 99,o-99mtc?
generator
use imaging radionucllide
what are the benefits of using the generator
Simple elution method & reliable separation
what is the solid, solvent phase of the generator method?
Solid phase: alumina column
• Solvent phase: 0.9% saline
is the generator method sterile and pyrogen free?
yes
what forms do the radiopharmaceutical dosage forms come in?
solution, suspension, capsule and gas
what type of container do radiopharmaceutical dosage forms have?
lead
what is an appropriate form for a radiopharmaceutical?
– Ensure radionuclides distribute to target site– Remain stable in vitro & in vivo
what is direct labelling?
e.g. 125I-albumin Injection– Tagging radioisotope with biological molecules– Non-specific binding to antibodies, RBC, etc.
how to you label 99mTC with chelate?
• Oxidation state of Tc
– Tc 7+ to lower values (1+, 3+, 4+, 5+)
– Reducing agents, SnCl2 (stannous chloride) in acid
• Chelating agent
– Coordination donor atoms, e.g. N, O, S, P etc
– Donate lone pair electrons
– Coordinate covalent bond stabilises 99mTc
what makes up the strructure of 99m tc complex?
• Property of complex
– Chelating agent
– Ring size, charge and geometry
– Determine distribution in the body
what is included in a labelling kit?
• No radioisotope • Reducing agent, e.g. SnCl2 • Chelating agent • Antimicrobial, e.g. benzyl alcohol • Antioxidant, e.g. Sodium bisulfite – Avoid re-oxidation of reduced Tc upon Sndepletion • Buffers, acid or base • Solution or lyophilised powder • Separate vials for reconstitution or reaction
how do you assure the quality of a radiopharmaceutical?
• Quality assurance scheme
• Precursor & kit additives and their quality
• Physicochemical tests
-biological tests
what physiochemical tests are availible for quality tests?
– Radioactivity & specific radioactivity
– Radionuclidic species & radionuclidic purity
– Chemical purity for radiopharmaceuticals &
radiochemical purity
– Particle size
– pH
define radionulidic purity
Fraction of total radioactivity in form of the
desired radionuclide present in a
radiopharmaceutical
what do impurities arise from?
– Extraneous nuclear reaction
– Isotope impurities in target materials
what is the specific activity?
Radioactivity per unit mass of a radionuclide or
labelled compounds
what do you account for with specific activity?
Accounted for radioactive and chemical substance
concentrations
– Radioactivity from radionuclide (radionuclidic
purity)*
– Chemical species (radiochemical purity)*
how does specific activity change?
changes with date and time
how do you determine the stability of a radiolabeled product?
• Radiolysis
– Decomposition of radiopharmaceutical by radiation
– Auto-radiolysis & indirect radiolysis
– Absorption of radiation lead to free radical
formation
– e.g. water is irradiated to form H2O2 or HO2. radical
– Depends on specific activity, energy of emitted
radiation & half life
– e.g. Particle emission is more damaging than ray
how does imaging of the thyroid gland work?
Sodium Iodide (131I) or (123I) capsule •Oral route •Monitored uptake •10-35% after 24hr • Hot spot (hyperthyroidism) •Cold spot (carcinoma) • Trapping iodine source in thyroid • Alternative 99mTc Pertechnetate preparation
how does thyroid imaging work?
• Trapping iodine source in thyroid • Alternative 99mTc Pertechnetate preparation
how are radiopharmaceuticals used ar rgerapeutic agents?
• Particle emitters, e.g. , • Ionization energy – Direct and indirect by free radical induction (e.g. R., OH., HOO.) • Permanent damage to DNA via strand cleavage & base pair mutation • Induce cellular apoptosis • Distance from site of action
give examples of radiopharmaceutics for therapeutic use
• Non-Hodgkin’s Lymphoma – 90Y-ibritumomab Tiuxetan(Zevalin®) – Active targeting • Bone metastasis – 32P-Sodium orthophosphate IV – Deposit in the bone • Hyperthyroidism – Excess thyroid hormone activity – NaI( 131I) emit - (90%) & – Active uptake
