Radiopharmaceutics Flashcards
What is a nuclear medicine
- X-rays show anatomy, but a poor indicator of function
- Nuclear Medicine scans give poor anatomical detail but do show function
- Radiopharmaceuticals are a combination of
- Useful Molecule + Radioactive isotope
Gamma camera
- Gamma photons are emitted by the patient due to medicine/diagnostic agent we injected- this hits the crystal of the camera causing the crystal to scintillate which is picked up by detectors
- Colinator- these are small bits of lead which only allow gamma photons at a certain angle to hit the crystal allowing more accurate imaging (due to photons being given off in random direction)

Low radiation dosage to patients
- Short physical half-life
- Short biological half-life
- Nature of radioactive decay
Philosophy of radiation protection
- All exposures shall be justified
- Benefit gained outweighs risk involved
- All exposures shall be kept as low as reasonably practicable (ALARP)
- We are exposed to radiation at all times- Cosmic radiation, radon gas, buildings, food stuffs
Radiation measurement unit
- A measure of radiation energy in tissue
- Sievert (Sv)
- Use 1/1000 (milliSievert- mSv)
- Or 1/1,000,000 (Micro Sievert- uSv)
- A measure of radiation within the tissue
- Natural radiations
- Average for UK 2.5 mSv per year
Radon- Cornwall

Airline staff

Radiation Effects
- Main concern is carcinogenesis
- Assume a risk, whatever the dose
- Radiation risk
- Taking all factors into account risk of 1 in 15,000 for 2mSv
Radiation effects
- Main concern is carcinogenesis
- Assume a risk, whatever the dose
- Radiation risk
- Taking all factors into account, risk of 1 in 15,000 for 2 mSv
Compare with other risks
- Smoking 10 a day- 1 in 200
- Sea-fishing- 1 in 500
- Mining- 1 in 7,000
- Home accidents- 1 in 10,000
- Road accidents- 1 in 10,000
Limiting Radiation Exposure
- Time- keep to a minimum
- Distance
- Shielding- make sure you use right shield
- SOPs must incorporate
- Staff Training
- Monitoring
- Feedback
Inverse Square Rule
- Distance is very important- it follows a sqaure root rule

Units
- Becquerel- Rate of disintegration (1 d.p.s)
- Says nothing about radiation dose to patients or workers
- Curie in the US- 1 MilliCurie= 37 MBq
- Gray (Gy)- S.I unit of absorbed dose
- 1 joule of energy absorbed per Kg tissue
- Sievert (Sv)- dose equivalent
- Sievert = gray x quality factor (QF)
- For Beta and Gamma emitters, QF =1
Types of radioactive decay
- Alpha (a)
- Beta (B)
- Gamma (G)

Mechanisms of decay
a-particles
- He nucleus- charge +2
- Comparatively large- collide with tissue, give up their energy, cause ion pair (5000 cm-1)
- Considerable damage in small area
- Range in tissue of a few mm
- Can easily be shielded
- NO role in diagnostic agents, but have potential for therapeutic use
B- particles
- Can have negative or positive charge
- Smaller than a-particles- less interaction with tissue (50 ion pairs cm-1)
- Less damage and greater range in tissue
- Range can be up to several cm- depends on energy Emax and Emean
- Valuable for therapy, but not diagnosis
B+ particles
- Known as positrons- antimatter
- Immediately after emission from nucleus, they interact with B- particle
- Annihilation reaction- matter is converted into energy
- B- + B+ => 2 gamma
- Energy of each gamma = 511 keV, emitted at 180o to each other
- Valuable in diagnostic procedures
Gamma rays
- Electromagnetic radiation- not particles
- Less interaction with tissue- hence why good in diagnosis, cause less damage, have greater range in tissue
- Energy of emitted gamma rays constant for a given radionuclide
- Valuable for diagnostic use, especially when radiation can be detected externally
Ideal properties of diagnostic radionuclides
- Gamma ray emission only
- High abundance
- Reduce radiation dose to patient
- For imaging studies, gamma energy 100-250 keV
- High detection efficiency
- No significant body attenuation
- Easy to shield
- Physical half-life approx. 1.5 times duration of test
- Simple cheap and rapid production
- Lack of radionuclidic impurities
- High specific activity
- Rapid production reduces operator dose
- Versatility chemistry- chemically bind it to lots of different molecules
Ideal properties of diagnostic radionuclides
- Chemical quantity- No pharmacological effect
- Radiochemically pure- biodistribution profile
- Chemically stable- doesn’t break down in vivo
- Predictable biodistribution
Technetium- 99m (Tc)
- Metallic element atomic number 43
- Hence 43 protons in the nucleus and 43 electrons
- 20 different isotopes- all radioactive with half-lives of few seconds to millions of years
- Existence predicted by Mendeleev’s periodic table
- First artificially produced in 1937
Technetium- 99m
- The half-life of Technetium- 99m is 6 hours, gamma energy is 140 keV
- Atomic number Mo is 42, Tc is 43, Ru 44
- Principal gamma energies- 99Mo- 740 keV; 99Tcm- 140 keV
- Ruthenium 99 is stable
- Molybdenum and technetium have different chemical properties and can be separated
- m= metastable state

Source of Mo-99
- From fission of U-235 in nuclear reactor
- Bombard U-235 with thermal neutrons
- Nucleus splits into 2 daughter nuceli
- Not all nuclei split in same way
- Large range of nuclides produced
- Mo-99 can be separated relatively easily
- Main site- S.Africa, Holland
- None in UK
Technetium Generator
- Contains shielded glass column packed with alumnia
- Chemical form of Mo is molybdate- MoO42-
- Mo-99, as molybdate is strongly absorbed on to column
- Decays to produce pertechnetate- TcO4-
- Passage of saline through alumnia elutes pertechnetate
- Sodium (99-Tc) pertechnetate is used for one day
- MoO4- remains on alumina column and decats to produce more TcO4-
What happens on a molybdenum column

- Put in Mo99- this adherse to the aluminium column
- Mo99- breaks down into Tc99
- Saline is passed through the tube and flushes technecium out of the column
- Leaving molybdenum behind

Generator Elution

Transient equilibrium on column
- Molybdenum= 67 hr half-life
- Time to re-establish equilibrium is 22.89

Technetium level as fraction of maxium

Choice of generator
- Based on: Ease of operation; Efficiency and safety profile; Cost
- Practical points
- Must swab collection vial’s rubber bund
- Should elute in a grade A environment
- Make sure collection vial has reached atmospheric pressure before removal- try to prevent aerosol production
- Require shielding to protect operator
Radionuclidic purity/Identity
- This is defined by the B.P. as
- The radio, expressed as a percentage, of the radioactivity of the Radionuclide concerned to the total radioactivity of the source
- E.g. with 99Tc Sodium pertechnetate, what percentage is 99-mTcand how much is 99-Tc and 99Mo impurities are there
Radionuclidic purity/Identity
- 99-Tc/ 99-Mo generator
- Not done routinely
- Can identify unknown isotopes (e.g. if have a spill)
- Can be useful with unlicensed material
- Methods
- Molybdenum breakthrough test- if there is significant exposure after placing in sheild= molybdenum
- Gamma spectroscopy
- Measurement of energies emitted
- Measurement of decayed sample
- Determination of half-life
Sodium (99-Tc) pertechnetate
- Can be administered directly in that form
- Most common indication is thyroid imaging
- Why is pertechnetate taken up by thyroid
- TcO4 has similar shape and size to iodine
- TcO4 -tetrahedral- 4 x 10-23 cm3
- Iodide - spherical- 4.2x10-23 cm3
- Thyroid uptake
- ~2% of TcO4
- ~20% of iodide
Sodium (99-Tc) pertechnetate
- More commonly manipulated to produce Tc in different chemical form
- Different chemistry= different biodistribution
- Get information from different parts of body
- TcO4- chemically stable, Tc has valency of +7
- In order to make TcO4 react, need to alter valency state of Tc
- Oxidation states of -1 to +7 are known
Radiopharmaceutical Kit preparation
- 99mTc can exist in valency states of +7 to -1 and form range of co-ordination complexes
- It is eluted in most stable oxidation state (+7)
- All 7 electrons are shared with 4 oxygens
- Tc ion is surrounded by big O and ligand can’t get near
- Tin Ions in kit are more attractive to oxygens, which leave Tc leaving it highly reactive
- In this state can attach to ligand or may react with water to give Tc colloid

Radiopharmaceutical production

Modification of TcO4
- Might still have some of TcO4 and Tc-colloid there are impurities- they are not useful for scan they just irradiate the body so must be kept to a minimum
- Most vials are N rich- Not Oxygen because more oxygen will attach to Tc

Preparation of Technetium radiopharmaceuticals
- Simple technique- usually single addition of TcO4- to a kit- a freeze dried vial containing all required components
- Stannous chloride most frequently used reducing agent
- Kits commercially available products with product licences
- Generally multidose containers
- All manipulation performed aseptically
Precautions
- NEVER inject air into any technetium radiopharmaceutical vial
- The oxygen in 0.1mL air can oxidise the stannou ion used in many commercial kits as a reducing agent
Radiopharmaceutical kits
- Contain all the required ingredients for preparation of Tc radiopharmaceuticals
- Ligand, Sn++, buffers- pH affects oxidation state, stabilisers
- Single, sterile freeze dried rubber capped vial
- Vials contain nitrogen atmosphere
- Prevent oxidation of Sn2+
- Addition of TcO4 dissolves freeze dried powder and chemical reaction occurs
- Some kits need boiling
Ligand choice
- Choice of ligand important- structure of Tc-ligand determines biodistribution
- Compounds containing N,S,O and P atoms capable of sharing or donating electrons
- Over 20 different Tc complexes in routine clinical use
- Prepared daily as required in radiopharmacy department
- Preparation kept as simpple as possible
- Less handling- lower radiation exposure of staff
- Less chance of microbial contamination
- Less handling- lower radiation exposure of staff
Example: Tc-99m bone radiopharmaceuticals
- Methylene diphosphonate (medronate, MDP)
- P-C-P bonds resistant to phosphatase enzyme
- Can be labelled with Tc-structure
- Binds to hydroxyapatite Ca10(PO4)6(OH)2-imaging during bone growth- osteoblast
- Greater the bone turnover, greater uptake
- Can detect changes before change in bone density
Quality control of radiopharmaceuticals
- Radiochemical purity determination RCP is the % of the radionuclide that is present in the stated chemical form
- Mostly assessed through chromatography
- % of Tc-ligand should be >95% to pass
- % of free TcO4- and reduced Tc <5%
Quality control of radiopharmaceuticals

Quality control of radiopharmaceuticals
- Most assays rely on separation methods
- Column chromatography- HPLC
- Good separation but all activity may not be recovered from column
- Expensive equipment; requires expertise to un
- Planar chromatography- Use of stationary phase e.g. ITLC SG or filter paper + mobile phase
- Separation not always as good, but all activity may be measured
Quality of control of radiopharmaceuticals
Mobile phasesused
- Butanone or acetone may be used to separate 99m TcO4 from mixture
- Saline used to separated 99mTcO4 and 99mTc-ligand from 99mTc-colloid
- Exceptions include 99mTc MAG3 which is more difficult to separate

How will this affect the patient
- Free TcO4- will be taken up in salivary glands, thyroid and stomach
- Reduced Tc goes to liver and spleen- i.e. irradiation of unintended organs
- Sub-diagnostic images
- Repeat scan required- doubling radiation dose to the patient