maximum diagnostic information with minimum risk
TRANSCRIPT
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All images in this presentation are the property of Jane Hanrahan unless otherwise referenced.
Ideal Radiopharmaceuticals
1. Half-life should be short - isotope has high specific activity
ie rapid decay rate, high No. of dps per weight of material
2. No particulate radiation emission - want pure gie no -, +
3. g energy high enough to be detected emanating from deep tissue - but low enough to be detected efficiently
Ideal energies 120 to 240 keV
Maximum Diagnostic Information with Minimum Risk
Ideal Radiopharmaceuticals
4. Radionuclide should be an element with variable chemistry
Enables preparation of a wide range of compounds for different diagnostic purposes
5. Radioisotope should be carrier-freeWant to maximise activity/g - no cold
material, reduces toxicity problems
6. Large scale production is achievable and economical
Technetium-99m (99mTc)
T1/2 = 6.02 h
High specific activity
Decays by isomeric transition
99Mo 99mTc (excited state) 99Tc (ground state)
Pure -emission with energy 140 keV
Known valences 2, 3, 4, 5, 6, 7 Variable chemistry, most common Tc3+, Tc4+
Readily prepared carrier free
Technetium-99m (99mTc)
99Mo(67 h)
99mTc(6 h)
99Tc(2.1 x 105 y)
99Ru(stable)
86.3 %
13.7 %
metastable
Isomeric transitionPure emission
Radionuclide Generators
Ideal Radionuclide Generator
1. Sterile and pyrogen free
2. Saline eluent
3. Mild chemical conditions
4. Room temperature storage
5. Ideal gamma-emitting daughter nuclide
6. No parent present in eluent
7. Parent half-life short enough so that production of daughter is rapid enough, but not too rapid.
Radionuclide Generators
Ideal Radionuclide Generator
8. Daughter nuclide has varied chemistry to allow production of many different radiopharmaceuticals
9. Grand-daughter nuclide is very long-lived or stable
10. Shielding of generator is not too difficult
11. Separation is simple and does not require a great deal of human intervention
12. Generator is easily recharged by a readily available parent radionuclide
Radionuclide Generators
http://www.orau.org/ptp/collection/nuclearmedicine/tc99mgenerator.htm
http://nuclear.pharmacy.purdue.edu/what.php
http://www.frankswebspace.org.uk/ScienceAndMaths/physics/physicsGCE/D1-1.htm
99Mo/99mTc Generator most widely used generator system
mother nuclide 99Mo (t1/2=67 h) decays into the daughter nuclide 99mTc (t1/2=6 h)
Milking cow analogy
http://www.clipartheaven.com/show/clipart/agriculture/milking_cow_6-gif.htmlBasics of Radiopharmacy, B.A Rhodes & B.Y.Croft, Chapter 9, Generator Systems. (1978)
Other Generator Systems
Quality Control
Impurities eluted with the Na99mTcO4 in the saline.
Alumina Breakthrough
Radiochemical purity
pH
Sterility
Apyrogenicity
Quantification
Radioactivity
Activity
Number of disintergrations per second (Bq)
Rate of disappearance of radionuclide
- dNd
t
N
- dNd
t
= kN
1/2
t= ln2
k
where
t 1/2
= ln2k
N = number of radioactive nucleik= constant specific for each isotope
k=1
Quantification
At = A0e-kt
Exponential decay
time
Radioactivity
(Bq)
Example 1How many moles of 99Mo does 15 GBq represent, t1/2=67h
- dNdt
= kN 15 GBq = 15 x 10 9 Bq
1/2
t=ln2
k = 0.693/(67x60x60)
= 2.89 x 10-6 sec-1
N = 15 x 10 9
2.89 x 10-6
dps
sec-1
= 5.33 x 1015 atoms Avogadro’s No. = 6.023 x 1023
No. of moles = No. of atoms
Avogadro’s No.
= 5.33 x 1015
6.023 x 1023
= 8.85 x 10-9 moles
Example 2How many grams of 99Mo does 15 GBq represent, t1/2=67h
From previous slide
15 GBq = 8.85 x 10-9
moles
1 mole 99Mo = 99 gram
Therefore 8.85 x 10-9 moles = 8.85 x 10-9 moles x 99 grams
= 8.76 x 10-7 grams
= 0.876 µg
Example 386.3 % of 99Mo decays to 99mTc with a half life of 67 hours. A 99mTc generator is filled with 15 GBq of 99Mo at 9 am on Friday morning and the 99mTc is eluted from the generator with 90 % efficiency, how much activity of 99mTc per ml can we get from the generator at 9 am on the following Monday morning in a 10ml elution.
At = A0e-kt = 15e-(ln2/67)72
= 15 x 0.475 = 7.125 GBq
99mTc activity in generator = 0.863 x 7.125 = 6.149 GBq
Amount eluted = 0.9 x 6.149 = 5.53 GBq = 0.553 GBq/ml = 553
MBq/ml
Example 4At 2 pm on the same Monday as the original elution, what volume of the previously eluted solution would need to be dispensed for a skeletal scan requiring 250 MBq of 99mTc.
t1/2 99mTc = 6 h
At = A0e-kt = 553e-(ln2/6)5
= 533 x 0.578 = 307.9 MBq/ml
For 250 MBq, volume of solution = 250/308 = 0.81 ml
At 9am, solution has 533 MBq/ml
Therefore at 1 pm, activity of solution is
Mechanism of Localisation
1. Simple Diffusion
- net movement of particles (molecules) is from an area of high concentration to low concentration.
- normal versus abnormal distribution using Na99mTcO4
eg breakdown of blood brain barrier due to tumours or
infarct damage in brain
Mechanism of Localisation
2. Active transportUptake radionuclide from blood using normal biochemical processese.g. thyroid trapping of 123I or Na99mTcO4 or hepato-
billiary imagingRenal imaging - 99mTc complexed with DTPA (diethylene
triamine pentaacetic acid)
Outflow obstructionRenal artery narrowingVesico-uretic refluxRenal transplant
assessment
2 TcO4- + 3 Sn2+ + 16 H+ Tc4+ + 3 Sn4+ + 3 H2O
DTPA
Renal Imaging with 99mTc-DTPA
Mechanism of Localisation
3. Cell SequestrationLiver, spleen and bone marrow uptake of colloidal particles by reticulo-endothelial (Kupfer) cellseg technetium sulfide colloid 99mTc2S4 Renal imaging
Particle size ~ 0.1 µm trapped in liver or spleen
Re2S7 is used as a carrier
2HCl + 2 Na2S2O4 H2SO4 + 2 NaCl + H2S + SO2
2 H+ + 7 H2S + 2 TcO4- Tc2S7 + 8 H2O
Mechanism of Localisation
4. Capilliary Blockade
Large particles trapped by lung arterioles (~ 20 µm)
eg for pulmonary perfusion studies99mTc labeled macroaggregated albumin (MAA)or 99mTc labeled macroaggregated ferric hydroxide
Ventilation studies - radioactive gas 133Xeor aerosol radiopharmaceuticals99mTc as carbide - “Technegas”99mTc as sulfur colloid
Inhallation then washout - airway obstruction “hotspot”
TcO4- Tc4+ Tc(OH)4
reduction -OH + FeSO4
Capilliary Blockade
Mechanism of Localisation
5. Compartmental localisation
- placement of a radiopharmaceutical in a fluid space and maintaining it there long enough to image that fluid space. e.g. Retention of labeled 99mTc-labelled RBC or proteins in vascular pools
Methodsa) Remove blood sample & incubate with Na99mTcO4 for 15
min and then administerb) “Pre-tinning” - administer SnCl2 in saline, wait 30 min,
then administer labelled RBC ( ~ 700 MBq Na99mTcO4)
“Gated” heart studies - collect images in synchrony with ECG at rest and under stress
Labeling RBCs
Mechanism of Localisation
6. Chemisorptioninteraction of labelled phosphate complexes with bone
Skeletal imaging - metabolically active sites
- soft tissue tumours - metastatic lesions - rheumatoid arthritis
Methylene diphosphate
Na99mTcO4 + SnCl2 Tc4+ + phosphate compound
Mechanism of Localisation
7. Specific cell bindingpreferential uptake by tumour cells
eg labelled tumour associated marker compounds or monoclonal antibodies
Radiopharmaceuticals for Tumour
Imaging 131I (sodium iodide)
- thyroid
67Ga (gallium citrate) - lymphoma, hodgkin’s disease, lung tumours, bone
tumors- Decays by electron capture (EC) t1/2 78 h
- g energies, 93 keV (40 %), 184 keV (24 %), 296 keV (22 %)
- 67Ga binds to transferin in plasma- Biodistribution is non-specific- Uptake is influenced by a number of factors
Radiopharmaceuticals for Tumour
Imaging 111In (complexed with Bleomycin or
monoclonal antibodies) - t1/2 78 h
- energies, 173 keV and 247 keV
protein chelating groups
Mechanism of Localisation
8. Specific Receptor Binding
• Mainly in CNS
• [11C]-Raclopride (dopamine receptor antagonist
• [11C]-Flumazenil at GABA-benzodiazepine site