Maximum Diagnostic Information with Minimum Risk.

Copyright

All images in this presentation are the property of Jane Hanrahan unless otherwise referenced.

Radiopharmaceutics

Dr Jane [email protected]

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.


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


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


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


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


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


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


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


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


8. Specific Receptor Binding

• Mainly in CNS

• [11C]-Raclopride (dopamine receptor antagonist

• [11C]-Flumazenil at GABA-benzodiazepine site

Maximum Diagnostic Information with Minimum Risk.

Documents

Transcript of Maximum Diagnostic Information with Minimum Risk.