1. 1
Synthesis and Labeling of DISIDA (N-2,6-
diisopropyl-phenyl
carbamoylmethyliminodiacetic acid)
Musa Lonwabo Kwetana and Otto Knoesen
NTP Radioisotopes (Pty) Ltd

2. 2
INTRODUCTION
•Radiopharmaceuticals are compounds labelled with a
radioactive isotope that are used for studying different
organs in the human body. Technetium-99m (99mTc)
labelled iminodiacetic acid (IDA) derivatives are
commonly used as hepatobiliary imaging agents;
•Radiopharmaceuticals used for hepatobiliary imaging
are divided into two groups based on thephysiologic
function of the liver they are designed to evaluate;

3. 3
Continued
•One group is used to evaluate the functional status of
the hepatocytes and patency of the biliary duct using
cholescintigraphy, and the other group the
phagocytic function of the Kupffer cell;
•Lipophilic compounds labelled with radionuclides
evaluate the first, and labelled colloids evaluate the
latter;
•The first iminodiacetic acid (IDA) derivative employed
in nuclear medicine was 2,6-
dimethylphenylcarbamoylmethyl iminodiacetic acid
(HIDA). Of all IDA compounds, DISIDA and
membrofenin are claimed to be the hepatobiliary
agents of choice. The IDA agent of choice for NTP is
DISIDA;

4. 4
Continued
•A cold kit is a pre-prepared vial containing DISIDA and
stannous chloride dihydrate as the reducing agent. DISIDA
kits are commercially available from NTP;
•The radioactive isotope of choice for IDA labelling is 99mTc;
•Labelling is accomplished by adding 99mTcO4- to the kit
and mixing well.
Review of DISIDA Scan:
• A DISIDA scan is a test that looks at the flow of bile through your liver and gallbladder.
• This scan is done to check the function of your liver and gallbladder. This helps determined the location of possible
gallstones, or if you have a blockage in the bile ducts that drain your liver.
• The material that allows us to see your liver and gallbladder contains a very small amount of radioactivity. This test
will result in very low radiation.

5. 5
EXPERIMENTAL
Synthesis of DISIDA
Step 1: Synthesis of the 2,6-Diisopropyl-
chloroacetanilide
2,6-Diisopropyl-chloroacetanilide is prepared by
reacting 2,6-Diisopropylanaline with
chloroacetylchloride in acetone according to scheme
1. The compound is isolated by addition of water;

6. 6
Continued
• Step 2: Synthesis of DISIDA
• 2,6-Diisopropyl-chloroacetanilide and disodium
iminodiacetate is reacted in ethanol: water (3:1)
according scheme 2. DISIDA is isolated by the
adjustment of the pH to 2.
• Characterisation
• DISIDA is analysed by
• • NMR
• • Melting Point
• • CHN analysis

7. 7
Continued
•Labelling and Quality Control of DISIDA
•Labelling is accomplished by adding 99mTcO4- to the
kit and mixing well;
•Quality control is performed with Silicic acid
impregnated instant thin layer chromatography paper
(ITLC-SA and ITLC-SG) with 20% NaCl solution and 85
% methanol as mobile phase. The activity distribution
is measured and recorded by a radiochromatogram
scanner; The Rf values are given in Table 1

8. 8
Continued
Table 1. Rf values of 99mTc labelled DISIDA kits
Stationary
phase
Mobile
phase
Rf
(99mTcO
4-)
Rf
(99mTc-
DISIDA
)
Rf
(Hydrolyzed
99mTc)
ITLC-SA 20 %
NaCl
1.0 0.0 0.0
ITLC-SG 85 %
Methanol
0.0 1.0 0.0

9. Continued
Biodistrubution of 99mTc-DISIDA
•The biodistribution DISIDA was confirmed by performing a
biodistribution study on a Chacma baboon. Results are
given in Figure 1.
9

10. Scheme 1. Synthesis of 2, 6-Diisopropylanaline with
chlo
roacetylchloride
10

11. Scheme 2. Synthesis of DISIDA (N-2, 6-diisopropyl-
phenylcarbamoylmethyliminodicetic acid).
11

12. GOALS FOR THE PROJECT
•Study the synthesis of DISIDA;
•Improve the overall synthesis yield;
•Study the labelling and quality control of DISIDA with
99mTc.
12

13. RESULTS
•The yield of the DISIDA synthesized was 66 - 76 gram (46
- 53%);
•The radiochemical purity of the labelled kits was > 95%;
•The experimental baboon study results are given in Figure
1 and conform to the standard biodistribution profile of
DISIDA.
13

14. CONCLUSION
•The yield of the DISIDA synthesis was improved from 26 –
34 g (18 – 24 %) to 66 - 76 g (46 - 53%);
•The labelling with 99mTc gave > 95% radiochemical
purity;
•The improved synthesis resulted in increased cost
effectiveness of the commercial DISIDA kits.
14

15. Figure 1. Structural formula of the IDA-type and its
coordinate to Tc (III).
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16. Figure 2. Biodistribution of DISIDA in a Baboon model.
Images are at 1 minute intervals.
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17. Acknowledgement
•NRF/DST Internship 2009/2010 and registration for SAIP
conference.
•Dr Otto Knoesen {NECSA(NTP)}
•WSU
•UP physics department even to give chance to study
further whereas they did not want to pay for SAIP
conference.
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18. REFERENCES
•Meitner L, Frisch OR (1939) Disintegration of uranium by
neutrons: a new type of nuclear reaction Nature 143:239-
240 [2]
•J.H. Burns, "Solvent-extraction complexes of the uranyl
ion. 2. Crystal and molecular structures of catena-bis(.mu.-
di-n-butyl phosphato-O,O')dioxouranium(VI) and bis(.mu.-
di-n-butyl phosphato-O,O')bis[(nitrato)(tri-n-butylphosphine
oxide)dioxouranium(VI)]", Inorganic Chemistry, 1983, 22,
1174-1178
•Decontamination of surfaces, George H. Goodalland
Barry.E. Gillespie, United States Patent 4839100
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19. Continued
•For other work on the iodine chemistry which would occur
during a bad accident, see [1][2][3]
•Glänneskog H (2004) Interactions of I2 and CH3I with
reactive metals under BWR severe-accident conditions
Nuclear Engineering and Design 227:323-9
•Glänneskog H (2005) Iodine chemistry under severe
accident conditions in a nuclear power reactor, PhD thesis,
Chalmers University of Technology, Sweden
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