Development of Germanium-68/Gallium-68 radionuclide generator

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DEVELOPMENT OF

GERMANIUM-68/GALLIUM-68

RADIONUCLIDE GENERATOR

S. Egamediev, S. Khujaev

Institute of Nuclear Physics of AS RUz, Tashkent

The 5

The 5thth _{EURASIAN CONFERENCE}_{EURASIAN CONFERENCE}

NUCLEAR SCIENCE AND ITS APPLICATION

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68

68 Ge

Ge



68Ga Generator

• The 68Ge

The 68Ge



_

68Ga generator is widely

used in diagnostic nuclear medicine.

• 68Ga radiopharmaceuticals as PET

68Ga radiopharmaceuticals as PET

agents are used for cancer tumor

localisation.

• The 68Ge is used as sealed source for

The 68Ge is used as sealed source for

attenuation correction in PET (positron

emission tomography).

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Nuclear Properties of Ge-68/Ga-68

radionuclide generator system

Radionuclide

Radionuclide Half-lifeHalf-life Mode of decayMode of decay (%)

(%)

Principal

Principal -rays-rays E of

E of -rays, -rays, keV

keV Yield of Yield of %%-rays, -rays,

Ge-68

271 days

EC (100)

none

Ga-68

68.1 min

EC (10)



+ (90)

511

511 1077

1077

180

3

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Excitation functions for Ge-68 production from

proton irradiated gallium targets

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Summary of Methods used for

Production of Germanium-68

Target

Target Nuclear processNuclear process Energy Energy range range used, used, MeV MeV Thick Thick target target yield, yield,  Ci/Ci/AA.h.h Production Production Yield, Ci Yield, Ci Chemical Chemical separation separation method method RbBr RbBr Rb,Br (p,spall)Rb,Br (p,spall) 800800 2.02.0 1.0 Ci 1.0 Ci per a 2 week per a 2 week irradiation irradiation Distillation, Distillation, solvent solvent extraction extraction with carbon with carbon tetrachloride tetrachloride Gallium-Niobium

Niobium natGa(p,xn)natGa(p,xn) 4545 1414 _{per a 4 week}_{per a 4 week}0.4 - 0.4 - 0.5 Ci 0.5 Ci irradiation irradiation Solvent Solvent extraction extraction with carbon with carbon tetrachloride tetrachloride Gallium-Nickel

Nickel 69Ga(p,2n)69Ga(p,2n) 22 22  13 13 1010 0.06 Ci per 0.06 Ci per runrun extraction extraction Solvent Solvent with carbon with carbon tetrachloride tetrachloride

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Distribution coefficients of 68Ge from the mixed solutions of

HNO₃+HCl and H₂SO₄+HCl

Composition of

aqueous phase Organic solvent

benzene toluene xylene CCl₄

8 M HCl 12 16 13 17 8 M HCl + 1 M HNO₃ 34 37 35 35 8 M HCl + 2 M HNO₃ 69 110 86 39 8 M HCl + 4 M HNO₃ 80 108 85 39 3 M HCl + 4 M H₂SO₄ 0.1 0.2 0.2 0.1 6 M HCl + 4 M H₂SO₄ 256 310 267 297 8 M HCl + 4 M H₂SO₄ 325 473 372 328

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Effect of the cooling temperature of HCl and target

solution on the radiochemical yield of Ge-68

№

№ Temperature of Temperature of HCl

HCl Temperature of target solution, Temperature of target solution,

 CC Radiochemical Radiochemical yield, % yield, %

1

1 -5

-5

18

46.2

2

2 -10

-10

20

52.0

3

3 -21

-21

17

63.1

4

4 -21

-21

4

90.0

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Separation of Ge

-68

from Ga-Ni target

•

The radioactive layer of target is dissolved in 25 ml The radioactive layer of target is dissolved in 25 ml

concentrated nitric acid. Then the target solution is evaporated concentrated nitric acid. Then the target solution is evaporated to damp salts and the rest is dissolved in 10ml of 10 M H2SO4. to damp salts and the rest is dissolved in 10ml of 10 M H2SO4.

•

Afterwards a portion of target solution (2 ml each) cooled to 4 Afterwards a portion of target solution (2 ml each) cooled to 4



C is diluted by 4 ml of preliminary cooled concentrated HCl C is diluted by 4 ml of preliminary cooled concentrated HCl acid as small as - 21

acid as small as - 21_C. Then the solution obtained is passed C. Then the solution obtained is passed through column at flow rate of 0.5 ml/min.

through column at flow rate of 0.5 ml/min.

•

After loading of all target solution the flask is washed twice After loading of all target solution the flask is washed twice with 5 ml portions of cooled 10 M HCl which is also passed with 5 ml portions of cooled 10 M HCl which is also passed through column. Then the column is washed with 10 ml of 8 M through column. Then the column is washed with 10 ml of 8 M HCl.

HCl.

•

Carrier-free Ge-68 is eluted with 4 ml of 0.1 M HCl. The eluate is Carrier-free Ge-68 is eluted with 4 ml of 0.1 M HCl. The eluate is collected by portions (0.5 ml each) into test tubes.

collected by portions (0.5 ml each) into test tubes.

•

It was found that the 90% Ge-68 is eluted in volume equal to a It was found that the 90% Ge-68 is eluted in volume equal to a half of the column’s free volume.

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Influence of pH on Adsorption of Ge-68

on alumina

pH pH Distribution Distribution coefficient coefficient of Ge-68, of Ge-68, ml/g ml/g Adsorption Adsorption of Ge-68, of Ge-68, % % Desorption Desorption of Ga-68 of Ga-68 with 0.1 M HCl, with 0.1 M HCl, % %

1

52

9

1.2

62

2

65

9

3

3 .0

.0

48

4

66

9

3

3 .0

.0

44

6

75

9

4

4 .0

.0

44

8

112

9

6

6 .0

.0

55

10

460

99.0

65

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Influence of temperature annealing of

alumina on adsorption and desorption of

Ge-68 and Ga-68

Temperature Temperature annealing, annealing, °C °C Adsorption of Ge-68 Adsorption of Ge-68 from 0.1 M HClfrom 0.1 M HCl Desorption degree Desorption degree with 0.1 M HCl with 0.1 M HCl Distribution Distribution coefficient

coefficient Adsorption Adsorption degree,%degree,% Ga-68, %Ga-68, % Ge-68,%Ge-68,%

400

128

96.2

40

0.3

0.3 1000

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Radiochemical bases of Ga-68 generator

•

Adsorption degree of carrier-free Ge-68 on alumina in the pH Adsorption degree of carrier-free Ge-68 on alumina in the pH range

range 10-1210-12 is is 99-99.399-99.3%.%.

•

It was found, that preliminary treatment of alumina (400 It was found, that preliminary treatment of alumina (400 _C) by C) by 0.1 M NaOH with subsequent sorption of Ge-68 at pH10-12 and 0.1 M NaOH with subsequent sorption of Ge-68 at pH10-12 and washing sorbent, containing Ge-68 by 0.1 M HCl assure

washing sorbent, containing Ge-68 by 0.1 M HCl assure

effective separation of Ga-68 from Ge-68 and yield of Ga-68 effective separation of Ga-68 from Ge-68 and yield of Ga-68 reaches 65%.

reaches 65%.

•

It was found that preliminary annealing of Al2O3 at 1000 It was found that preliminary annealing of Al2O3 at 1000 C C provides the best conditions for separation of daughter

provides the best conditions for separation of daughter radionuclide 68Ga from parent radionuclide 68Ge.

radionuclide 68Ga from parent radionuclide 68Ge.

•

it was decided to combine these two ways of preliminary it was decided to combine these two ways of preliminary treatment of Al2O3 in the preparation technology of

treatment of Al2O3 in the preparation technology of radionuclide generator of 68Ga.

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Drawing of container KSU-2 for

radionuclide generator

1.

1. HandleHandle

2.

2. Upper lidUpper lid

3.

3. Eluent line or tubeEluent line or tube

4.

4. FunnelFunnel

5.

5. Generator glass columnGenerator glass column

6.

6. MountingMounting

7.

7. Bottom lidBottom lid

8.

8. Eluate line or tubeEluate line or tube

9.

9. Angle needleAngle needle

10.

10. Air needleAir needle

11.

11. Vial for eluateVial for eluate

12.

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Testing of 68Ge



68Ga generator

No. elutions

No. elutions Volume of eluate, Volume of eluate, ml

ml _{of Ga-68, %}_{of Ga-68, %}Yield Yield Breakthrough Breakthrough _{of Ge-68, %}_{of Ge-68, %}

2 2 55 6767 < 0.0002< 0.0002 3 3 55 9696 <0.0002<0.0002 10 10 33 8888 <0.0002<0.0002 20 20 33 7777 <0.0002<0.0002 30 30 33 6060 <0.0002<0.0002 50 50 33 4040 <0.0002<0.0002 100 100 33 3636 <0.0002<0.0002 200 200 33 3636 <0.0002<0.0002

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Conclusions

•

A method for the production and separation of carrier-free A method for the production and separation of carrier-free

Ge-68 from gallium-nickel target was developed. Ge-68 from gallium-nickel target was developed.

•

The influence of preliminary annealing of Al2O3 on the The influence of preliminary annealing of Al2O3 on the

separation efficiency of Ge-68/Ga-68 radionuclide chain was separation efficiency of Ge-68/Ga-68 radionuclide chain was

studied. It is concluded that the Al2O3 sample which was studied. It is concluded that the Al2O3 sample which was

sequence annealed at 400

sequence annealed at 400 C and 1000 C and 1000 C is a suitable material C is a suitable material as a support medium for Ge-68/Ga-68 generator.

as a support medium for Ge-68/Ga-68 generator.

•

Elution yield of Ga-68 was 60-90% and results were Elution yield of Ga-68 was 60-90% and results were

reproducible during first month of the test. The breakthrough of reproducible during first month of the test. The breakthrough of

parent 68Ge was less than 2

parent 68Ge was less than 2_10-4%. Dissolved aluminum from 10-4%. Dissolved aluminum from the column containing 2.5 g of Al2O3 with a 0.1 M HCl was

the column containing 2.5 g of Al2O3 with a 0.1 M HCl was found to be 1

found to be 1 _g/ml.g/ml.

•

These studies are carried out in framework of the STCU project These studies are carried out in framework of the STCU project of Uz-25

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