International Workshop PSD-11...

International Workshop PSD-11 Delft

Clive Naidoo (PhD Chemistry)

Dept Head: Radionuclide Production

iThemba LABS

South Africa

Electronic and Information Services

Accelerator Infrastructure

Directorate

HR, Finance & General Admin

Technical Support & Site Services R

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iThemba LABS Structure

RPD OBJECTIVES

• To produce radiopharmaceuticals for the benefit of the

South African Nuclear Medicine community.

• To produce longer-lived radionuclides for the export

market.

• Research & Development and Training Program.

iThemba LABS Layout

Separated-Sector Cyclotron FacilitySeparated-Sector Cyclotron Facility

0 10 20 m

beambeamswingerswinger

SSCSSC

SPC1SPC1SPC2 SPC2

Polarized ion sourcePolarized ion source

ECR ion sourceECR ion source

RadioisotopeRadioisotope production production

Neutron therapyNeutron therapy

SpectrometerSpectrometerTarget vaultsTarget vaults

electronicselectronics electronicselectronics

Proton therapyProton therapy

Separated Sector Cyclotron (200 MeV)

RPD beam time allocation

Monday night 17h00 to 7h00 (14 h)

Tuesday night 17h00 to 7h00 (14 h)

Wednesday night 17h00 to 7h00 (14 h)

Thursday night 17h00 to 5h00 (12 h)

On average 54 h / week (32%)

RPD beam time allocation

with beam splitter

Radionuclide Half-Life (hours)

Nuclear Reaction Radiopharmaceutical

Product

Main Use

18F 1.83

15O(p,n)

18F

18F-FDG Glucose metabolic

studies 67

Ga 78.3 Zn(p,xn)67

Ga

Ge(p,x)67

Ga

67Ga-citrate Localization of

certain tumours and inflammatory

regions 81

Rb/81m

Kr 4.58 Kr(p,xn)81

Rb 81

Rb/81m

Kr generator Lung ventilation studies

123I 13.2 127

I(p,5n)123

Xe 123

I

123I-sodium iodide

123I-mIBG

Thyroid studies

Localization of certain tumours

such as neuroblastoma,

pheochromocytoma 68

Ge/68

Ga

generator

68Ge = 271 d

68Ga = 68 min

69Ga(p,2n)

68Ge

68Ga –DOTA-peptides Typically detection

of neuroendocrine tumours

iThemba LABS Products produced

under cGMP principles

Radionuclide Half-Life (days/years)

Nuclear Reaction Main Use

82Sr 25 days Rb(p,xn)

82Sr Used to manufacture

82Sr/

82Rb

generators 68

Ge 271 days Ga(p,xn)68

Ge Used to manufacture 68

Ge/68

Ga generators and calibration sources for

PET CT scanners 88

Y 106.6 days Sr(p,xn)88

Y Non –medical application –calibration sources

109Cd 453 days Ag(p,xn)

109Cd Non-medical application-calibration

sources 22

Na & 22

Na positron sources

2.602 years Mg(p,n)22

Na Used in Material Sciences -Positron Annihilation Studies

iThemba LABS other products

Horizontal Beam Target Station (HBTS)

Produce: 67Ga, 123I, 81Rb, 68Ge, 82Sr, 22Na, 88Y, 57Co and 109Cd

HBTS Target and target holders

66 MeV proton beam with an intensity of ~90 µA

Vertical Beam Target Station (VBTS)

VBTS Tandem targets 66 MeV proton beam with an intensity of ~250 µA

VBTS Thick Target Holders

VBTS Tandem targets

Produce in Tandem 82Sr/68Ge and 22Na/68Ge

18F- Bombardment Station

18F Target Station (66 MeV to 18 MeV)

Enriched water target

Target Control System

Beam Splitter

RPD Control Room

Automated Transport System Control systems such as cooling systems (water and helium), interlocking systems

and transport system

18F-Automated Chemical

Processing Hot Cells

Chemical Processing Facilities

Manual Manipulator Hot Cells (two banks of 7)

3 Independent clean rooms

68Ge/68Ga 18F-FDG

123I /67Ga

Dispensing facilitiesnts

Comecer Hotcells & Timothea Dispensing Facilities

Quality Control Facilities

GC

Capintec Ionisation Chamber

HPLC

Quality Control Microlab

Sterility and endotoxin testing

QC Raw material

Packing and Dispatch

As per IATA Regulations

Tandem target for the production of 22Na and 68Ge

65.762 MeV 36.635 MeV 62.579 MeV 61.476 MeV

20 mm

40.013 MeV 38.444 MeV 36.866 MeV 34.364 MeV 2.364 MeV

66 MeV

protons

Mg material: 99.99% (15 g)

Chemical Processing

A magnesium target (ca 15 g, 12 mm thick, 20 mm diameter) is bombarded for several weeks

with a 66 MeV proton beam at a beam current of 80 μA (in the higher energy window 61.5 →

40.0 MeV). [Generally production rate is 1 mCi / h).

The target is dissolved in 3.0 M citric acid and then adjusted to obtain a 0.2 M citric acid - 0.6

M TEA - 80% methanol solution.

The solution is pumped through a column containing 10 g of the macroporous cation

exchanger AG MP – 50.

Washing solutions: 0.2 M citric acid - 0.6 M TEA - 80% methanol, followed by 0.1 M EDTA -

0.6 M TEA. The resin is then converted to the ammonium form with 1.0 M ammonia – 80%

methanol and 22Na is eluted with 1.0 M ammonium carbonate (100 ml) passing through 10 g of

the chelating resin Chelex 100 (in the ammonium form) to remove the last traces of

magnesium and other elements.

The eluate is heated in a conical titanium vessel to evaporate the ammonia and water. 22Na is

obtained as the carbonate salt in a small volume.

All reagents are purified to remove sodium prior to the ion exchange separation

Final Specification: >800 Ci 22Na / g

22Na Chemical Processing hot cell panel

The specified amount of 22Na carbonate solution is dispensed from the bulk vial and placed in a V-vial and

evaporated to about 20-30 µl. Final activity check is done with the Capintec Ionisation Chamber.

The rear part of the capsule is clamped in a holder with the post facing upwards and level.

The 22Na is then transferred, in 10 μl volumes, into the tantalum cup with a semi-automated dispensing

apparatus. This is evaporated to incipient dryness, before the next volume is dispensed.

When all the activity of 22Na has been transferred into the cup, the front part of the capsule is loosely

screwed onto the rear part.

The capsule is finally sealed to a defined torque value (20 Nm) using a special holder to clamp the capsule

tightly.

The external surface of the capsule is washed with methanol and then rinsed with deionised water.

The capsule is dried and a smear test is done.

The source is then placed under vacuum for 24 h to ensure integrity of the capsule.

The washing step is repeated and another smear test is done after the vacuum test.

The positron capsule is then packed into a lead pot, the lead pot is sealed and finally packed in a container

for shipment to the user.

Capsule Dispensing

Positron Capsule

Dispensing apparatus

Holder to seal the capsule

Apparatus for vacuum testing

HPGe detector for final measurements

Na-22 sales and forecasts

Limited beam time for the irradiation of Mg targets at iThemba LABS.

Alternative company’s that could produce 22Na does not meet iThemba

LABS product specification of >800 Ci 22Na / g for large sources.

Alternative company’s needed to irradiate the Mg target material and for

iThemba LABS to do the chemical processing, not economical viable

(cost of irradiation US$ 6000 / mCi 22Na).

The production of sources is limited to a maximum of 50 mCi for the ease of

handling and to minimise radiation exposure to staff .

NB:

Upon receiving the larger sources from iThemba LABS, just do your smear

tests as required by your RPO and install.

Production Challenges

Thank You For Your Attention

clive@tlabs.ac.za