presented by Mario Malinconico, Comecer R&D Specialist, at SNMMI Mid-Winter Meeting 2018 in Orlando, FL,USA. Discover new ALCEO features in this presentation

1. Synthesis of radiometals from solid
targets used for radiolabeling
Mario Malinconico, Comecer R&D Specialist

2. 2
ALCEO SOLID TARGET

3. GE PETTrace - Not shielded cyclotron
GE PETTrace - Self shielded cyclotron Generic external beam line
IBA Cyclone or Kiube cyclotron
Target System - PTS
• Installed in the cyclotron beam
exit port
• Receives the target shuttle from
the modules with a complete
automatic pneumatic transfer
(pipe 35 mm)

4. PTS & Cooling system
Cooling System
4
• Installed outside the bunker
• Cools down the target under
irradiation (He/water flows)
• Supply description
• Power
• Compressed air
• Helium cooling
• Water cooling IN and OUT

5. Shuttles
5
Shuttle dimensions : D28x35mm
Alceo Halogen 123/124I target
shuttle (Haynes alloy + Pt)
Alceo 64Cu Metal target shuttle
(Aluminium + Pt)
Alceo 68Ga Metal target shuttle
(Aluminium + Pt)
Alceo 89Zr Metal target
shuttle (Aluminium + Pt)
Hi-tmp melting shuttle Foil shuttle Plating shuttle
Alceo 45Ti Metal target
shuttle (Aluminium + Pt)

6. EDS 3.0
Main features
6
• storage targets
• Sending/receiving the target to/from PTS
• 64Ni plating
• 64Cu Dissolution
• 68Zn plating
• 68Ga Dissolution
• 89Zr Dissolution
• 45Ti Dissolution
PTS
TADDEO-PRF
Dissolutionirradiatedtaregt

7. EDS 3.0
Cross-contamination free and modular design
7
Ni Plating
Cu dissolution
Zr dissolution Zn Plating
Ga
dissolution
Dedicated circuit for NiDedicated circuit for Zn
Pick&Place
Pick&Place

8. Taddeo-PRF
• Dissolution
• Cu: hot HCl 6M
• Zr: HCl 6M drop-by-drop
• Ga: hot HCl 10M
• Purification
• Cu: ion exchange resin with 6M HCl.
• Ga: ion exchange resin with 1M HCl.
• Zr: hydroxamate resin with 1M oxalic
acid
8
• EDS or
• DISSOLUTION UNIT
Labeling
64Cu Production kit 45Ti/89Zr Production kit 68Ga Production kit

9. Improved Modularity
9
“Modularity” means:
• a single target able to produce all the isotopes with an automatic transfer system
• a single module able to produce different isotopes keeping safe the risks of cross-
contamination
• the possibility to switch between isotopes without complex setup and a quick
chemical preparation
64Cu 89Zr 203Pb
ALCEO METAL ALCEO HALOGEN
123/124I68Ga 45Ti 44Sc

10. 64Cu Production
10
Ni powder NiNO3 solution
• Electroplate
• Clean after plating
• Send
• Irradiate
• Receive
• Cu-Dissolve&Cu-Purify
• Ni recovery
• Clean after purification
• Waste cassette
64Ni
64Cu
64Ni(p,n)64Cu
15h
 9ml Copper Chloride in HCl 0,5M (new cartridge in the near future final volume 1,5mL)
 Expectd yield 1,5mCi/uAh (max current 40uA)

11. Hot Test – 64Cu
11
PAPER BURN
10uA 15sec
PLATING
44mg
BEAM
EOB 12:24
Current 30uA
Irradiation 2,18h
64Cu Production
Activity 146mCi
Measure Time 15:22
Yield (EOB) 2.5mCiuA
h
PAPER BURN
unknow
PLATING
48,5mg
BEAM
EOB 12:40
Current 30uA
Irradiation 1 h
64Cu Production
Activity 61,4
Measure Time 14:40
Yield (EOB)
2,28mCi/uA
*h

12. Hot Test – 64Cu
12
PAPER BURN
10uA 15sec
PLATING
49mg
BEAM
EOB 16:00
Current 35uA
Irradiation 6h
64Cu Production
Activity 518 mCi
Measure Time 18:00
Yield (EOB)
2.48mCi/u
Ah

13. ICPMS
13
DATE mg plating
Fe
(ppb)
Co
(ppb)
Ni
(ppb)
10/JAN/2017 46,2 8510 4.3 17180
11/JAN/2017 48,6 7300 3.8 22420
12/JAN/2017 47,1 3560 6 10950

14. Labeling
14
Method: [64Cu]CuCl2 was
added to H2-ATSM in
DMSO and allowed to
react over 5 min, then
purified over C18 to give
[64Cu]Cu-ATSM

15. 68Ga Production
15
Zn powder ZnCl2 solution
• Electroplate
• Clean after plating
• Send
• Irradiate
• Receive
• Ga-Dissolve&Ga-Purify
• Zn recovery
• Clean after purification
• Waste cassette
68Zn
68Ga
68Zn(p,n)68Ga
 5mL Gallium Chloride in HCl 1M
 Expectd saturation yield 45mCi/uA (max current 35uA)
6h

16. Hot Test – 68GA
16
PAPER BURN
PLATING
57,9mg
BEAM
Start Beam 10:00
EOB 10:19
Current 10uA
Irradiation 180min
68Ga Production
Activity
EOB
399mCi
Yield (EOB) 47,4 mCiuA
PAPER BURN
PLATING
49,1mg
BEAM
Start Beam 10:00
EOB 10:19
Current 10uA
Irradiation 20min
68Ga Production
Activity
EOB
45,31 mCi
10:19 (9/9/16)
Yield (EOB) 24,5mCiuA
DEGRADER 320um (14,4MeV)
DEGRADER 640um (12,1MeV)

17. Performances
17
GALLIUM (68Ga) CHLORIDE
SOLUTION FOR RADIOLABELLING
Gamma analysis comparison ALCEO-
GENERATOR production
European Pharmacopoeia
• Half life: 62-74min
Test Result
Radionuclidic purity % 67Ga at EOP = 0,019%
pH <2
Fe (ppb) Prod1: 332 Prod2: 1350
Zn (ppb) Prod1: 371 Prod2: 5130
GALLIUM (68Ga) CHLORIDE SOLUTION
FOR RADIOLABELLING
European Pharmacopoeia
Gallium-68: min 99.9 %of the total radioactivity
• pH = max 2.
• Iron = maximum 10µg/GBq.
• Zinc = maximum 10µg/GBq.

18. 18
68Ga-DOTATATE 68Ga-PSMA
Products
SYNTHESIS HPLC
EOS
activity
(MBq)
Synthesis
yield
Decay corrected
yield
Radiochemical
purity
Free
68Ga3+
DOTATATE 888 76,0% 88,6% 91,3% 0,25%
PSMA 570 79,2% 89,6% 99,0%
Not
detected

19. 89Zr Production
• Send
• Irradiate
• Receive
• Zr-Dissolve
• Zr-Purify
• Clean after purification
• Waste cassette
89Y
89Zr
89Y(p,n)89Zr
Foil D15, 5mm
thickness 0,25mm
 1,3ml Zirconium Oxalate in Oxalic acid 1M
 Expected yield 0,35mCi/uAh (max current 25uA)

20. Hot Test – 89Zr
20
PAPER BURN
8uA 12sec
BEAM
EOB 11:00
Current 23uA
Irradiation 18min
89Zr Production
Activity 3,59
Measure Time 13:00
Yield (EOB) 0,49
mCi/uA*h
PAPER BURN
10uA 15sec
BEAM
EOB 12:00
Current 30uA
Irradiation 3 h
89ZrProduction
Activity 104,5mCi
Measure
Time
18:07
Yield
(EOB)
1,17
mCi/uAh

21. 21
PAPER BURN
10uA 15sec
BEAM
EOB 12:24
Current 25uA
Irradiation 30min
89Zr Production
Activity 5,91mCi
Measure Time 14:52
Yield (EOB) 0,48mCi/uA*h
PAPER BURN
10uA 15sec
BEAM
EOB 10:30
Current 25uA
Irradiation 30min
89Zr Production
Activity 6,35mCi
Measure Time 12:35
Yield (EOB) 0,51mCi/uA*h

22. Gamma

23. 23

24. 45Ti Production
• Send
• Irradiate
• Receive
• Ti-Dissolve
• Ti-Purify
• Clean after purification
• Waste cassette
45Sc
45Ti
45Sc(p,n)45Ti
Foil D15, 5mm, thickness 0,25mm
 1,2ml Titanium Oxalate in Oxalic acid 1M
 Expectd saturation yield 9mCi/uA (max current 25uA)

25. Hot Test – 45Ti
25
PAPER BURN
10uA 15sec
BEAM
EOB
Current 25uA
Irradiation 2 h
89ZrProduction
Activity 75,7mCi
Measure Time
Yield (EOB) 8,43mCi/uA

26. Hot Test – 45Ti
26

27. Hot Test – 45Ti
27
45Ti
45Ti
45Ti
45Ti
89Zr

28. Alceo Halogen
The EVP module performs the following operations
automatically:
• target shuttle transfer between hot cell and cyclotron
• deposit of the isotope (Tellurium oxide melting) to be
irradiated inside the target shuttle
• iodine evaporation from the irradiated target
• iodine recovery via basic solution
The EVP is designed to eliminate problems related to the
module decontamination and cross-contamination because
it has been developed thanks to the “disposable cassette”
technology.
28
PTS

29. 123/124I Production
29
• Send
• Irradiate
• Receive
• Iodine Evaporation
(heat to trap iodine on glass support coated with NaOH)
• Iodine recovery
(to release the iodine using a basic solution)
Te
Iodine
Te(p,n)
I
TeO2 powder + alumina
• Melt

30. Performances
30
EXPECTED YIELDS
Isotope Max Current [µA] Typical Irradiation Time [h]
Yield EOB
[mCi/µAh]
Result [mCi]
Cu-64 40 6 ≥1,5 360
Zr-89 20 3 ≥0,35 20
I-124 10 6 ≥0,1 6
I-123 10 6 ≥0,4 24
EXPECTED YIELDS
Isotope
Max Current
[µA]
Typical Irradiation
Time [h]
Saturation Yield
[mCi/µA]
Ga-68 30 3 ≥45
Ti-45 25 3 ≥10
GALLIUM (68Ga) CHLORIDE
Saturation Yield [mCi/µAh] ≥45
Irradiation time = 3h
Applied current = 30µA
Expected Activity > 1Ci
68Ga production of 1100 mCi