Title of this slide no 1

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Production of radioisotopes where it all
begins!
Thomas J. Ruth UBC/TRIUMF PET Program Vancouver,
Canada
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PET beyond FDG In vivo Biochemistry
Placebo
In vivo Scatchard

11C-Methylphenidate
Compensation with disease progression
18F-Fluorodopa
11C-Dihydrotetrabenazine
11C-Dihydrotetrabenazine
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Why high specific radioactivity?

• Reduction of mass benefits synthesis and chemical
  separation
• Allows use of radiopharmaceuticals considered
  toxic
• Studies of biological events on tracer level
• In vivo studies of receptor systems with low
  density

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Specific radioactivity, SA
Nuclide SAmax Ci/mmol 11C
9200 13N 18800 15O 92000 18F 1700 3H
0.029 14C 0.000062 32P 9.1
- Amount radioactivity/mass Ci/mmol - SA
theoretical maximum SAmax NA ln2 /
T1/2 NA Avogardos number
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Eth 9.31
14O
Eth 0
15O
Eth 0
16O
2n
n
16O
g
14N
Eth 0
15N
p
T
dn
13N
a
d
Eth 4.91
14N
12C
Eth 12.06
Eth 0
Eth 0
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Accelerator Production

• Target Z ? Product Z
• High Specific Activity
• Low Energy - Fewer By-Products

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Positron Emitters
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Production Methods
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Parameters

• target construction
• target constituents
• irradiation conditions
• energy
• current
• temperature
• pressure
• dose
• optimize yield and specific activity

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11CCO2

• small volume aluminum targets
• O2 may or may not be added
• H. J. Ache, A.P. Wolf, Radiochim. Acta Vol 6,
  p32, 1966
• primary products are CN and CO at low dose (lt0.1
  eV/molecule)
• higher doses radiolytically oxidize these to CO2
• typical dose 150 eV/molecule

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11CCH4

• initial work to produce HCN in target required
  flow-thru quartz body due to dose dependence and
  CN reactivity.
• large aluminum or small nickel targets reported
  to work well.
• D.R. Christman et al. Int. J. App. Rad. Isot.,
  Vol. 26, p435, 1975.
• G.-J. Meyer et al. Radiochimica Acta, Vol. 50,
  p43, 1990.

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11CCH4

• Reaction Pathway

protons
N2 H2
11C N2 H2
11CN
11CN H2
HCN
HCN
CH4 NH3
radiolysis
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11CCH4 at TRIUMF

• initial results with cylindrical target, 5 H2
  very poor (30 theoretical)
• conical target, 10 H2 (50 theoretical)
• NH3 in equilibrium only dependent on amount of
  H2
• residual fields show 11C produced but not
  extracted in gas phase

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Y Ae-at I SF
Target chamber A a10000 Nb cylinder 95 ?
2 40 ? 4 Aluminum cone 78 ? 9 135 ? 44
Nickel cone 65 ? 9 527 ? 67 SS Cylinder 71
? 11 64 ? 62 Large Al Cylinder 70 ? 9 180 ? 52
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Production of 18F
Essentially 2 reaction routes to the production
of 18F 20Ne(d,a) _at_ 14MeV 18O(p,n) _at_ 17 MeV
Data from IAEA
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Nucleophilic 18F (F-) 18FF -, chemically
unreactive in many situations alkylation reagents
for O-, S- and N-fluoroalkylation high
production yield with low proton energy high
specific radioactivity - synthesis (development)
often laborious
Electrophilic 18F (F) 18FF2, 18FCH3COOF,
chemically reactive fast labelling synthesis -
low specific radioactivity - awkward targetry
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18FHF

• first water target was Kilbourn et al. Int. J.
  Appl. Rad. Isot. Vol. 35, p599, 1984.
• target materials, titanium, silver, nickel, gold
  plated, niobium, tantalum
• A.D. Roberts et al. NIM B99, p797, 1995.
• C. E. Gonzalez Lepara B. Dembowski, Appl. Rad.
  Isot. Vol. 48, p613, 1997.
• S.K. Zeisler, et al. Appl. Radiat. Isot.
  53449453 2000.
• N. Satymurthy, et al. Molecular Imaging and
  Biology. 4, 6570. 2002

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18F Water Targets as reported at WTTC10August
2004
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18FF2

• An 18O2 Target for the Production of 18FF2
• R. J. Nickles, M.E. Daube, and T.J. Ruth,
• Int. J. Appl. Radiat. Isot. Vol. 35, p117, 1984
• experience with 20Ne(d,a)18F carrier 19F2
• subsequent irradiations gt theoretical
• target wall acting as a holding pool for F
• NiF2 on target walls is not passive
• proton-only accelerators 3x yield

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Nickles 4 Compartment Model
k6
k7
k2
k1
k3
k5
k4
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Two-shot Method

• target evacuated
• O2 released to target and irradiated
• O2 cryotrapped out
• target evacuated with mech. pump
• target loaded with 20-200mmole F2 inert gas
  (Ne, Ar, Kr, Xe)
• 18F2 released from target via isotopic exchange

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Synthesis of 18FF2
mF2 n18FCH3F (m-3n)18FF2 n18FCF4
3n18FHF m gtgt n
Monte Carlo calculations for formation of 18FF2
Bergman J. and Solin O., Nucl. Med. Biol. 24
(1997) 677
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Synthesis of 18FCFT
Electrophilic labeling

18FF-
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Specific radioactivity for Fluorine-18
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Ultra High Yields for 18F Production
Production via 18O(p,n)18F reaction using gas
target _at_ 100 mA followed by recovery of target
gas. Wash target with water trapping 18F- on ion
column. Elute fluoride ion for chemistry with
standard solutions. Dry target for next run.
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Estimated Yields in Ci _at_ 100 mA
Ep TTY 2 Hour 4
Hour (MeV) _at_Sat. Irrad.
Irrad. 12 21 10.5
15.8 15 25 12.5
18.8 20 30 15
22.5
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Why 64Cu?
Half-life 12.7 hr Decay scheme combines
emissions positron ? (19) electron capture
(41 ), beta ?- (40) 578 MeV, Auger
electron emissions. Proton bombardment on
natural nickel, enriched 64Ni and 68Zn
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124I - Potential Radiotoxic Nuclide

• t1/2 4.14 d
• b emitter
• Production
• 124Te(p,n)124I _at_ 13 MeV
• 125Te(p,2n)124I _at_ 25 MeV
• 128Xe(p,an) 124I _at_ 23 MeV ???
• Natural abundance
• 124Te 4.74
• 125Te 7.07
• 128Xe 1.92

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For Gas Target

• After over 20 years post WTTC-1 what do we know?
• A number of things such as how to produce very
  high specific activity 11C-tracers, and gas
  density reduction due to beam heating.
• But we do not know enough, e.g. how to operate at
  high beam current with near theoretical yields!
• Heat transfer is probably the most dominate
  factor with which to contend.
• Recent evidence also points strongly to wall
  effects.

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Conclusions It appears that the in situ
production of 11CH4 is dependent upon not only
target geometry but also target chamber
material. For small volume targets there is a
tradeoff between the convenience of Al and the
production capabilities of other materials such
as Nb (??).
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However, it appears thatSize Counts when it
comes to controlling heat transfer and minimizing
wall interactions!Soooo
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Proposed Target
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Acknowledgements
The author wishes to thank Olof Solin of Turku
for use of his F2 slides, Ken Buckley and Salma
Jivan for all their help over the years. TRIUMF
is supported by a contribution form the National
Research Council of Canada.