Radiochim.
Acta 88, 2012205 (2000)
 by Oldenbourg Wissenschaftsverlag, München
11
C-methane production in small volume, high pressure gas targets †
By K. R. Buckley 1, J. Huser 1, S. Jivan 1, K. S. Chun 2 and T. J. Ruth*,1
1
TRIUMF, Vancouver, B.C. V6T2B5, Canada
2
Korean Cancer Center, Seoul, Korea
(Received November 9, 1999 ; accepted in revised form January 25, 2000)
11
C-methane / Small volume gas target /
Low energy protons
Summary. The parameters affecting the production of 11C-
methane, in situ, in small volume, high-pressure gas targets
include target chamber size and material. The results are based
on experiments that varied the target gas composition, the tar-
get material and geometry. Methane production yields were
typically 65% of the yields of 11CO2 in the same target cham-
ber.
Introduction
Typically 11C is produced as either CO2 or CH 4, in situ, for
later conversion to a precursor that is amenable to labeling
radiotracers for PET [1]. Nearly all of the labeling pro-
cedures at our center make use of methyl iodide as the
labeling agent. The gas phase production of 11C-CH 3I from
11
CH4 has been reported [2, 3]. In both reports 11CO2 was
produced in a gas target using the (p,A) reaction on nitrogen
gas followed by in-line conversion to 11CH 4. We have built
our own system based on providing 11C-CH4 directly from
the target. This approach eliminates the need to convert
CO2 to CH4 and may also eliminate the contamination of
none radioactive carbon species as long as the hydrocarbon
content of the target gases is less than the corresponding
CO2 that may enter the system from multiple sources. Thus
this approach should provide very high specific activity
11
CH4 and 11CH3 I.
While the in situ production of 11C-CH 4 has been de-
scribed in the literature, [426] most of these investigations
make use of large volume target chambers and the ir-
radiations were performed at energies above 15 MeV. An-
ecdotal evidence from the Workshops on Targetry and Tar-
get Chemistry indicates that attempts to generate 11CH4 in
small volume targets have not been very successful [7].
Thus the following paper describes our efforts to produce
11
C-CH 4 in a small volume, high-pressure target with a
13 MeV cyclotron.
Methods
All irradiations were performed on the TR13 cyclotron, a
fixed energy, negative ion 13 MeV proton cyclotron. The
†
Dedicated to the memory of Professor Alfred P. Wolf.
* Author for correspondence (E-mail: truth@triumf.ca).
Table 1. Target chambers and their dimensions.
Target chamber Dimensions
Al cylinder 1 cm dia., 10 cm long ; 8 mL
Al cone 1 cm taper to 2 cm, 12 cm long ; 24 mL
Ni plated Al cone 1 cm taper to 2 cm, 12 cm long ; 24 mL
Stainless steel cylinder 2 cm dia., 10 cm long ; 31 mL
Large volume Al cylinder 3 cm dia., 12 cm long ; 85 mL
negative H2 ions are stripped of their electrons and the
proton beam is extracted through a short beam transport
system that includes a four-sector collimator to the target.
The beam at the entrance foil of the target is guassian in
shape with a FWHM of about 6-mm. The collimator open-
ing is a 10-mm circle. The target chamber included a
double foil helium-cooling chamber. Helium flow through
this chamber is 74 liters per minute at 9 psi. The foils were
composed of 25 µm thick aluminum for vacuum isolation
and 39 µm thick Havar  for target gas isolation. The en-
ergy of the proton beam on the target gas is estimated to
be about 12 MeV.
The target chambers tested were composed of a variety
of materials and dimensions as shown in Table 1. For each
of these targets, irradiations were performed using 0.5%
O2/N 2 for 11CO2 production and either 5% H2 /N2 or 10%
H2/N 2 for 11CH4 production. The nominal target loading
pressures were 300 psi (2067 kpascals).
It should be noted that for the large volume and stainless
steel targets cooling was provided via water flowing
through a copper tube wound around the chamber. This
configuration did not provide as efficient cooling as in the
other target configurations as evidenced by the fact that
after irradiating these targets the pressure within the target
did not immediately return to baseline as is the case for the
other targets, each of which had a cooling jacket enclosing
the target chamber. The residual increase in pressure is at-
tributed to an elevated temperature within the target gas.
Ammonia is co-produced from radiolysis of the nitro-
gen-hydrogen gas mixture [4]. To investigate the effect of
in-target ammonia formation on methane production we
measured the ammonia for a series of target irradiations on
both the cylindrical targets and the conical targets. After
irradiation the target gas was passed through a HCl solution
to trap the generated ammonia and then through an Ascarite
202
trap to remove moisture followed by a trap of Porapak N
cooled in liquid nitrogen to trap the methane. Finally the
exhaust gas was collected in a holding bag. In order to
determine the quantity of ammonia produced under differ-
ent conditions 2.0 to 5.0 mL (determined by weight) of
0.50 N HCl solution was pipetted into a 10 mL Reactivial.
The ammonia produced in the target consumes a portion of
the HCl via the formation of NH4 Cl. The remaining quan-
tity of HCl is subsequently determined by titration with
NaOH to an endpoint of phenol red. The target gas was
bubbled through the solution at approximately 150 mL/min.
The target was flushed three times and the gas collected
as above. The solution was transferred quantitatively to an
Erlenmeyer flask containing 20 mL water and back titrated
with 0.10 N NaOH. The change in quantity of HCl from
before and after emptying was calculated. Blank runs were
used to calibrate the system. Initial experiments used two
such HCl traps, in series. However, the first trap consumed
the ammonia quantitatively and the second trap was no
longer used. In order to determine whether the production
of ammonia was a function of dose rate and/or total dose,
a series of irradiations were performed starting with very
short irradiations (1 minute) at low and high beam cur-
rent as well as longer irradiations, also at various beam
currents.
Samples of the irradiated gas mixtures (N 2/10 % H2)
were analyzed by radio gas chromatography (GC) to deter-
mine the radiochemical species formed. Radio gas chroma-
tography of the target gas was performed on an HP 5840 
chromatograph with an Alltech CTR1 column. The
CTR1 is a dual concentric column allowing the simul-
taneous separation of CO, CO2 , CH4, O2 , and N2 . Radioac-
tivity detection was accomplished with a 2′′ NaI detector
facing a coil of 1/16′′ OD tubing following the column.
The carrier gas was helium flowing at 55 mL/min and all
measurements were performed at ambient temperature.
Yield measurements were performed by collecting the
11
CH4 in a Porapak N trap cooled to liquid nitrogen tem-
perature. The total amount of radioactivity was determined
using a calibrated ion chamber (Capintec ). For the 11CO2
measurements, the CO2 was simply frozen out in a stainless
steel trap with a stack of stainless steel frits at liquid nitro-
gen temperatures. Individual radioactivity measurements of
the trap(s) were repeated until the decay corrected values
Target Gas NH3 Volume of
(total H2 ) (mmoles) target/gas
(mL)
Aluminum cone 5% H2
(1.1 mmoles) 0.054 24/480
Aluminum cone 10 % H2
(2.1 mmoles) 0.13 24/480
Nickel plated cone 10 % H2
(2.1 mmoles) 0.25 24/480
Stainless steel 10 % H2
cylinder (2.8 mmoles) 0.39 31/620
Large volume 10 % H2
Al cylinder (7.6 mmoles) 0.98 85/1700
K. R. Buckley, J. Huser, T. J. Ruth et al.
were consistent with the half-life of carbon-11. The differ-
ent target chamber materials were used to measure yields
as a function of dose rate and total dose.
Specific activity of the generated 11CH4 was not mea-
sured directly due to the lack of reliable standards. We have
however measured the specific activity of a number of
radiopharmaceuticals by determining a response curve for
our HPLC system. For example, a standard solution of
raclopride tartrate was prepared and aliquots of varying
concentrations were prepared covering the range of moles.
A straight-line curve was generated based on the integrated
plots of the UV response of the HPLC system. Subsequent
measurements of a defined volume of radioactive raclo-
pride were compared to the response curve for estimating
the mass of raclopride present. The specific activity was
calculated based on the radioactivity per unit volume and
mass of raclopride per unit volume.
Results
The resultant data shown in Table 2 indicate that the pro-
duction of ammonia in the target is dependent on the total
quantity of H2 present. The ammonia is produced quickly
and remains at equilibrium concentrations while the CH4
saturated yield drops with increasing run duration (see
Table 3).
The quantity of ammonia appears to be produced within
the first minute of irradiation and does not change after that
point reflecting the establishment of a rapid equilibrium
between nitrogen, hydrogen and ammonia. The amount of
ammonia produced did not change with beam current. Thus
the dose rate and total dose on target had no measurable
effect. In addition, the quantity of hydrogen present in the
targets exceeded the requirements for ammonia production
by more than an order of magnitude. The difference be-
tween the two cone targets is not understood.
A log plot of the radio GC data shows a small amount
of 13N-N2 as expected from the 11.3 MeV threshold of the
14
N(p,pn)13N reaction. Any 13NH3 present would have been
below detection limits due to the fact that the fraction of
ammonia formed to total N2 present is 0.016 or less. For
the H2/N 2 mixture the only 11C species was methane.
The 11CH 4 yields for the Aluminum conical target are
listed in Table 3 for H2/N2 gas mixtures. Theoretical yields
Table 2. In situ production of NH3 at 20 µA
[NH 3] [NH 3]/[H2 ] for 20 minutes for various target configura-
mmoles/mL tions. Nominal loading pressure was 20 atmo-
target gas spheres.
0.00011 0.049
0.00027 0.062
0.00052 0.12
0.00063 0.14
0.00058 0.13
11
C-methane production in small volume, high pressure gas targets 203

Table 3. Saturation yields for the small bore cylindrical Aluminum and concerned that the ammonia production was consuming the
conical Aluminum targets. Theoretical thick target yields for 10 % H2 /
hydrogen preferentially. However the results in Table 2
N2 target is estimated to be 92 mCi/µA.
indicate that this is not the case. Increasing the H2 concen-
Target Beam Length of Sat. % tration to 10% provided conditions where for low current
gas current irradiation yield Theo- runs of short duration the yields for the conical Al target
(µA) (min) (mCi/µA) retical are nearly theoretical. However at higher beam current runs
Cylindrical 15 1 81 88
and/or longer irradiations the yields drop off dramatically.
5% H2/N2 5 32 35 In order to determine whether the target geometry was
10 26 28 affecting the yields, we measured the 11CO2 yields in the
Cone 15 5 33 36 same targets as a comparison. The 11CO2 production rates
5% H2/N2 10.8 26 (n 5 2) 28 for our targets, Table 4, agree well the published results
20 10.7 42 (n 5 4) 46 (96 mCi/µA at saturation) [8]. Table 4 also presents the
31 35 38 measured and predicted yields for the 10% H2 /N2 gas mix-
10 % H2/N2 5 2 93 100 ture. The theoretical thick target yield as reported in Bida
10 2 101 110 et al. at 12 MeV is 96 mCi/µA at saturation. For a 10% H2
10.3 77.2 (n 5 3) 84
60 74 80
mixture the thick target yield is calculated to be 92 mCi/
20 1 86.3 94 µA.
2 81.7 (n 5 4) 89 In our centre raclopride labeled with carbon-11 provides
2.4 86.4 (n 5 3) 94 the most reliable measure of specific activity and at the
5.8 67.7 (n 5) 74 same time reflects the best specific activities measured to
10.2210.9 57.4 (n 5 8) 62
20.9 60 65 date. Typical values range from 5 to 10 Ci/µmole at end of
30 51 56 synthesis (EOS) which is typically 45 minutes post end of
30 2 56 61 bombardment. Thus the 11CH 4 methane is assumed to be in
3 50 54 excess of 40 Ci/µmole. We have on occasion measured
10.2210.8 47.3 (n 5 3) 51
specific activities as high as 20 Ci/µmole EOS for the raclo-
pride.

have been calculated taking into account the N2 target con-

centration and the change in stopping power due to the Discussion
addition of hydrogen to the target gas. Our initial experience with the 1-cm cylindrical aluminum
From the results presented in Table 3 it can be seen that target led us to explore an alternate target chamber ge-
the 5% H2 target performed very poorly. At first we were ometry such as a conical target that would compensate for

Table 4. Thick target yields for the different

target geometries. Nominal target pressure was Target Gas Time Yield @ Sat. yield %
300 psi and the beam current was 20 µA. (min) EOB (mCi/µA) Theo-
(mCi) retical

Aluminum cone 10 % H2 5 210 67 73

20 608 60 65
30 658 51 56
Aluminum cone 0.5 % O2 5 276 88 92
20 811 82 85
30 1038 81 84
Ni plated cone 10 % H2 10 228 39 42
20 209 21 23
30 180 14 15
Ni plated cone 0.5 % O2 5 238 76 79
20 713 72 75
30 933 73 76
SS target 10 % H2 5 244 78 85
20 592 60 65
30 763 60 65
SS target 0.5 % O2 5 321 102 106
20 905 91 95
30 1168 91 95
Large vol. Al 10 % H2 5 183 58 63
20 502 51 55
30 513 40 43
Large vol. Al 0.5 % O2 5 228 73 76
20 675 68 71
30 910 71 74
204
Fig. 1. Ratio of the percent theoretical yields (11CH4 /11CO2) for each
of the target configurations as a function of irradiation time. The dia-
mond (e) represents the data for the Al cone target, the square (h) is
for the Ni target, the triangle (n) the SS target, and the circle (s) the
Al cylinder target. All irradiations performed at 20 µA.
beam scattering. However, the improved yields (see
Table 3) still fell far short of the theoretical thick target
yields. Based on evidence that there was carbon-11 activity
remaining in the target after emptying we began investi-
gating different target geometries and materials. We also
used the production of 11CO2 as a check on target efficiency
both in the absolute measure of thick target yield but also
as a relative check as to the likelihood of the nucleogenic
hot atoms interacting with the walls. It should be pointed
out that a single oxygen atom can react with a carbon atom
on the walls to form CO, and subsequently CO2, while the
formation of methane requires four hydrogen atoms. Thus
it is less probable to remove a C-11 atom from the walls in
the hydrogen target mix than for the oxygen mix. To aid in
determining trends in target performance , the ratio of the
percent theoretical yields for 11CH4 to 11CO2 as a function
of irradiation time are plotted in Fig. 1.
The early work of Wolf and colleagues [4, 9212] has
laid the groundwork for interpreting the results presented
in this paper. While most of the experiments performed in
the earlier work involved low beam currents and low pres-
sures, there is a consistent picture that describes the pro-
cesses seen under the present conditions. For example it
has been demonstrated that even with very small amounts
of oxygen (1210 ppm) and at total doses of greater than
1 eV per molecule the radiolytic product from the (p,A) re-
action on nitrogen is CO2. In a like manner for hydrogen
concentration of 5% or greater and doses totaling more than
1 eV the dominant product is methane. Ache and Wolf [9]
also showed that the probability for the 11C-atom reacting
with oxygen is approximately an order of magnitude greater
than the interaction with nitrogen or carbon-hydrogen com-
pounds. In a series of experiments Ache and Wolf [10] also
showed that the recoil hot carbon-11 atom can interact with
the target wall in such a way as to stick, in the absence of
oxygen.
The results comparing the different targets and their pro-
duction of CO2 and CH4 indicate that there are two major
factors affecting the target yields. The first is density re-
K. R. Buckley, J. Huser, T. J. Ruth et al.
duction due to beam heating, which results in a reduction
in yield if the penetration exceeds the thick target stopping
power of the gas [13215, 16]. The other reflects the fate
of the nucleogenic hot 11C-atom.
The production of 11CO2 reflects the status of the target
with respect to density reduction at short irradiation times.
In addition there is less than 10% reduction in the 11CO2
yield with increased irradiation times for all of the targets
tested. When using percent of theoretical yield to measure
production capacity the stainless steel target and the alumi-
num cone target performed the best with yields very near
theoretical. The Ni-plated cone and the large volume alumi-
num performed more poorly (, 80% of theoretical). Hese-
lius et al. [16] showed that for increasing target volume
there is an increase in beam penetration, which can explain
the lower yields for the large volume aluminum target,
however this does not explain why the Ni-plated target per-
formed poorly.
Using the results as illustrated in Fig. 1 it is evident that
all of the target chambers with the exception of the Ni-
plated chamber behave in a very similar fashion, each
showing lower yields for 11CH4 than for 11CO2. From the
early hot-atom experiments described above these results
can be explained by some of the nucleogenic C-11 species
irreversibly interacting with the target chamber walls. The
reported target systems that yield high levels of 11CH4 have
been large volumes (e.g. 40 cm long 3 6 cm diameter) and
operated at pressures exceeding 10 atmospheres and proton
energies above 18 MeV [4, 17]. These conditions favor the
production of CH4 while minimizing the impact of recoil
collisions with the target chamber walls due to the large
diameters which exceeds the beam profile, even after mul-
tiple scattering is taken into account. None of the present
targets had geometries that would prevent recoil 11C-atoms
from interacting with the walls.
In the paper by Helus et al. [6], they observed an energy
dependence for the production of methane. Below about
12 MeV they did not detect any methane. While they did
not report the length of irradiation, the total dose to the
system can be calculated for various irradiation times. For
short irradiation times it appears that their system was be-
low 0.1 eV per molecule, which is consistent with the re-
ported literature where at this level the production of meth-
ane drops off dramatically [4].
Conclusion
There are two major factors affecting the yields from the
various gas targets. The 11CO2 results can be interpreted as
a measure of the production capacity of the targets, which
varies with configuration and material while the yields of
methane reflect the likelihood of recoil hot atoms inter-
acting with the target walls. For geometries that allow mul-
tiple collisions before encountering the wall the methane
yield approaches that of CO2 . However, in situations where
the target chamber approximates the beam shape there is a
high probability of a portion of the generated hot-atom
C-11 species sticking to the walls as seen for the small
targets used in these experiments. Thus, the optimum
design of a gas target should include efficient cooling to
11
C-methane production in small volume, high pressure gas targets
minimize density reduction and sufficient range in the
target volume to allow the in situ hot atom processes to
reach their equilibrium.
Dedication
One of us (TJR) worked with Al Wolf from 1976 until mid-
1980. For the introduction to this field of research I am
forever grateful.
Acknowledgments. The authors wish to thank Drs. Ken Krohn, Jeanne
Link, John Clark and Stefan Zeisler for the many helpful discussions.
We also wish to thank Tamara Hurtado for her help in the fabrication
of the various targets. Support from the Medical Research Council of
Canada and the TRIUMF Life Science Program is gratefully acknowl-
edged.
References
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Appendix
Suppliers of items referred to in the contribution
Havar 2 High Strength Non-Magnetic Alloy (Co 42.5/Cr20/
Ni 13/Fe/W/Mo/Mn) Foil
Goodfellow, Berwyn, PA, USA
Capintec, Inc., Ramsey, NJ, USA
Alltech Associates, Inc., Deerfield, IL 60015, USA
Hewlett-Packard Company, Palo Alto, CA, USA
Porapak (porous polymer), Millipore, Bedford, MA, USA
Reacti-Vial, Pierce Chemical Company, Rockford, IL,
USA
Ascartite, Aldrich Chemical Company, Milwaukee, WI,
USA