Transcript Schmitz F. 1, Monclus M. 1, Van Naemen J. 1, Ekelmans D. 1

11
 C-methyliodide
New approach for
single use system
synthesis in a
Mulleneers E., Van Naemen J., Schmitz F., Monclus M., Kadiata M., Van Gansbeke B., Lorent M., Moray M., Penninckx R.,
Goldman S.
PET/Biomedical Cyclotron Unit, ULB-Hospital Erasme, Route de Lennik, 808, B-1070, Brussels, Belgium
PET data obtained with L-S-11C-methylmethionine is most of the time used for brain tumours imaging1. We are producing L-S11Cmethylmethionine 3 to 4 times per week. The average output of pure L-S-11Cmethylmethionine at EOS is 197+/-52 mCi (n=450) With
this amount of radioactivity we can inject up to 4 patients for whom we are performing exams on two PET scanner (Siemens Exact HR+
and Philips Gemini). We have an uptime on our home made synthesizer of about 97 %. The 3 % failures involve a rescheduling of 15 to
25 patients per year. Most of the time the failure is due to a wrong valve opening or a blocking of the tube or valves despite a careful
cleaning of the synthesizer. To reduce the risk of failure to almost 0 we redesign a single use system according to our past experience on
the Coïncidence prototype and home made dose distributor. Miterhauser et al2 have proposed recently to do the methylation reaction in
a single use system in order to avoid the time consuming preparative HPLC. Our previous experience3,4,5 as well as their work could not
get rid off the 11C-methyliodide production in a “classical” remote controlled system. We have developed the synthesis of 11Cmethyliodide in a single use system expecting with such a device a more reproducible yield. By using the single use system we have
also avoided a complex and time consuming cleaning and sterilizing procedure. We are producing carbon-11 with the classical
14N(p,a)11C nuclear reaction : energy 16 MeV, pressure 30 bars, current 30 µA on a Cyclone-30 supplied by IBA. At the end of the
bombardment, 11CO2 is extracted from the target and is directly trapped at -5°C in a solution of 0.1 M LiAlH4 in THF supplied by ABX (ref :
802.0001). After evaporation of the THF at 95 °C, HI (Aldrich, ref : 210013) previously refluxed on red phosphorous is added, the system is
completely closed and heated during 3 minutes at 105°C. 11C-methyliodide is distilled through KOH pellets (Merck, ref : 1604.0500) and
trapped at -5°C in an ethanol solution (Merck, ref : 1317.80025). The complete process takes 10 minutes and a radiochemical yield EOB of
(48+/-8) % (n=12) has been measured. The single use tubing is an adaptation of a rack of valves supplied by General Electric for FDG
synthesis with the Tracerlab MXfdg (ref : P 5150 ME). Even if this value is not critical for an amino acid injection, the specific activity of
the final L-S-11C-methylmethionine measured is higher than 1 Ci/µmole. This result is in accordance with our previous system. With
such a device, starting from 11CO2 produced in the target, we can synthesize L-S-11C-methylmethionine in a complete sterile single use
system, with good yield.
Scheme 1 : 11C-methyliodide synthesis unit, prototype 1
1. Polysulfone valves
2. Nylon valves
3. Pinch valves with silicon tubing
4. Tracerlab MXfdg reactor
5. Oven
6. Stainless steel needle
7. ABX LiAlH4 vial
8. HI solution
7
N2
8
6
11
C
Table 1 : 11C-methyliodide synthesis unit, distribution of the
radioactivity at EOB
2
1
11CH I
3
CH3 I
3
4
5
OVEN
3
Cool air
min –20°C
REACTOR
WASTE
Scheme 2 : 11C-methyliodide synthesis unit, LiAlH4
vial as a reactor of the unit, prototype 2
1. Polysulfone valves
2. Nylon valves
3. Pinch valves with silicon tubing
4. ABX LiAlH4 vial directly used as an oven
5. Oven
6. HI solution
N2
KOH trap
(%)
13
1
Waste
(%)
59
Run 1
(%)
27
Run 2
34
21
3
41
Run 3
55
25
0
20
Run 4
55
19
1
25
Run 5
52
18
1
28
Run 6
53
18
1
27
Run 7
33
18
9
40
Run 8
55
19
2
25
Run 9
53
18
1
27
Run 10
57
28
2
13
Run 11
47
29
4
20
Run 12
60
10
1
18
Average+/-Std
48+/-8
20+/-4
2+/-1
13+/-8
2
3
Reactor 1
(%)
8
11
C
1
CH3 I
References :
3
3
2
4
5
OVEN
7
Cool air
min –20°C
3
REACTOR
WASTE
1. Becherer A., et al, Eur. J. Nucl. Med. Mol. Imaging, 30, 1561-1567, 2003
2. Miterhauser M., et al, Appl.Radiat.Isot., 62 , 441-445, 2005
3. Schmitz F., et al, J.Nucl.Med. 35, 82P, 1994
4. Schmitz F., et al, Appl.Radiat.Isot., 46, 893-897, 1995
5. Del Fiore G., et al, J.Labell. Compd. Radiopharm., 37, 746-748, 1995