new approach for 11 c-methyl iodide synthesis in a single use system
DESCRIPTION
N 2. 8. 1. CH I. CH I. 3. 3. 11. 11. C. C. New approach for 11 C-methyl iodide synthesis in a single use system. - PowerPoint PPT PresentationTRANSCRIPT
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-methylmethionine is most of the time used for brain tumours imaging1. We are producing L-S-11Cmethylmethionine 3 to 4 times per week. The average output of pure L-S-11Cmethylmethionine 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-methyliodide production in a “classical” remote controlled system. We have developed the synthesis of 11C-methyliodide
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,)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-methyliodide 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-
methylmethionine 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-methylmethionine in a complete sterile single use system, with
good yield.
New approach for 11C-methyliodide synthesis in a single use system
Scheme 1 : 11C-methyliodide synthesis unit, prototype 1
References :
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, 20053. Schmitz F., et al, J.Nucl.Med. 35, 82P, 19944. Schmitz F., et al, Appl.Radiat.Isot., 46, 893-897, 19955. Del Fiore G., et al, J.Labell. Compd. Radiopharm., 37, 746-748, 1995
REACTOR WASTE
Cool airmin –20°C
OVEN
NN22
CC1111
CH I3
1
2
33
3
2
4
5
6
78
REACTOR WASTE
Cool airmin –20°C
OVEN
CH I3
33
3
2
4
5
NN22
CC1111
1
8
7
Scheme 2 : 11C-methyliodide synthesis unit, LiAlH4 vial as a reactor of the unit, prototype 2
11CH3I
(%)
Reactor 1 (%)
KOH trap (%)
Waste
(%)
Run 1 27 13 1 59
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
Table 1 : 11C-methyliodide synthesis unit, distribution of the radioactivity at EOB
1. Polysulfone valves 2. Nylon valves3. Pinch valves with silicon tubing4. Tracerlab MXfdg reactor5. Oven6. Stainless steel needle7. ABX LiAlH4 vial8. HI solution
1. Polysulfone valves 2. Nylon valves3. Pinch valves with silicon tubing4. ABX LiAlH4 vial directly used as an oven5. Oven6. HI solution