New approach for  11 C-methyl  iodide synthesis in a single use system

1. N2 8 1 CH I CH I 3 3 11 11 C C New approach for 11C-methyliodide synthesis in a single use system 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 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 PET data obtained with L-S-11C-methylmethionine is most of the time used for brain tumours imaging1. We are producing L-S-11Cmethyl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 11C-methyl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. Table 1 : 11C-methyliodide synthesis unit, distribution of the radioactivity at EOB 6 2 1 3 2 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 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, 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 3 2 3 4 5 OVEN 7 3 Cool air min –20°C REACTOR WASTE