new approach for 11 c-methyl iodide synthesis in a single use system

1
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- 11 C-methylmethionine is most of the time used for brain tumours imaging 1 . We are producing L-S- 11 Cmethylmethionine 3 to 4 times per week. The average output of pure L-S- 11 Cmethylmethionine 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 al 2 have proposed recently to do the methylation reaction in a single use system in order to avoid the time consuming preparative HPLC. Our previous experience 3,4,5 as well as their work could not get rid off the 11 C-methyliodide production in a “classical” remote controlled system. We have developed the synthesis of 11 C-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 14 N(p,) 11 C nuclear reaction : energy 16 MeV, pressure 30 bars, current 30 µA on a Cyclone-30 supplied by IBA. At the end of the bombardment, 11 CO 2 is extracted from the target and is directly trapped at -5°C in a solution of 0.1 M LiAlH 4 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. 11 C- 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- 11 C-methylmethionine measured is higher than 1 Ci/µmole. This result is in accordance with our previous system. With such a device, starting from 11 CO 2 produced in the target, we can synthesize L-S- 11 C-methylmethionine in a complete sterile single use system, with good yield. New approach for 11 C-methyliodide synthesis in a single use system Scheme 1 : 11 C-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, 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 REACTOR WASTE Cool air min –20°C OVEN N 2 C 11 11 CH I 3 1 2 3 3 3 2 4 5 6 7 8 REACTOR WASTE Cool air min –20°C OVEN CH I 3 3 3 3 2 4 5 N 2 C 11 11 1 8 7 Scheme 2 : 11 C-methyliodide synthesis unit, LiAlH 4 vial as a reactor of the unit, prototype 2 11 CH 3 I (%) 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 : 11 C-methyliodide synthesis unit, distribution of the radioactivity at EOB 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 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

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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 Presentation

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Page 1: New approach for   11 C-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

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