Synthesis of 11C-methionine through gas phase iodination using Synthra MeIPlus synthesis module

Kilian, Krzysztof; Pękal, Anna; Juszczyk, Julia

doi:10.1515/nuka-2016-0007

Abstract

A method of ¹¹C-methionine synthesis using ‘bubbling’ method is presented. ¹¹C-methionine was synthesized via ¹¹C methylation from L-cysteine thiolactone (2 mg) in a 300 μL solution of 2:1:1 (v/v) 1 M NaOH, ethanol, and water at ambient temperature (85°C, 5 min). The radiochemical purity of radiotracer was higher than 99% and enantiomeric purity (L-¹¹C-methionine) was 91.6 ± 0.4%. The final product met the requirements of European Pharmacopoeia monograph. The proposed ¹¹C-methionine synthesis is a reliable tool for routine manufacturing in clinical applications and animal studies.

References

1. Cavuoto, P., & Fenech, M. F. (2012). A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat. Rev., 38, 726–736.10.1016/j.ctrv.2012.01.00422342103
Search in Google Scholar
2. Lodi, F., Malizia, C., Castellucci, P., Cicoria, G., Fanti, S., & Boschi, S. (2012). Synthesis of oncological [¹¹C] radiopharmaceuticals for clinical PET. Nucl. Med. Biol., 39, 447–460.10.1016/j.nucmedbio.2011.10.01622172394
Search in Google Scholar
3. Jacobs, A. H., Thomas, A., Kracht, L. W., Li, H., Dittmar, C., Garlip, G., Galldiks, N., Klein, J. C., Sobesky, J., Hilker, R., Vollmar, S., Herholz, K., Wienhard, K., & Heiss, W. D. (2005). ¹⁸F-fluoro-L-thymidine and ¹¹C-methionine as markers for increased transport and proliferation in brain tumors. J. Nucl. Med., 46, 1948–1958.
Search in Google Scholar
4. Pirotte, B., Goldman, S., Massager, N., David, P., Wikler, D., Vandesteene, A., Salmon, I., Brotchi, J., & Levivier, M. (2004). Comparison of ¹⁸FFDG and ¹¹C methionine for PET-guided stereotactic brain biopsy of gliomas. J. Nucl. Med., 45, 1293–1298.
Search in Google Scholar
5. Pötzi, C., Becherer, A., Marosi, C., Karanikas, G., Szabo, M., Dudczak, R., Kletter, K., & Asenbaum, S. (2007). [¹¹C] Methionine and [¹⁸F] fluorodeoxyglucose PET in the follow-up of glioblastoma multiforme. J. Neurooncol., 84, 305–314.10.1007/s11060-007-9375-617492401
Search in Google Scholar
6. Hasebe, M., Yoshikawa, K., Ohashi, S., Toubaru, S., Kawaguchi, K., Sato, J., Mizoe, J., & Tsujii, H. (2010). A study on the prognostic evaluation of carbon ion radiotherapy for head and neck adenocarcinoma with C-11 methionine PET. Mol. Imaging Biol., 12, 554–562.10.1007/s11307-010-0318-920369300
Search in Google Scholar
7. Matsuo, M., Miwa, K., Tanaka, O., Shinoda, J., Nishibori, H., Tsuge, Y., Yano, H., Iwama, T., Hayashi, S., Hoshi, H., Yamada, J., Kanematsu, M., & Aoyama, H. (2012). Impact of [¹¹C]methionine positron emission tomography for target definition of glioblastoma multiforme in radiation therapy planning. Int. J. Radiat. Oncol. Biol. Phys., 82, 83–89.10.1016/j.ijrobp.2010.09.02021095072
Search in Google Scholar
8. Comar, D., Cartron, J., Maziere, M., & Marazano, C. (1976). Labelling and metabolism of methionine-methyl-¹¹C. Eur. J. Nucl. Med., 1, 11–14.10.1007/BF002532601017425
Search in Google Scholar
9. European Pharmacopoeia, 8th ed. (2014).
Search in Google Scholar
10. Application no. G004503 Supelco: HPLC Analysis of Methionine Enantiomers on Astec® CHIROBIOTIC® T.
Search in Google Scholar
11. Pascali, C., Bogni, A., Iwata, R., Decise, D., Crippa, F., & Bombardieri, E. (1999). High efficiency preparation of L-[S-methyl-¹¹C]methionine by on-column [¹¹C] methylation on C18 Sep-Pak. J. Label. Compd. Radiopharm., 42, 715–724. DOI: 10.1002/(SICI)1099-1344(199908)42:8<;715.
Search in Google Scholar
12. Lodi, F., Rizzello, A., Trespidi, S., Di Pierro, D., Marengo, M., Farsad, M., Fanti, S., Al-Nahhas, A., Rubello, D., & Boschi, S. (2008). Reliability and reproducibility of N-[¹¹C]methyl-choline and L-(S-methyl-[¹¹C])methionine solid-phase synthesis: a useful and suitable method in clinical practice. Nucl. Med. Commun., 29, 736–740.10.1097/MNM.0b013e3282ffb44c18753828
Search in Google Scholar
13. Gómez, V., Gispert, J. D., Amador, V., & Llop, J. (2008). New method for routine production of L-[methyl-¹¹C]methionine: in loop synthesis. J. Label. Compd. Radiopharm., 51, 83–86.10.1002/jlcr.1483
Search in Google Scholar
14. Cheung, M. K., & Ho, C. L. (2009). A simple, versatile, low-cost and remotely operated apparatus for [¹¹C]acetate, [¹¹C]choline, [¹¹C]methionine and [¹¹C] PIB synthesis. Appl. Radiat. Isot., 67, 581–589.10.1016/j.apradiso.2008.08.01819168366
Search in Google Scholar
15. Lodi, F., Trespidi, S., Di Pierro, D., Marengo, M., Farsad, M., Fanti, S., Franchi, R., & Boschi, S. (2007). A simple Tracerlab module modification for automated on-column [¹¹C]methylation and [¹¹C] carboxylation. Appl. Radiat. Isot., 65, 691–695.10.1016/j.apradiso.2006.10.01117158055
Search in Google Scholar
16. Pascali, C., Bogni, A., Cucchi, C., Laera, L., Crispu, O., Maiocchi, G., Crippa, F., & Bombardieri, E. (2011) Detection of additional impurities in the UV-chromatogram of L-[S-methyl-¹¹C]methionine. J. Radioanal. Nucl. Chem., 288, 405–409.
Search in Google Scholar
17. Schmitz, F., Plenevaux, A., Del-Fiore, G., Lemaire, C., Comar, D., & Luxen, A. (1995). Fast routine production of L-[¹¹C-methyl]methionine with Al₂O₃KF. Appl. Radiat. Isot., 46(9), 893–897.10.1016/0969-8043(95)00181-C
Search in Google Scholar
18. Kobayashi, M., Hashimoto, F., Ohe, K., Nadamura, T., Nishi, K., Shikano, N., Nishii, R., Higashi, T., Okazawa, H., & Kawai, K. (2012). Transport mechanism of ¹¹C-labeled L- and D-methionine in human-derived tumor cells. Nucl. Med. Biol., 39(8), 1213–1218.10.1016/j.nucmedbio.2012.06.00622795787
Search in Google Scholar
19. Fukumura, T., Nakao, R., Yamaguchi, M., & Suzuki, K. (2004). Stability of ¹¹C labeled PET radiopharmaceuticals. Appl. Radiat. Isot., 61, 1279–1287.10.1016/j.apradiso.2004.04.01115388122
Search in Google Scholar
20. Bogni, A., Bombardieri, E., Iwata, R., Cadini, C., & Pascali, C. (2003). Stability of L-[S-methyl-¹¹C] methionine solutions. J. Radioanal. Nucl. Chem., 256, 199–203.10.1023/A:1023964712999
Search in Google Scholar

Synthesis of 11C-methionine through gas phase iodination using Synthra MeIPlus synthesis module

Abstract

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