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PET Chemistry pp 289-316 | Cite as

Synthesis Modules and Automation in F-18 Labeling

  • R. Krasikova
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 64)

Abstract

Fast implementation of PET into clinical studies and research has resulted in high demands in the automated modules for the preparation of PET radiopharmaceuticals in a safe and reproducible manner. 18F-labeled radiotracers are of considerable interest due to longer half-life of fluorine-18 allowing remote site application, as demonstrated by [18F]FDG. In this chapter, the state of the art of commercially available modules for [18F]FDG is reviewed with the emphasis on multibatch production of this important radiotracer. Examples are given on the syntheses of other clinically relevant 18F-labeled radiotracers by using existing [18F]FDG synthesizers or with the help of general-purpose [18F]nucleophilic fluorination modules. On-going research and progress in the automation of complex radio labeling procedures followed by development of flexible multipurpose automated apparatus are discussed. The contribution of radiochemists in facilitating automation via introduction of new 18F-labeling techniques and labeling synthons, on-line reactions and purifications etc. is outlined.

Keywords

Positron Emission Tomography Synthesis Module Routine Production Positron Emission Tomography Radiotracer Alkali Hydrolysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Alexoff DL (2003) Automation for the synthesis and application of PET radiopharmaceuticals. In: Welch MJ, Redvanly CS (eds) Handbook of Radiopharmaceuticals. Radiochemistry and Application. Wiley, pp 283–305Google Scholar
  2. Barrio JR, Huang S-C, Phelps ME (1997) Biological imaging and the molecular basis of dopaminergic diseases. Biochem Pharmacol 54:341–348PubMedCrossRefGoogle Scholar
  3. Bonasera TA, Passchier J, Martarello L, James PJ, Lovegrowe JM, Plisson C (2005) GSK’S automated PET radiotracer synthesis system J Labelled Compd Radiopharm 48:S334Google Scholar
  4. Le Bars D, Lemaire C, Ginovart N, Plenevaux A, Aerts J, Brihaye C, Hassoun W, Leviel V, Mekhsian, P, Weissmann D, Pujol JF, Luxen A, Comar D (1998) High-yield radiosynthesis and preliminary in vivo evaluation of p-[18F]MPPF, a fluoro analog of WAY-100635. Nucl Med Biol 25:343–350PubMedCrossRefGoogle Scholar
  5. Couturier O, Luxen A, Chatal J-F, Vuillez J-P, Rigo P, Hustinx R (2004) Fluorinated tracers for imaging cancer with positron emission tomography. Eur J Nucl Med Molec Imag 31:1182–1206Google Scholar
  6. Fedorova OS, Nader M, Keller H-P, Krasikova RN (2003) Development of fully automated module for nucleophilic asymmetric synthesis of 6-[18F]fluoro-L-DOPA. J Label Compds Radiopharm 46[Suppl 1]:S212Google Scholar
  7. Fuchetner F, Steinbach J, Mading P, Johannsen B (1996) Basic hydrolysis of 2-[18F]Fluoro-1,3,4,6-tetra-O-acetyl-d-glucose in the preparation of 2-[18F]Fluoro-2-deoxy-D-glucose. Appl Radiat Isot 47:61–66CrossRefGoogle Scholar
  8. Gillings N, Larsen P (2005) A highly flexible modular radiochemistry system. J Labelled Compd Radiopharm 48:S338Google Scholar
  9. Gomzina NA, Zaitsev VV, Krasikova (2001) Optimization of nucleophilic fluorination step in the synthesis of various compounds labelled with fluorine-18 for their use as PET radiotracers. J Label Compds Radiopharm 44[Suppl 1]:S895–897Google Scholar
  10. Gomzina NA, Vassiliev DA, Krasikova RN (2002) Optimization of robotic preparation of 2-[18F]fluoro-2-deoxy-D-glucose based on alkali hydrolysis. Radiochemistry 44:366–372CrossRefGoogle Scholar
  11. DeGrado TR, Coleman RE, Wang S, Baldwin SW, Orr MD, Robertson CN, Polascik TJ, Price T (2000) Synthesis and evaluation of 18F-labelled choline as an oncological tracer for positron emission tomography: initial findings in prostate cancer. Cancer Res 61:110–117Google Scholar
  12. Hamacher K, Coenen HH, Stöcklin G (1986) Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 27:235–238PubMedGoogle Scholar
  13. Hamacher K, Blessing G, Nebeling B (1990) Computer-aided synthesis (CAS) of no-carrier-added 2-[18F]Fluoro-2-Deoxy-D-Glucose: an efficient automated system for the aminopolyether-supported nucleophilic fluorination. AppRad Isot 41:49–55Google Scholar
  14. Hamacher K, Coenen HH (2002) Efficient routine production of the 18F-labelled amino acid O-2-18F fluoroethyl-L-tyrosine. Appl Radiat Isot 57:853–856PubMedCrossRefGoogle Scholar
  15. Hess E, Sichler S, Kluge A, Coenen HH (2002) Synthesis of 2-[18F]fluoro-Ltyrosine via regiospecific fluoro-de-stannylation Appl Rad Isot 57:185–191CrossRefGoogle Scholar
  16. Ido T, Wan CN, Casella V, Fowler JS, Wolf AP, Rivich M (1977) Labeled 2-deoxy-d-glucose analogs. 18F-labelled 2-deoxy-2-fluoro-d-glucose, 2-deoxy-2-fluoro-d-mannose and 14C-2-deoxy-2-fluoro-d-glucose. J Labelled Compd Radiopharm 14:175–183CrossRefGoogle Scholar
  17. Iwata R, Pascali C, Bogni A., Horvath G, Kovacs Z, Yanai K, Ido T (2000) A new, convenient method for the preparation of 4-[18F]fluorobenzyl halides. Appl Rad Isot 52:87–92CrossRefGoogle Scholar
  18. Iwata R, Pascali C, Bogni A, Furumoto S, Terasaki K, Yanai K (2002) [18F]fluoromethyl triflate, a novel and reactive [18F]fluoromethylating agent: preparation and application to the on-column preparation of [18F]fluorocholine. Appl Radiat Isot 57:347–352PubMedCrossRefGoogle Scholar
  19. Kaim AH, Weber B, Kurrer MO, Westera G, Schweitzer A, Gottschalk J, von Schulthess GK, Buck A (2002) 18F-FDG and 18F-FET uptake in experimental soft tissue infection. Eur J Nucl Med 29:648–654CrossRefGoogle Scholar
  20. Kiselev M, Lemoucheux L, Bouvy C (2004) Production of PET radioisotopes for distribution. Challenges and opportunities. 17th Conference on the Application of Accelerators in Research and Industry (CAARI), USA, Abstract 227Google Scholar
  21. Kiselev MY, Tadino V (2004) US patent application 20040223910, Nov 11Google Scholar
  22. Krasikova RN, Zaitsev VV, Ametamey SM, Kuznetsova OF, Fedorova OS, Mosevich IK, Belokon YN, Vyskocil S, Shatik SV, Nader M, Schubiger PA (2004) Catalytic enantioselective synthesis of 18F-fluorinated alpha-amino acids under phase-transfer conditions using (S)-NOBIN. Nucl Med Biol 31:597–603PubMedCrossRefGoogle Scholar
  23. Krasikova R, Zaitsev V, Truong P, Schou M, Halldin C (2002) Routine production of 4-18F-fluorobenzyl bromide in a remote-controlled synthetic apparatus. Eur J Nucl Med Molec Imag 29:S376CrossRefGoogle Scholar
  24. Kumar P, Wiebe LI, Asikoglu M, Tandon M, McEwan AJ (2002) Microwave-assisted (radio)halogenation of nitroimidazole-based hypoxiamarkers. Appl Radiat Isot 57:697–703PubMedCrossRefGoogle Scholar
  25. Larsen P, Sandell J, Printz G, Johnstrom P, Lundquist K, Nilsson S-O, Stone-Elander S, Swahn CG, Soderholm P, Thorell J-O, Halldin C (1997) A heap-filtered air controlled automated system for [11C]methyl triflate production and methylation of PET radioligands. J Label Compds Radiopharm 40:320–322Google Scholar
  26. Lemaire C, Cantineau R, Guillaume M, Plenevaux A, Christiaens L (1991) Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats. J Nucl Med 32:2266–2272PubMedGoogle Scholar
  27. Lemaire C, Plenevaux A, Aerts G, Del Fiore G, Brihaye C, Le Bars D, Comar D and Luxen A (1999) Solid phase extraction — an alternative to the use of rotary evaporators for solvent removal in the rapid formulation of PET radiopharmaceuticals. J Labelled Compds Radiopharm 42:63–75CrossRefGoogle Scholar
  28. Lemaire C, Damhaut Ph, Lauricella B, Mosdzianowski C, Morelle J-L, Plenevaux A, Brihaye C, Luxen A (2002) Fast [18F]FDG synthesis by alkaline hydrolysis on a low polarity solid phase support. J Labelled Compd Radiopharm 45:435–447CrossRefGoogle Scholar
  29. Lim JL, Berridge MS (1993) An efficient radiosynthesis of [18F]fluoromisonidazole. Appl Radiat Isot 44:1085–1091PubMedCrossRefGoogle Scholar
  30. Mosdzianowski C, Lemaire C, Lauricella B, Aerts J, Morelle J-L, Gobert F (1999) Routine and multi-curie level productions of [18F]FDG using an alkaline hydrolysis on solid support. J Labelled Compd Radiopharm 42:515–516Google Scholar
  31. Nickles RJ, Daube ME, Ruth TJ (1984) An 18O2 target for production of [18F]F2. Appl Rad Isot 35:17–122Google Scholar
  32. Oh SJ, Mosdzianowski C, Chi DY, Kim JY, Kang SH, Ryu JS, Yeo JS, Moon DH (2004) Fully automated synthesis system of 3′-deoxy-3′-[18F]fluorothymidine. Nucl Med Biol 31:803–809PubMedCrossRefGoogle Scholar
  33. Oh SJ, Chi DY, Mosdzianowski C, Kim JY, Gil HS, Kang SH, Ryu JS, Moon DH (2005) Fully automated synthesis of [18F]fluoromisonidazole using a conventional [18F]FDG module. Nucl Med Biol 32:899–905PubMedCrossRefGoogle Scholar
  34. Patt M, Kuntzsch M, Machulla HJ (1999) Preparation of fluoromisonidazole by nucleophilic substitution on THP-protected precursor: yield dependence on reaction parameters. J Radioanal Nucl Chem 240:925–927CrossRefGoogle Scholar
  35. Reischl G, Ehrlichmann W, Bieg C, Solbach C, Kumar P, Wiebe LI, Machulla HJ (2005) Preparation of the hypoxia imaging PET tracer [18F]FAZA: reaction parameters and automation. Appl Radiat Isot 62:897–901PubMedCrossRefGoogle Scholar
  36. Ryzhikov NN, Seneca N, Krasikova RN, Gomzina NA, Shchukin E, Fedorova OS, Vassiliev DA, Gulyás B, Hall H, Savic I, Halldin C (2005) Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography. Nucl Med Biol 32:109–116PubMedCrossRefGoogle Scholar
  37. Sandell J, Langer O, Larsen P, Dolle F, Vaufrey F, Demphel S, Crouzel C, Halldin C (2000) improved specific radioactivity of the PET radioligand [11C]FLB by use of the GE medical systems PETTrace MeI Microlab. J Labelled Compds Radiopharm 43:331–338CrossRefGoogle Scholar
  38. Satyamurthy N, Phelps ME, Barrio JR (1999) Electronic generators for the production of positron-emitter labelled radiopharmaceuticals: Where would PET be without them? Clin Posit Imag 2:233–253CrossRefGoogle Scholar
  39. Schlyer DJ, Bastos MAV, Alexoff D, Wolf AP (1990) Separation of [18F]fluoride from [18O]water using anion exchange resin. Appl Radiat Isot 41:531–533CrossRefGoogle Scholar
  40. Schiue CY, Schiue GG, Mozley PD, Kung M, Zhuang Z, Kimn HJ (1997) p-[18F]MPPF: A potential radioligand for PET studies of 5-HT1A receptor in humans. Synapse 25:147–154CrossRefGoogle Scholar
  41. Schou M, Halldin C, Sovago J, Pike VW, Hall H, Gulyas B, Mozley PD, Dobson D, Shchukin E, Innis RB, Farde L (2004) PET evaluation of novel radiofluorinated reboxetine analogs as norepinephrine transporter probes in the monkey brain Synapse 53:57–67PubMedCrossRefGoogle Scholar
  42. Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM (1998) Imaging proliferation in vivo with [18F]FLT and positron emission tomography Nature Med 4:1334–1336PubMedCrossRefGoogle Scholar
  43. Tang G, Tang X, Wang M, Luo L, Gan M, Huang Z (2003) Automated commercial synthesis system for preparation of O-(2-[18F]fluoroethyl)-L-tyrosine by direct nucleophilic displacement on a resin column. J Label Compd Radiopharm 46:661–668CrossRefGoogle Scholar
  44. Tang G, Wang M, Tang X, Gan M, Luo L (2005) Fully automated one-pot synthesis of [18F]fluoromisonidazole. Nucl Med Biol 32:553–558PubMedCrossRefGoogle Scholar
  45. Toorongian SA. Mulholland K, Jewett DM, Bachelor MA, Kilbourn MR (1990). Routine production of 2-deoxy-2-[18F]fluoro-D-glucose by direct nucleophilic exchange on a quaternary 4-aminopyridinium resin. Int J Rad Appl Instrum B 17:273–279PubMedGoogle Scholar
  46. de Vries EFJ, Luurstema G, Brussermann M, Elsinga PH, Vaalburg W (1999) Fully automated synthesis module for the high yield one-pot preparation of 6-[18F]fluoro-L-DOPA. Appl Rad Isot 51:389–394CrossRefGoogle Scholar
  47. Wester H, Herz M, Weber W, Heiss P, Senekovitsch-Schmidtke R, Schswaiger M, Stocklin G (1999) Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. J NuclMed 40:205–212Google Scholar
  48. Westera G, Patt JT, Sjoberg C-O, Schmidt N, Schuboger PA (1999) A versatile synthesis apparatus for easy automation. J Label Compds Radiopharm 42[Suppl 1]:S933–934Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • R. Krasikova
    • 1
  1. 1.Institute of the Human BrainRussian Academy of ScienceSt. PetersburgRussia

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