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PET Chemistry pp 289–316Cite as

Synthesis Modules and Automation in F-18 Labeling

  • Conference paper

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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  • DOI: 10.1007/978-3-540-49527-7_11
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References

  • 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 283–305

    Google Scholar 

  • Barrio JR, Huang S-C, Phelps ME (1997) Biological imaging and the molecular basis of dopaminergic diseases. Biochem Pharmacol 54:341–348

    CrossRef  PubMed  CAS  Google Scholar 

  • 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:S334

    Google Scholar 

  • 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 25:343–350

    CrossRef  PubMed  Google Scholar 

  • 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 31:1182–1206

    CAS  Google Scholar 

  • 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]:S212

    Google Scholar 

  • 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 47:61–66

    CrossRef  Google Scholar 

  • Gillings N, Larsen P (2005) A highly flexible modular radiochemistry system. J Labelled Compd Radiopharm 48:S338

    Google Scholar 

  • 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]:S895–897

    Google Scholar 

  • Gomzina NA, Vassiliev DA, Krasikova RN (2002) Optimization of robotic preparation of 2-[18F]fluoro-2-deoxy-D-glucose based on alkali hydrolysis. Radiochemistry 44:366–372

    CrossRef  Google Scholar 

  • 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 61:110–117

    Google Scholar 

  • 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 27:235–238

    PubMed  CAS  Google Scholar 

  • 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 41:49–55

    CAS  Google Scholar 

  • Hamacher K, Coenen HH (2002) Efficient routine production of the 18F-labelled amino acid O-2-18F fluoroethyl-L-tyrosine. Appl Radiat Isot 57:853–856

    CrossRef  PubMed  CAS  Google Scholar 

  • Hess E, Sichler S, Kluge A, Coenen HH (2002) Synthesis of 2-[18F]fluoro-Ltyrosine via regiospecific fluoro-de-stannylation Appl Rad Isot 57:185–191

    CrossRef  CAS  Google Scholar 

  • 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 14:175–183

    CrossRef  Google Scholar 

  • 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 52:87–92

    CrossRef  CAS  Google Scholar 

  • 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 57:347–352

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 29:648–654

    CrossRef  CAS  Google Scholar 

  • 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 227

    Google Scholar 

  • Kiselev MY, Tadino V (2004) US patent application 20040223910, Nov 11

    Google Scholar 

  • 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 31:597–603

    CrossRef  PubMed  CAS  Google Scholar 

  • 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:S376

    CrossRef  CAS  Google Scholar 

  • Kumar P, Wiebe LI, Asikoglu M, Tandon M, McEwan AJ (2002) Microwave-assisted (radio)halogenation of nitroimidazole-based hypoxiamarkers. Appl Radiat Isot 57:697–703

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 40:320–322

    Google Scholar 

  • 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 32:2266–2272

    PubMed  CAS  Google Scholar 

  • 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 42:63–75

    CrossRef  CAS  Google Scholar 

  • 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 45:435–447

    CrossRef  CAS  Google Scholar 

  • Lim JL, Berridge MS (1993) An efficient radiosynthesis of [18F]fluoromisonidazole. Appl Radiat Isot 44:1085–1091

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 42:515–516

    Google Scholar 

  • Nickles RJ, Daube ME, Ruth TJ (1984) An 18O2 target for production of [18F]F2. Appl Rad Isot 35:17–122

    Google Scholar 

  • 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 31:803–809

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 32:899–905

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 240:925–927

    CrossRef  CAS  Google Scholar 

  • 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 62:897–901

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 32:109–116

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 43:331–338

    CrossRef  CAS  Google Scholar 

  • 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 2:233–253

    CrossRef  Google Scholar 

  • Schlyer DJ, Bastos MAV, Alexoff D, Wolf AP (1990) Separation of [18F]fluoride from [18O]water using anion exchange resin. Appl Radiat Isot 41:531–533

    CrossRef  CAS  Google Scholar 

  • 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 25:147–154

    CrossRef  Google Scholar 

  • 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 53:57–67

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 4:1334–1336

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 46:661–668

    CrossRef  CAS  Google Scholar 

  • Tang G, Wang M, Tang X, Gan M, Luo L (2005) Fully automated one-pot synthesis of [18F]fluoromisonidazole. Nucl Med Biol 32:553–558

    CrossRef  PubMed  CAS  Google Scholar 

  • 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 17:273–279

    PubMed  CAS  Google Scholar 

  • 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 51:389–394

    CrossRef  Google Scholar 

  • 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 40:205–212

    CAS  Google Scholar 

  • 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]:S933–934

    Google Scholar 

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Authors and Affiliations

  1. Institute of the Human Brain, Russian Academy of Science, 9 Pavlov Str., 197376, St. Petersburg, Russia

    R. Krasikova

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  1. R. Krasikova
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Editors and Affiliations

  1. Animal Imaging Center — PET, Center for Radiopharmaceutical Science of ETH, PSI and USZ, ETH Hönggerberg D-CHAB, Wolfgang-Pauli Str. 10, 8093, Zürich, Switzerland

    P. A. Schubiger

  2. Corporate Research, Schering AG, Müller Str. 178, 13342, Berlin, Germany

    L. Lehmann & M. Friebe & 

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Krasikova, R. (2007). Synthesis Modules and Automation in F-18 Labeling. In: Schubiger, P.A., Lehmann, L., Friebe, M. (eds) PET Chemistry. Ernst Schering Research Foundation Workshop, vol 64. Springer, Berlin, Heidelberg . https://doi.org/10.1007/978-3-540-49527-7_11

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  • DOI: https://doi.org/10.1007/978-3-540-49527-7_11

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