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Micro-reactors for PET Tracer Labeling

  • Conference paper
PET Chemistry

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 64))

Abstract

Miniaturization of PET radiosynthesis devices (micro-reactors or microfluidic systems) is an emerging area that has the potential to deliver many advantages, such as more efficient use of hot-cell space for production of multiple radiotracers; use of less non-radioactive precursor for saving precious material and a reduced separation challenge; highly controlled, reproducible and reliable radiotracer production; and cheap, interchangeable, disposable and quality-assured radiochemistry processors. Several ‘proof of principle’ examples along with basics of micro-reactor flow control, mixing principle and design, and device fabrication are discussed in this chapter.

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References

  • Auroux PA, Iossifidis D, Reyes DR, Manz A(2002) Micro total analysis systems 2. Analytical standard operations and applications. Anal Chem 74:2637–2652

    Article  PubMed  CAS  Google Scholar 

  • Becker H, Locascio LE (2002) Polymer microfluidic devices. Talanta 56:267–287

    Article  CAS  PubMed  Google Scholar 

  • Block D, Coenen HH, Stöcklin G (1987) The NCA nucleophilic F-18 fluorination of 1,n-disubstituted alkanes as fluoroalkylation agents. J Label Compd Radiopharm 24:1029–1042

    Article  CAS  Google Scholar 

  • Bolton R (2001) Isotopic methylation. J Label Compd Radiopharm 44:701–736

    Article  CAS  Google Scholar 

  • Brady F, Luthra SK, Gillies JM, Geffery NT (2003) Use of microfabricated devices. PCT WO 03/078358 A2

    Google Scholar 

  • Burns HD, Hamill TH, Eng WS, Francis B, Fioranti C, Gibson RE (1999) Positron emission tomography neuroreceptor imaging as a tool in drug discovery, research and development. Curr Opin Chem Biol 2:388–394

    Article  Google Scholar 

  • Comar D (1995) PET for drug development and evaluation. Dev Nucl Med No 26. Kluwer Academic Publishers, Dordrecht

    Google Scholar 

  • Crouzel C, Långström B, Pike VW, Coenen HH (1987) Recommendations for a practical production of [11C]methyl-iodide. Appl Radiat Isot Intl J Appl Instrument Part A 38:601–603

    Article  CAS  Google Scholar 

  • Cullen CJ, Wootton RCR, de Mello AJ (2004) Microfluidic systems for high throughput and combinatorial chemistry. Curr Opin Drug Disc 7:798–806

    CAS  Google Scholar 

  • DeWitt SH (1999) Microreactors for chemical synthesis. Curr Opin Chem Biol 3:350–356

    Article  PubMed  CAS  Google Scholar 

  • Ehrfeld W, Hessel V, Löwe H (2000) Microreactors — new technology for modern chemistry. Wiley-VCH, Weinheim

    Google Scholar 

  • Elsinga PH (2002) Radiopharmaceutical chemistry for positron emission tomography. Methods 27: 208–217

    Article  PubMed  CAS  Google Scholar 

  • Feng XZ, Haswell SJ, Watts P (2004) Organic synthesis in micro reactors. Curr Top Med Chem 4:707–727

    Article  PubMed  CAS  Google Scholar 

  • Fiorini GS, Chiu DT (2005) Disposable microfluidic devices: fabrication, function and application. BioTechniques 38:429–446

    Article  PubMed  CAS  Google Scholar 

  • Fletcher PD, Haswell SJ, Pombo-Villar E, Warrington BH, Watts P, Wong SYF, Zhang X (2002) Micro-reactors: principles and applications in organic synthesis. Tetrahedron 58:4735–4757

    Article  CAS  Google Scholar 

  • Fowler JS, Ido T (2002) Initial and subsequent approach for the synthesis of [18F]FDG. Seminars Nucl Med 32:6–12

    Article  Google Scholar 

  • Fowler JS, Wolf AP (1982) The synthesis of carbon-11, fluorine-18 and nitrogen-13 labeled radiotracers for biomedical applications. Technical Information Center, US Department of Energy, Washington DC

    Google Scholar 

  • Fowler JS, Wolf AP (1997) Working against time: rapid radiotracer synthesis and imaging the human brain. Acc Chem Res 30:181–188

    Article  CAS  Google Scholar 

  • Gawron AJ, Martin RS, Lunte SM (2001) Microchip electrophoretic separation systems for biomedical and pharmaceutical analysis. Eur J Pharm Sci 14:1–12

    Article  PubMed  CAS  Google Scholar 

  • Ghosal S (2004) Fluid mechanics of electroosmotic flow and its effect on band broadening in capillary electrophoresis. Electrophoresis 25:214–228

    Article  PubMed  CAS  Google Scholar 

  • Gillies JM, Prenant C, Zweit J (2005) Radiolabeling of PET and SPECT radiopharmaceuticals using microfluidic reactor (abstract). J Nucl Med 46[Suppl 2]:31P

    Google Scholar 

  • Gillies JM, Prenant C, Chimon GN, Smethurst GJ, Perrie W, Hamblett I, Dekker B, Zweit J (2006) Microfluidic reactor for the radiosynthesis of PET radiotracers. Appl Radiat Isot 64:325–332

    Article  PubMed  CAS  Google Scholar 

  • Halldin C, Stone-Elander S, Farde L, Ehrin E, Fasth KJ, Långström B, Sedvall G (1986) Preparation of C-11 labeled SCH 23390 for the in vivo study of dopamineD-1 receptors using positron emission tomography 37:1039–1043

    CAS  Google Scholar 

  • Harrison DJ, Fluri K, Seiler K, Fan ZH, Effenhauser CS, Manz A (1993) Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip. Science 261:895–897

    Article  CAS  PubMed  Google Scholar 

  • Huikko K, Kostiainen R, Kotiaho T (2003) Introduction to micro-analytical systems: bioanalytical and pharmaceutical applications. Eur J Pharm Sci 20:149–171

    Article  PubMed  CAS  Google Scholar 

  • Iwata R (2004) Reference book for PET radiopharmaceuticals. CYRIC, Tohoku. Available at: http://kakuyaku.cyric.tohoku.ac.jp/public/preface2004.html

    Google Scholar 

  • Jähnisch K, Hessel V, Löwe H, Baerns M (2004) Chemistry in microstructured reactors. Angew Chem Int Ed 43:406–446

    Article  CAS  Google Scholar 

  • Jakeway SC, de Mello AJ, Russell EL (2000) Miniaturized total analysis systems for biological analysis. Fresenius J Anal Chem 366:525–539

    Article  PubMed  CAS  Google Scholar 

  • Jeffery NT, Luthra SK, Manz A, de Mello A, Wootton R, Brady F (2004) Radiochemistry on microfabricated devices: proof of principle (abstract). J Nucl Med 45[Suppl 2]:51P

    Google Scholar 

  • Johnson TJ, Ross D, Locascio LE (2002) Rapid microfluidic mixing. Anal Chem 74:45–51

    Article  PubMed  CAS  Google Scholar 

  • Larsen P, Ulin J, Dahlstrøm K, Jensen M, (1997) Synthesis of [11C]iodomethane by iodination of [11C]methane. Appl Radiat Isot 48:153–157

    Article  CAS  Google Scholar 

  • Laser DJ, Santiago (2004) A review of micropumps. J Micromech Microeng 14:R35–64

    Article  Google Scholar 

  • Lee CC, Sui GD, Elizarov A, Shu CJ, Shin YS, Dooley AN, Huang J, Daridon A, Wyatt P, Stout D, Kolb HC, Witte ON, Satyamurthy N, Heath JR, Phelps ME, Quake SR, Tseng HR (2005) Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science 310:1793–1796

    Article  PubMed  CAS  Google Scholar 

  • Link JM, Krohn KA, Clark JC (1997) Production of [11C]CH3I by single pass reaction of [11C]CH4 with I2. Nucl Med Biol 24:93–97

    Article  PubMed  CAS  Google Scholar 

  • Liow E, O’Brien A, Luthra SK, Brady F, Steel C (2005) Preliminary studies of conducting high level production radiosyntheses using microfluidic devices (abstract). J Label Compd Radiopharm 48[Suppl 1]:S28

    Google Scholar 

  • Liu RH, Lenigk R, Druyor-Sanchez RL, Yang J, Grodzinski (2003) Hybridization enhancement using cavitation microstreaming. Anal Chem 75:1911–1917

    Article  PubMed  CAS  Google Scholar 

  • Lu SY, Watts P, Chin FT, Hong J, Musachio JL, Briard E, Pike VW (2004a) Syntheses of 11C-and 18F-labeled carboxylic esters within a hydrodynamically-driven micro-reactor. Lab Chip 4:523–525

    Article  PubMed  CAS  Google Scholar 

  • Lu SY, Watts P, Chin FT, Hong J, Musachio JL, Haswell SJ, Pike VW (2004b) Exploration of a micro-reactor for the synthesis of NCA 11C-and 18Flabelled carboxylic esters (abstract). Eur J Nucl Med 31[Suppl 2]:S248

    Google Scholar 

  • Lucignani G (2006) Pivotal role of nanotechnologies and biotechnologies for molecular imaging and therapy. Eur J Nucl Med Mol Imaging 33:849–851

    Article  PubMed  Google Scholar 

  • McDonald JC, Whitesides GM (2002) Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. Acc Chem Res 35:491–499

    Article  PubMed  CAS  Google Scholar 

  • Nagasawa H, Aoki N, Mae K (2005) Design of a new micromixer for instant mixing based on the collision of micro segments. Chem Eng Technol 28:324–330

    Article  CAS  Google Scholar 

  • Nguyen NT, Huang XY, Toh KC (2002) MEMS — micropumps: a review. J Fluids Eng 124:384–392

    Article  Google Scholar 

  • Nguyen NT, Wu ZG (2005) Micromixers — a review. J Micromech Microeng 15:R1–R16

    Article  Google Scholar 

  • Okubo T, Yoshikawa R, Chaki S, Okuyama S, Nakazato A (2004) Design, synthesis and structure-affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands. Bioorg Med Chem 12:423–428

    Article  PubMed  CAS  Google Scholar 

  • Osman S, Rowlinson-Busza G, Luthra SK, Aboagye EO, Brown GD, Brady F, Myers R, Gamage SA, Denny WA, Baguley BC, Price PM (2001) Comparative biodistribution and metabolism of carbon-11-labeled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide and DNA-intercalating analogues. Cancer Res 61:2935–2944

    PubMed  CAS  Google Scholar 

  • Phelps ME (1991) PET-A biological imaging technique. Neurochem Res 16:929–940

    Article  PubMed  CAS  Google Scholar 

  • Phelps ME (2000) Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci USA 97:9226–9233

    Article  PubMed  CAS  Google Scholar 

  • Phelps ME, Mazziotta JC (1985) Positron emission tomography: human brain function and biochemistry. Science 228:799–809

    Article  PubMed  CAS  Google Scholar 

  • Pike VW (1997) The status of PET radiochemistry for drug development and evaluation. Drug Information J 31:997–1013

    Google Scholar 

  • Ratner DM, Murphy ER, Jhunjhunwala M, Snyder DA, Jensen KF, Seeberger PH (2005) Microreactor based reaction optimisation in organic chemistry — glycosylation as a challenge. Chem Commun 578–580

    Google Scholar 

  • Reyes DR, Iossifidis D, Auroux PA, Manz A (2002) Micro total analysis systems 1. Introduction, theory, and technology. Anal Chem 74:2623–2636

    Article  PubMed  CAS  Google Scholar 

  • Schwalbe T, Autze V, Hohmann M, Stirner W (2004) Novel innovation systems for a cellular approach to continuous process chemistry from discovery to market. Org Proc Res Dev 8:440–454

    Article  CAS  Google Scholar 

  • Seong GH, Crooks RH (2002) Efficient mixing and reactions within microfluidic channels using microbead-supported catalysts. J Am Chem Soc 124:13360–13361

    Article  PubMed  CAS  Google Scholar 

  • Stöcklin G, Pike VW(1993) Radiopharmaceuticals for positron emission tomography: methodological aspects. Dev Nucl Med No 24. Kluwer Academic Publishers, Dordrecht

    Google Scholar 

  • Stroock AD, Whitesides GM (2003) Controlling flows in microchannels with patterned surface charge and topography. Acc Chem Res 36:597–604

    Article  PubMed  CAS  Google Scholar 

  • Studenov AR, Berridge MS (2001) Synthesis and properties of 18F-labeled potential myocardial blood flow tracers. Nucl Med Biol 28:683–693

    Article  PubMed  CAS  Google Scholar 

  • Vilkner T, Janasek D, Manz A (2004) Micro total analysis systems — recent developments. Anal Chem 76:3373–3385

    Article  PubMed  CAS  Google Scholar 

  • Wagner HN (1991) Clinical PET — its time has come. J Nucl Med 32:561–564

    PubMed  Google Scholar 

  • Watts P, Haswell SJ (2003) Microfluidics combinatorial chemistry. Curr Opin Chem Biol 7:380–387

    Article  PubMed  CAS  Google Scholar 

  • Welch MJ, Redvanly CS (2003) Handbook of radiopharmaceuticals, radiochemistry and applications. John Wiley & Son Ltd, Chichester

    Google Scholar 

  • Woias P (2005) Micropumps — past, progress and future prospects. Sen Actuat B105:28–38

    Article  Google Scholar 

  • Yoshida JI (2005) Flash chemistry using electrochemical method and microsystems. Chem Commun 4509–4516

    Google Scholar 

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Author information

Authors and Affiliations

  1. PET Radiopharmaceutical Sciences, Molecular Imaging Branch, National Institute of Mental Health, NIH, Building 10, Room B3C346, 10 Center Drive, MSC1003, Bethesda, MA, 20892-1003, USA

    S. Y. Lu & V. W. Pike

Authors
  1. S. Y. Lu
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  2. V. W. Pike
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Editor information

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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Lu, S.Y., Pike, V.W. (2007). Micro-reactors for PET Tracer 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_10

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  • DOI: https://doi.org/10.1007/978-3-540-49527-7_10

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-32623-6

  • Online ISBN: 978-3-540-49527-7

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