Historical and radiopharmaceutical relevance of [18F]FDG

A Commentary to this article is available


The 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) is the most well-known radiopharmaceutical positron emitter, in both clinical and preclinical fields. Based on a literature review of research from the last 40 years, this paper focuses on the most important aspects of [18F]FDG production and its evolution over time. Possible future perspectives of this important radiotracer are also discussed.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Scheme 1
Scheme 2
Fig. 4
Fig. 5
Fig. 6


  1. 1.

    Jones T, Townsend D (2017) History and future technical innovation in positron emission tomography. J Med Imaging 4(1):011013

    Article  Google Scholar 

  2. 2.

    https://www.nirs.qst.go.jp/research/division/mic/db2/. Accessed 19 Mar 2019

  3. 3.

    Iwata R (2004) Reference book for PET radiopharmaceuticals. http://kakuyaku.cyric.tohoku.ac.jp/public/preface2004.html. Accessed 19 Mar 2019

  4. 4.

    International Atomic Energy Agency (2018) Quality control in the production of radiopharmaceuticals. IAEA-TECDOC-1856, Vienna

  5. 5.

    Kuhl DE, Phelps ME, Hoffman EJ, Robinson GD Jr, Mac-Donald NS (1977) Initial clinical experience with 18F-2-fluoro-2-deoxy-d-glucose for determination of local cerebral glucose utilization by emission computed tomography [abstract]. Acta Neurol Scand 56(suppl 64):192–193

    Google Scholar 

  6. 6.

    Reivich M, Kuhl D, Wolf AP, Greenberg J, Phelps M, Ido T, Casella V, Hoffman E, Alavi A, Sokoloff L (1979) Circ Res 44:127–137

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Sokoloff L, Reivich M, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetised albino rat. J Neurochem 28:897–916

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  8. 8.

    Weber WA (2006) Positron emission tomography as an imaging biomarker. J Clin Oncol 24(20):3282–3292

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Gallamini A, Zwarthoed C, Borra A (2014) Positron emission tomography (PET) in oncology. Cancers 6:1821–1889

    PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    https://www.ncbi.nlm.nih.gov/pubmed. Accessed 29 Mar 2019

  11. 11.

    Gallagher BM, Ansari A, Atkins H, Casella V, Christman DR, Fowler JS, Ldo T, MacGregor RR, Som P, Wan CN, Wolf AP, Kuhl DE, Reivich M (1977) Radiopharmaceuticals XXVII. 18F-labeled 2-deoxy-2-fluoro-d-glucose as a radiopharmaceutical for measuring regional myocardial glucose metabolism in vivo: tissue distribution and imaging studies in animals. J Nucl Med 18:990–996

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Phelps ME (1977) Emission computed tomography. Semin Nucl Med 7(4):337–365

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Phelps ME (1977) What is the purpose of emission computed tomography in nuclear medicine? J Nucl Med 18:399–402

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, Casella V, Fowler J, Gallagher B, Hoffman E, Alavi A, Sokoloff L (1977) [Abstract] American Neurological Association meeting

  15. 15.

    Phelps ME, Hoffman EJ, Selin C, Huang SC, Robinson G, MacDonald N, DE SchelbertH Kuhl (1978) Investigation of [18F]2-fluoro-2-deoxy-glucose for the measure of myocardial glucose metabolism. J Nucl Med 19:1311–1319

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-d-glucose: validation of method. Ann Neurol 6:371–388

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  17. 17.

    Pacák J, Točík Z, Černý M (1969) Synthesis of 2-deoxy-2-fluoro-d-glucose. Chem Commun 77

  18. 18.

    Adamson J, Foster AB (1969) 2-Deoxy-2-fluoro-d-glucose. Chem Commun 6:309–310

    Article  Google Scholar 

  19. 19.

    Adamson J, Foster AB (1970) Fluorinated carbohydrates part III’. 2-Deoxy-2-fluoro-d-glucose and 2-deoxy-2-fluoro-d-mannose. Carbohyd Res 15:351–359

    CAS  Article  Google Scholar 

  20. 20.

    Ido T, Wan C-N, Fowler JS, Wolf AP (1977) Fluorination with F2. A convenient synthesis of 2-deoxy-2-fluoro-d-glucose. J Org Chem 42(13):2341–2342

    CAS  Article  Google Scholar 

  21. 21.

    Fowler JS, Finn RD, Lambrecht RM, Wolf AP (1973) The synthesis of 18F-5-fluorouracil. J Nucl Med 14:63–64

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ido T, Wan C-N, Casella V, Fowler JS, Wolf AP (1978) Labeled 2-deoxy-d-glucose analogs. 18F-labeled 2-deoxy-2-fluoro-d-glucose, 2-deoxy-2-fluoro-d-mannose and 14C-2-deoxy-2-fluoro-d-glucose. J Label Compd Radiopharm 14(2):175–183

    CAS  Article  Google Scholar 

  23. 23.

    Yu S (2006) Review of 18F-FDG synthesis and quality control. Biomed Imaging Interv J 2(4):e57

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Fowler JS, Ido T (2002) Initial and subsequent approach for the synthesis of 18FDG. Semin Nucl Med 22(1):6–12

    Article  Google Scholar 

  25. 25.

    Shiue C-Y, Salvadori PA, Wolf AP, Fowler JS, MacGregor RR (1982) A new improved synthesis of 2-deoxy-2-[18F]fluoro-d-glucose from 18F-labeled acetyl hypofluorite. J Nucl Med 23:899–903

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Adam MJ (1982) A rapid, stereoselective, high yielding synthesis of 2-deoxy-2-fluoro-dhexopyranoses: reaction of glycols with acetyl hypofluorite. J Chem Soc Chem Commun 13:730–732

    Article  Google Scholar 

  27. 27.

    Diksic M, Jolly D (1983) New high-yield synthesis of 18F-labeled 2-deoxy-2-fluoro-d-glucose. Int J Appl Radiat Isot 34:893–896

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Ehrenkaufer RE, Potocki JF, Jewett DM (1984) Simple synthesis of F-18-labeled 2-fluoro-2-deoxy-d-glucose: concise communication. J Nucl Med 25:333–337

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Jewett DM, Potocki JF, Ehrenkaufer RE (1984) A gas-solid phase microchemical method for the synthesis of acetyl hypofluorite. J Fluor Chem 24:477–484

    CAS  Article  Google Scholar 

  30. 30.

    Shiue C-Y, To KC, Wolf AP (1983) A rapid synthesis of 2-deoxy-2-fluoro-d-glucose from xenon difluoride suitable for labeling with 18F. J Label Compd Rad 20:157–162

    CAS  Article  Google Scholar 

  31. 31.

    Sood S, Firnau G, Gatnett ES (1983) Radiofluorination with xenon difluoride. Int JAppl Radiat Isot 34:743–745

    CAS  Article  Google Scholar 

  32. 32.

    Levy S, Ehnaleh D, Livni E (1982) A new method using anhydrous [18F]fluoride to radiolabel 2-[18F]fluoro-2-deoxy-d-glucose. J Nucl Med 23:918–922

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Levy S, Livni E, Ehnaleh D, Curatolo WJ (1982) Direct displacement with anhydrous fluoride of the C-2 trifluoromethanesulfonate of methyl 4,6-O-benzylidene-3-O-methyl-2-0-trifluoromethylsulphonyl-β-D-mannoside. J Chem Soc Chem Commun 17:972–973

    Article  Google Scholar 

  34. 34.

    Tewson TJ (1983) Cyclic sulfur esters as substrates for nucleophilic substitution. A new synthesis of 2-deoxy-2-fluoro-d-glucose. J Org Chem 48:3507–3510

    CAS  Article  Google Scholar 

  35. 35.

    Tewson TJ (1983) Synthesis of no-carrier-added fluorine-18 2-fluoro-2-deoxy-d-glucose. J Nucl Med 24:718–721

    CAS  PubMed  Google Scholar 

  36. 36.

    Tewson TJ, Soderlind M (1985) I-Propenyl-4,6-O-benzylidene-β-mannopyranoside-2,3-cyclic sulfate: a new substrate for the synthesis of [F-18]-2-deoxy-2-fluoroglucose [abstract]. J Nucl Med 26:P129

    Google Scholar 

  37. 37.

    Szarek W, Hay GW, Perlmutter MM (1982) A rapid stereospecific synthesis of 2-deoxy-3-fluoro-d-glucose using fluoride ion. J Chem Soc Chem Commun 21:1253–1254

    Article  Google Scholar 

  38. 38.

    Beeley PA, Szarek WA, Hay GW, Perlrnutter MM (1984) A synthesis of 2-deoxy-2-[18F]fluoro-d-glucose using accelerator-produced 18F-fluoride ion generated in a water target. Can J Chem 62:2709–2711

    CAS  Article  Google Scholar 

  39. 39.

    Hamacher K, Coenen HH, Stocklin G (1986) Efficient stereospecific synthesis of NCA 2-[18F]fluoro-2-deoxy-d-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 27:235–238

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Toorongian SA, Mulholland GK, Jewett DM, Bachelor MA, Kilbourn MR (1990) Routine production of 2-deoxy-2-[18F]fluoro-d-glucose by direct nucleophilic exchange on a quaternary4-aminopyridinium resin. Int J Rad Appl Instrum B 17:273–279

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    Füchtner 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(I):61–66

    Article  Google Scholar 

  42. 42.

    Aerts J, Ballinger JR, Behe M, Decristoforo C, Elsinga PH, Faivre-Chauvet F, Mindt TL, Kolenc Peitl P, Todde SC, Koziorowskik J (2014) Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective. J Label Compd Radiopharm 57:615–620

    CAS  Article  Google Scholar 

  43. 43.

    Barrio JA, MacDonald NS, Robinson GD Jr, Najafi A, Cook JS, Kuhl DE (1981) Remote, semiautomated production of F-18-labeled 2-deoxy-2-fluoro-d-glucose. J Nucl Med 22:372–375

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Iwata R, Ido T, Takahashi T, Monma M (1984) Automated synthesis system for production of 2-deoxy-2-[18F]fluoro-d-glucose with computer control. Int J Appl Radiat Isot 35(6):445–454

    CAS  Article  Google Scholar 

  45. 45.

    Oh S, Nam K, Lee KC, Ghergherehchi M, Kim B, Kim JY, Song HS, Chai JS (2018) Development of a disposable kit with fully automatic self-shielding reactor for [18F]FDG synthesis. Appl Radiat Isot 131:23–29

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Vallabhajosula S (2009) Molecular imaging. Radiopharmaceuticals for PET and SPECT. Springer, Berlin, p 2009

    Google Scholar 

  47. 47.

    Petroni D, Poli M, Campisi L, Salvadori PA, Menichetti L (2012) Implementation of good manufacturing practice in small-volume production of [18F]FDG: a case report of performance measurements. J Radioanal Nucl Chem 293:757–762

    CAS  Article  Google Scholar 

  48. 48.

    Krasikowa R (2007) Synthesis modules and automation in F-18 labeling. In: Schubiger PA, Lehmann L, Friebe M (eds) PET chemistry: the driving force in molecular imaging. Springer, Heidelberg

    Google Scholar 

  49. 49.

    Collins J, Waldmann CM, Drake C, Slavik R, Ha NS, Sergeev M, Lazari M, Shen B, Chin FT, Moore M, Sadeghi S, Phelps ME, Murphy JM, van Dam RM (2017) Production of diverse PET probes with limited resources: 24 18F-labeled compounds prepared with a single radiosynthesizer. Proc Natl Acad Sci USA 114(43):11309–11314

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  50. 50.

    Herman H, Flores G, Quinn K, Eddings M, Olma S, Moore MD, Ding H, Bobinski KP, Wang M, Williams D, Wiliams D, Shen CK, Phelps ME, van Dam RM (2013) Plug-and-play modules for flexible radiosynthesis. Appl Radiat Isot 78:113–124

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  51. 51.

    Taylor MD, Roberts AD, Nickles RJ (1996) Improving the yield of 2-[18F]fluoro-2-deoxyglucose using a microwave cavity. Nucl Med Biol 23:605–609

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  52. 52.

    Kim HW, Jeong JM, Lee YS, Chi DY, Chung KH, Lee DS, Chung JK, Lee MC (2004) Rapid synthesis of [18F]FDG without an evaporation step using an ionic liquid. Appl Radiat Isot 61:1241–1246

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  53. 53.

    Saiki H, Iwata R, Nakanishi H, Wong R, Ishikawa Y, Furumoto S, Yamahara R, Sakamoto K, Ozeki E (2010) Electrochemical concentration of no-carrier-added [18F]fluoride from [18O]water in a disposable microfluidic cell for radiosynthesis of 18F-labeled radiopharmaceuticals. Appl Radiat Isot 68:1703–1708

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    Stewart MN, Hockley BG, Scott PJH (2015) Green approaches to late-stage fluorination: radiosyntheses of 18F-labelled radiopharmaceuticals in ethanol and water. Chem Commun 51:14805–14808

    CAS  Article  Google Scholar 

  55. 55.

    Mathiessen B, Zhuravlev F (2013) Automated solid-phase radiofluorination using polymer-supported phosphazenes. Molecules 18:10531–10547

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. 56.

    Rensch C, Waengler B, Yaroshenko A, Samper V, Baller M, Heumesser N, Ulin J, Riese S, Reischl G (2012) Microfluidic reactor geometries for radiolysis reduction in radiopharmaceuticals. Appl Radiat Isot 70:1691–1697

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  57. 57.

    Vanbrocklin HF (2010) Radiochemistry of positron emission tomography. In: Weissleder R, Ross BD, Rehemtulla A, Gambhir SS (eds) Molecular imaging principles and practice. People’s Medical Publishing House, Raleigh

    Google Scholar 

  58. 58.

    Wang MW, Lin WY, Liu K, Masterman-Smith M, Shen CK (2010) Microfluidics for positron emission tomography (PET) imaging probe development. Mol Imaging 9(4):175–191

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Awasthi V, Watson J, Gali H, Matlock G, McFarland A, Bailey J, Anzellotti A (2014) A “dose on demand” biomarker generator for automated production of [18F]F and [18F]FDG. Appl Radiat Isot 89:167–175

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  60. 60.

    Pascali G, Matesic L (2016) How far are we from dose on demand of short-lived radiopharmaceuticals? In: Kuge Y et al (eds) Perspectives on nuclear medicine for molecular diagnosis and integrated therapy. Springer, Heidelberg. https://doi.org/10.1007/978-4-431-55894-1_6

    Google Scholar 

  61. 61.

    Fludeoxyglucose [18F] injection (2014) 8th ed. Strasbourg: European Directorate for the Quality of the Medicines and Healthcare European Pharmacopoeia, pp 3957–3959

  62. 62.

    Meyer G-J, Matzke KH, Hamacher K, Füchtner F, Steinbach J, Notohamiprodjo G, Zijlstra S (1999) The stability of 2-[18F]fuoro-deoxy-d-glucose towards epimerisation under alkaline conditions. Appl Radiat Isot 51:37–41

    CAS  Article  Google Scholar 

  63. 63.

    Kiselev MY, Tadino V (2006) Stabilization of radiopharmaceuticals labelled with 18-F. US 7,018,614 B2

  64. 64.

    Jacobson MS, Dankwart HR, Mahoney DW (2009) Radiolysis of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) and the role of ethanol and radioactive concentration. Appl Radiat Isot 67:990–995

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  65. 65.

    https://www.criver.com/products-services/qc-microbial-solutions/endotoxin-testing/lal-reagents-accessories/endosafe-cartridge-technology?region=3681. Accessed 21 Mar 2019

  66. 66.

    Huang Y (2018) An overview of PET radiopharmaceuticals in clinical use: regulatory, quality and pharmacopeia monographs of the United States and Europe. https://www.intechopen.com/books/nuclear-medicine-physics/an-overview-of-pet-radiopharmaceuticals-in-clinical-use-regulatory-quality-and-pharmacopeia-monograp. Accessed 19 Mar 2019

  67. 67.

    Koziorowski J (2010) A simple method for the quality control of [18F]FDG. Appl Radiat Isot 68:1740–1742

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  68. 68.

    Nakao R, Ito T, Yamaguchi M, Suzuki K (2008) Simultaneous analysis of FDG, ClDG and Kryptofix 2.2.2. In [18F]FDG preparation by high-performance liquid chromatography with UV detection. Nucl Med Biol 35:239–244

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  69. 69.

    Kilian K, Pękal A, Szkutnik W, Pyrzyńska K (2015) A fast method for the determination of residual solvents in 18FDG and 11C-methionine samples. Microchem J 115:95–99

    Article  CAS  Google Scholar 

  70. 70.

    Anzellotti AI, McFarland AR, Ferguson D, Olson KF (2013) Towards the full automation of QC release tests for [18F]fluoride-based radiotracers. Curr Org Chem 17(19):2153–2158

    CAS  Article  Google Scholar 

  71. 71.

    Ha NS, Sadeghi S, van Dam RM (2017) Recent progress toward microfluidic quality control testing of radiopharmaceuticals. Micromachines 8:337

    PubMed Central  Article  Google Scholar 

  72. 72.

    Tarn MD, Isu A, Archibald SJ, Pamme N (2014) On chip absorbance spectroscopy for the determination of optical clarity and pH for the quality control testing of [18F]FDG radiotracer. In: 18th international conference on miniaturized systems for chemistry and life sciences, San Antonio, Texas, USA, pp 1077–1079

  73. 73.

    Taggart MP, Tarn MD, Esfahani MMN, Schofield D, Brown NJ, Archibald SJ, Deakin T, Pamme N, Thompson LF (2016) Development of radiodetection systems towards miniaturised quality control of PET and SPECT radiopharmaceuticals. Lab Chip 16:1605–1616

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    Archibald S, Pamme N, Brown N, Tarn M (2015) Integrated microfluidic lab-on-a-chip systems for F radiotracer synthesis, purification and quality control. J Nucl Med 56(suppl 3):167

    Google Scholar 

  75. 75.

    Ballinger JR, Koziorowski J (2017) Regulation of PET radiopharmaceuticals production in Europe. In: Khalil MM (ed) Basic science of PET imaging. Springer, Basel, pp 127–143

    Google Scholar 

  76. 76.

    Schwarz SW, Dick D, VanBrocklin HF, Hoffman JM (2014) Regulatory requirements for PET drug production. J Nucl Med 55:1132–1137

    PubMed  Article  PubMed Central  Google Scholar 

  77. 77.

    U.S. Pharmacopeial Convention (1990) USP 22–NF 17, fludeoxyglucose F 18 injection. U.S. Pharmacopeial Convention, Rockville, pp 579–580

    Google Scholar 

  78. 78.

    Meyer G-J, Coenen HH, Waters SL, Langström Cantineau R, StrijCKmans Vaalburg W, Halldin Crouzel C, Mazièr Luxen A (1993) Quality assurance and quality control of short-lived radiopharmaceuticals for PET. In: Stöcklin G, Pike VW (eds) Radiopharmaceuticals for Positron emission tomography—methodological aspects. Springer, Berlin

    Google Scholar 

  79. 79.

    https://www.fda.gov/. Accessed 29 Mar 2019

  80. 80.

    Food and Drug Modernization Act of 1997. U.S. Food and Drug Administration website. http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugand-CosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDAMA/Full-TextofFDAMAlaw/default.htm. Updated 22 Oct 2009. Accessed 3 Apr 2019

  81. 81.

    Sharma S, Baldi A, Singh RK, Sharma RK (2018) Regulatory framework of radiopharmaceuticals: current status and future recommendation. RJLBPCS. https://doi.org/10.26479/2018.0403.25

    Article  Google Scholar 

  82. 82.

    Fludeoxyglucose F 18 injection CMC section. In: Sample Formats: application to manufacture ammonia N 13 injection, fluorodeoxyglucose F 18 injection (FDG F 18), and sodium fluoride F 18 injection—chemistry, manufacturing, and controls section. Food and Drug Administration, Rockville, pp 24–26 (2000). http://www.fda.gov/cder/guidance/cmcsample.pdf. Accessed 3 Apr 2019

  83. 83.

    Hung JC (2002) Comparison of various requirements of the quality assurance procedures for 18F-FDG injection. J Nucl Med 43:1495–1506

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Current good manufacturing practice for positron emission tomography drugs. Fed Regist 2009;74:65409. To be codified at 21 CFR §210, 211, and 212

  85. 85.

    PET drug applications—content and format for NDAs and ANDAs; U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) Aug 2011

  86. 86.

    Council Directive 89/343/EEC of 3 May 1989 extending the scope of Directives 65/65/EEC and 75/319/EEC and laying down additional provisions for radiopharmaceuticals

  87. 87.

    Salvadori PA (2008) Radiopharmaceuticals, drug development and pharmaceutical regulations in Europe. Curr Radiopharm 1:7–11

    CAS  Article  Google Scholar 

  88. 88.

    Meyer G-J, Waters SL, Coenen HH, Luxen A, Maziere B, Langström B (1995) PET radiopharmaceuticals in Europe: current use and data relevant for the formulation of summaries of product characteristics (SPCs). Eur J Nucl Med 22:1420–1432

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  89. 89.

    https://www.ema.europa.eu/en. Accessed 7 Apr 2019

  90. 90.

    https://ec.europa.eu/health/documents/eudralex/vol-4_it. Accessed 7 Apr 2019

  91. 91.

    Decristoforo A, Peñuelas I (2009) Towards a harmonized radiopharmaceutical regulatory framework in Europe? Q J Nucl Med Mol Imaging 53(4):394–401

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals (2007) https://www.eanm.org/publications/guidelines/radiopharmacy/. Accessed 7 Apr 2019

  93. 93.

    Elsinga P, Todde S, Penuelas I, Meyer G, Farstad B, Faivre-Chauvet A, Mikolajczak R, Westera G, Gmeiner-Stopar T, Decristoforo C, The Radiopharmacy Committee of the EANM (2010) Guidance on current good radiopharmacy practice (cGRPP) for the small-scale preparation of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 37:1049–1062

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  94. 94.

    Elsinga PH (2012) Present and future of PET-radiopharmaceuticals. Nucl Med Rev 15(Suppl C):C13–C16

    Google Scholar 

  95. 95.

    Decristoforo C, Patt M (2016) Are we “preparing” radiopharmaceuticals? EJNMMI Radiopharm Chem 1(1):12

    PubMed  PubMed Central  Article  Google Scholar 

  96. 96.

    Poli M, Petroni D, Pardini S, Salvadori PA, Menichetti L (2012) Implementation of a quality assurance system according to GMP and ISO 9001:2008 standard for radiopharmaceutical production in a public research centre. Accredit Qual Assur 17:341–348

    Article  Google Scholar 

  97. 97.

    Minghetti P, Santimaria M, D’Arpino A (2013) Classificazione dei radiofarmaci. In: Lucignani G (ed) Sperimentazione e registrazione dei radiofarmaci. Springer, Milan

    Google Scholar 

  98. 98.

    Wu M, Shu J (2018) Multimodal molecular imaging: current status and future directions. Contrast Media Mol. https://doi.org/10.1155/2018/1382183

    Article  Google Scholar 

  99. 99.

    Ferdová E, Baxa J, Ňaršanská A, Hes O, Fínek J, Topolčan O, Ferda J (2018) Low-dose high-resolution 18F-FDG-PET/CT using time-of-flight and point-spread function reconstructions: a role in the detection of breast carcinoma axillary lymph node metastases. Anticancer Res 38:4145–4148

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  100. 100.

    Yan J, Wu Z, Li S (2017) Extremely low dose 18F-FDG PET imaging and its potential use for lung cancer screening. Transl Cancer Res 6(Suppl 1):S99–S101

    Article  Google Scholar 

  101. 101.

    Fällmar D, Lilja J, Kilander L, Danfors T, Lubberink M, Larsson EM, Sörensen J (2016) Validation of true low-dose 18F-FDG PET of the brain. Am J Nucl Med Mol Imaging 6(5):269–276

    PubMed  PubMed Central  Google Scholar 

  102. 102.

    Karakatsanis NA, Lodge MA, Tahari AK, Zhou Y, Wahl RA, Rahmim A (2013) Dynamic whole body PET parametric imaging: I. Concept, acquisition protocol optimization and clinical application. Phys Med Biol 58(20):7391–7418

    PubMed  PubMed Central  Article  Google Scholar 

  103. 103.

    Nguyen NC, Vercher-Conejero JL, Sattar A, Miller MA, Maniawski PJ, Jordan DW, Muzic RF Jr, Su K, O’Donnell JK, Faulhaber PF (2015) Image quality and diagnostic performance of a digital pet prototype in patients with oncologic diseases: initial experience and comparison with analog PET. J Nucl Med 56(9):1378–1385

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  104. 104.

    Wojtylak P, Avril N, ODonnell J, Faulhaber P (2014) Initial clinical experience in digital PET/CT. J Nucl Med 55(suppl 1):2503

    Google Scholar 

  105. 105.

    Vandenberghe S, Mikhaylova E, D’Hoe E, Mollet P, Karp JS (2016) Recent developments in time-of-flight PET. EJNMMI Phys 3:3

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  106. 106.

    Knopp M, Wright C, Binzel K, Friel M, Moore R, Mohamed M, Giesel F, Zhang J, Maniawski P, Knopp M (2018) Ultra-fast wholebody PET/CT: a phase II intra-individual comparison trial to standard acquisition performed using digital PET/CT. J Nucl Med 59(Suppl 1):450

    Google Scholar 

  107. 107.

    http://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=hlth_rs_equip&lang=en. Accessed 2 May 2019

  108. 108.

    https://www.england.nhs.uk/statistics/statistical-work-areas/diagnostic-imaging-dataset/. Accessed 2 May 2019

Download references

Author information



Corresponding author

Correspondence to D. Petroni.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Petroni, D., Menichetti, L. & Poli, M. Historical and radiopharmaceutical relevance of [18F]FDG. J Radioanal Nucl Chem 323, 1017–1031 (2020). https://doi.org/10.1007/s10967-020-07013-y

Download citation


  • [18F]FDG
  • PET
  • Automated synthesizer
  • Quality control
  • Legislation