PET Radiochemistry and Radiopharmacy

  • Mark S. JacobsonEmail author
  • Raymond A. Steichen
  • Patrick J. Peller
Part of the Medical Radiology book series (MEDRAD)


The vast majority of PET radiopharmaceuticals today are cyclotron produced. Carbon-11 (11C), Nitrogen-13 (13N), Oxygen-15 (15O) products are created for in-house use only due to their short half-lives. The longer half-life of Fluorine-18 means that 18F-labeled PET radiotracers can be widely distributed. Production of radiopharmaceuticals is computer-controlled and automated. Automation increases both reliability and efficiency of PET operations while decreasing the radiation dose to the staff. For today, FDG remains the workhorse of oncologic PET imaging. Additional 18F PET radiotracers directed at a range of molecular processes are being studied and should become available in the future.


Positron Emission Tomography Positron Emission Tomography Imaging Positron Emission Tomography Tracer Choline Kinase Oncologic Imaging 
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.


  1. Ak I, Stokkel MP, Pauwels EK (2000) Positron emission tomography with 2-[18F]fluoro-2-deoxy-d-glucose in oncology. Part II. The clinical value in detecting and staging primary tumors. J Cancer Res Clin Oncol 126:560–574PubMedCrossRefGoogle Scholar
  2. Avril N, Menzel M, Dose J, Schelling M, Weber W, Jänicke F, Nathrath W, Schwaiger M (2001) Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis. J Nucl Med 42(1):9–16PubMedGoogle Scholar
  3. Bading JR, Shields AF (2008) Imaging of cell proliferation: status and prospects. J Nucl Med 49(2):648-805Google Scholar
  4. Becherer A, Szabo M, Karanikas G et al (2004) Imaging of advanced neuroendocrine tumors with [18]F-FDOPA PET. J Nucl Med 45:1161–1167PubMedGoogle Scholar
  5. Beck R, Roper B, Carlsen JM et al (2007) Pretreatment 18F-FAZA PET predicts success of hypoxia-directed radiochemotherapy using tirapazamine. J Nucl Med 48:973–980PubMedCrossRefGoogle Scholar
  6. Blake GM, Park-Holohan SJ, Cook GJ et al (2001) Quantitative studies of bone with the use of 18F-fluoride and 99mTc-methylene diphosphonate. Semin Nucl Med 31:28–49PubMedCrossRefGoogle Scholar
  7. Blau M, Nagler W, Bender MA (1962) A new isotope for bone scanning. J Nucl Med 3:332–334PubMedGoogle Scholar
  8. Bos R, van Der Hoeven JJ, van Der Wall E, van Der Groep P, van Diest PJ, Comans EF, Joshi U, Semenza GL, Hoekstra OS, Lammertsma AA, Molthoff CF (2002) Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol 20(2):379–387PubMedCrossRefGoogle Scholar
  9. Breeman WAP, Verbruggen AM (2007) The 68 Ge/68 Ga generator has high potential, but when can we use 68 Ga-labeled tracers in clinical routine? Eur J Nucl Med Mol Imaging 34:978–981PubMedCrossRefGoogle Scholar
  10. Buck AK, Halter G, Schirrmeister H et al (2003) Imaging of proliferation in lung tumors with PET: 18FLT versus 18FDG. J Nucl Med 44:1426–1431PubMedGoogle Scholar
  11. Carolan P, Hunt C, McConnell D et al (2012) Radiation exposure reduction to PET technologists with the use of an automated dosage delivery system. J Nucl Med 53:2185Google Scholar
  12. Ceyssens S, Van Laere K, de Groot T et al (2006) [11C]methionine PET, histopathology, and survival in primary brain tumors and recurrence. AJNR 27:1432–1437PubMedGoogle Scholar
  13. Chen W, Cloughesy T, Kamdar N et al (2005) Imaging proliferation in brain tumors with 18-FLT PET: comparison with 18F-FDG. J Nucl Med 46:945–952PubMedGoogle Scholar
  14. Cobben DC, Elsinga PH, Suurmeijer AJ et al (2004) Detection and grading of soft tissue sarcomas of the extremities with 18F–3-fluoro-3-deoxy-l-thymidine. Clin Cancer Res 10:1685–1690PubMedCrossRefGoogle Scholar
  15. Cobben DC, Jager PL, Elsinga PH et al (2003) 18F–3-fluoro-3-deoxy-l-thymidine: a new tracer or staging of metastatic melanoma? J Nucl Med 44:1927–1932PubMedGoogle Scholar
  16. Coleman RE (1999) PET in lung cancer. J Nucl Med 40(5):814–820PubMedGoogle Scholar
  17. DeGrado TR, Coleman RE, Wang S et al (2001) Synthesis and evaluation of 18F labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. Cancer Res 61:110–117PubMedGoogle Scholar
  18. Delbeke D (1999) Oncological applications of FDG PET imaging. J Nucl Med 40(10):1706–1715PubMedGoogle Scholar
  19. Even-Sapir E, Metser U, Flusser G et al (2004) Assessment of malignant skeletal disease: initial experience with 18F–fluoride PET/CT and comparison between 18F–fluoride PET and 18F–fluoride PET/CT. J Nucl Med 45:272–278PubMedGoogle Scholar
  20. Even-Sapir E, Metser U, Mishani E et al (2006) The detection of bone metastases in patient with high-risk prostate cancer: 99mTc-MDP planar bone scintigraphy, single- and -field-of view SPECT, 18F–fluoride PET, and 18F–fluoride PET/CT. J Nucl Med 47:287–297PubMedGoogle Scholar
  21. Even-Sapir E (2005) Imaging of malignant bone involvement by morphologic, scintigraphic, and hybrid modalities. J Nucl Med 46:1356–1367PubMedGoogle Scholar
  22. Foo SS, Abbott DF, Lawrentschuk N et al (2004) Functional imaging of intra-tumoral hypoxia. Mol Imaging Biol 6:291–305PubMedCrossRefGoogle Scholar
  23. Francis DL, Visvikis D, Costa DC et al (2003) Potential impact of [18F]-3-fluoro-3-deoxy-thymidine versus [18F]-fluoro-2- deoxy-d-glucose in positron emission tomography for colorectal cancer. Eur J Nucl Med Mol Imaging 30:988–994PubMedCrossRefGoogle Scholar
  24. Galldiks N, Kracht LW, Burghaus L et al (2006) Use of 11Cmethionine PET to monitor the effects of temozolomide chemotherapy in malignant gliomas. Eur J Nucl Med Mol Imaging 33:516–524PubMedCrossRefGoogle Scholar
  25. Gatley SJ (2003) Labeled glucose analogs in the genomic era. J Nucl Med 44(7):1082–1086PubMedGoogle Scholar
  26. Hara T, Kosaka N, Kishi H (2002) Development of [18F]-Fluoroethylcholine for cancer imaging with PET: synthesis, biochemistry, and prostate cancer imaging. J Nucl Med 43:187–199PubMedGoogle Scholar
  27. Hara T, Kosaka N, Shinoura N et al (1997) PET imaging of brain tumor with [methyl-11C] choline. J Nucl Med 38:842–847PubMedGoogle Scholar
  28. Hetzel M, Arslandemir C, Konig HH et al (2003) F-18 NaF PET for detection of bone metastases in lung cancer: accuracy, cost-effectiveness and impact on patient management. J Bone Miner Res 18:2206–2214PubMedCrossRefGoogle Scholar
  29. Hicks RJ, Rischin D, Fisher R et al (2005) Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent. Eur J Nucl Med Mol Imaging 32:1384–1391PubMedCrossRefGoogle Scholar
  30. Higashi T, Saga T, Nakamoto Y, Ishimori T, Mamede MH, Wada M, Doi R, Hosotani R, Imamura M, Konishi J (2002) Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer. J Nucl Med 43(2):173–180Google Scholar
  31. Hoegerle S, Altehoefer C, Ghanem N et al (2001a) 18F-DOPA positron emission tomography for tumor detection in patients with medullary thyroid carcinoma and elevated calcitonin levels. Eur J Nucl Med 28:64–71PubMedCrossRefGoogle Scholar
  32. Hoegerle S, Altehoefer C, Ghanem N, Koehler G, Waller CF, Scheruebl H, Moser E, Nitzsche E (2001b) Whole-body 18F dopa PET for detection of gastrointestinal carcinoid tumors. Radiology 220(2):373–380PubMedGoogle Scholar
  33. Hoegerle S, Nitzsche E, Altehoefer C et al (2002) Pheochromocytomas: detection with 18F DOPA whole body PET—initial results. Radiology 222:507–512PubMedCrossRefGoogle Scholar
  34. Hoegerle S, Schneider B, Kraft A, Moser E, Nitzsche EU (1999) Imaging of a metastatic gastrointestinal carcinoid by F-18-DOPA positron emission tomography. Nuklearmedizin 38:127–130PubMedGoogle Scholar
  35. Howard BV, Howard WJ (1975) Lipids in normal and tumor cells in culture. Prog Biochem Pharmacol 10:135–166PubMedGoogle Scholar
  36. Ido T, Wan CN, Casella JS et al (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 Radiopharmacol 14:175–183CrossRefGoogle Scholar
  37. Ilias I, Chen CC, Carrasquillo JA et al (2008) Comparison of 6-[18F]-fluorodopamine positron emission tomography to [123I]-metaiodobenzylguanidine and [111In]-pentetreotide scintigraphy in the localization of non-metastatic and metastatic pheochromocytoma. J Nucl Med 49:1613–1619PubMedCrossRefGoogle Scholar
  38. Jackowski S (1994) Coordination of membrane phospholipid synthesis with the cell cycle. J Biol Chem 269:3858–3867PubMedGoogle Scholar
  39. Jacobs AH, Thomas A, Kracht LW et al (2005) 18F-fluoro-l-thymidine and 11C-Methylmetionine as markers of increased transport and proliferation in brain tumors. J Nucl Med 46:1948–1958PubMedGoogle Scholar
  40. Kaschten B, Stevenaert A, Sadzot B et al (1998) Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J Nucl Med 39:778–785PubMedGoogle Scholar
  41. Koh WJ, Bergman KS, Rasey JS et al (1995) Evaluation of oxygenation status during fractionated radiotherapy in human non-small cell lung cancers using [F-18]fluoromisonidazole positron emission tomography. Int J Radiat Oncol Biol Phys 33:391–398PubMedCrossRefGoogle Scholar
  42. Laszlo J, Humphreys SR, Goldin A (1960) Effects of glucose analogues (2-deoxy-d-glucose, 2-deoxy-D-galactose) on experimental tumors. J Natl Cancer Inst 24:267–281PubMedGoogle Scholar
  43. Lee ST, Scott AM (2007) Hypoxia positron emission tomography imaging with 18F-fluoromisonidazole. Semin Nucl Med 37:451–461PubMedCrossRefGoogle Scholar
  44. Luxen A, Guillaume M, Melega WP et al (1992) Production of 6-[18F]fluoro-L-dopa and its metabolism in vivo—a critical review. Int J Radiat Appl Instrum B 19:149–158Google Scholar
  45. McCarthy TJ, Welch MJ (1998) The state of positron emitting radionuclide production in 1997. Semin Nucl Med 28(3):235–46Google Scholar
  46. Mees G, Dierckx R, Vangestel C et al (2009) Molecular imaging of hypoxia with radiolabeled agents. Eur J Nucl Med Mol Imaging 36:1674–1686PubMedCrossRefGoogle Scholar
  47. Mertens K, Slaets D, Lambert B, Acou M, De Vos F, Goethals I (2010) PET with (18)F-labeled choline-based tracers for tumor imaging: a review of the literature. Eur J Nucl Med Mol Imaging 37(11):2188–2193Google Scholar
  48. Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, Hosokawa M, Kohanawa M, Tamaki N (2001) FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. J Nucl Med 42(10):1551–1555PubMedGoogle Scholar
  49. Nutt R (2002) The history of positron emission tomography (PET). Mol Imaging Biol 4:11–26PubMedCrossRefGoogle Scholar
  50. Nuutinen J, Sonninen P, Lehikoinen P et al (2000) Radiotherapy treatment planning and long-term follow-up with [(11)C] methionine PET in patients with low-grade astrocytoma. Int J Radiat Oncol Biol Phys 48:43–52PubMedCrossRefGoogle Scholar
  51. Pacák J, Cerny M (2002) History of the First Synthesis of 2-Deoxy-2-Fluoro-d-Glucose the Unlabeled Forerunner of 2-Deoxy-2-[18F]Fluoro-d-Glucose. Mol Imaging Biol 4:353–354Google Scholar
  52. Picchio M, Messa C, Landoni C et al (2003) Value of [11C]choline positron emission tomography for re-staging prostate cancer: a comparison with [18F] fluorodeoxyglucose-positron emission tomography. J Urol 169:1337–1340PubMedCrossRefGoogle Scholar
  53. Rajendran JG, Schwartz DL, O’Sullivan J et al (2006) Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res 12:5435–5441PubMedCrossRefGoogle Scholar
  54. Rasey JS, Grunbaum Z, Magee S et al (1987) Characterization of radiolabeled fluoromisonidazole as a probe for hypoxic cells. Radiat Res 111:292–304PubMedCrossRefGoogle Scholar
  55. Ribom D, Engler H, Blomquist E, Smits A (2002) Potential significance of (11)C-methionine PET as marker for the radiosensitivity of low-grade gliomas. Eur J Nucl Med Mol Imaging 29:632–640PubMedCrossRefGoogle Scholar
  56. Rice SL, Roney CA, Daumar P, Lewis JS (2011) The next generation of positron emission tomography radiopharmaceuticals in oncology. Semin Nucl Med 41(4):265–282Google Scholar
  57. Roivainen A, Forsback S, Grönroos T et al (2000) Blood metabolism of [methyl-11C]choline; implications for in vivo imaging with positron emission tomography. Eur J Nucl Med 27:25–32PubMedCrossRefGoogle Scholar
  58. Rufini V, Calcagni ML, Baum RP (2007) Imaging of neuroendocrine tumors. Semin Nucl Med 36:228–247Google Scholar
  59. Schiepers C, Nuytes J, Bormans G et al (1997) Fluoride kinetics of the axial skeleton measured in vivo with fluorine-18-fluoride PET. J Nucl Med 38:1970–1976PubMedGoogle Scholar
  60. Schirrmeister H, Glatting G, Hetzel J et al (2001) Prospective evaluation of clinical value of planar bone scans, SPECT, and18F-labeled NaF PET in newly diagnosed lung cancer. J Nucl Med 42:1800–1804PubMedGoogle Scholar
  61. Schlyer DJ (2004) PET tracers and radiochemistry. Ann Acad Med Singapore 33:146–154PubMedGoogle Scholar
  62. Schuster DM, John R, Votaw JR et al (2007) Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. J Nucl Med 48:56–63PubMedGoogle Scholar
  63. Shaiju VS, Sharma SD, Kumar R, Sarin B (2009) Target foil rupture scenario and provision for handling different models of medical cyclotrons used in India. J Med Phys 34(3):161–166PubMedCrossRefGoogle Scholar
  64. Sharma S, Krause G, Ebadi M (2006) Radiation safety and quality control in the cyclotron laboratory. Radiat Prot Dosimetry 118:431–439PubMedCrossRefGoogle Scholar
  65. Sherley JL, Kelly TJ (1988) Regulation of human thymidine kinase during the cell cycle. J Biol Chem 263:8350–8358PubMedGoogle Scholar
  66. Shields AF (2003) PET imaging with 18F-FLT and thymidine analogs: promise and pitfalls. J Nucl Med 44:1432–1434PubMedGoogle Scholar
  67. Shields AF, Grierson JR, Kozawa SM et al (1996) Development of labeled thymidine analogs for imaging tumor proliferation. Nucl Med Biol 23:17–22PubMedCrossRefGoogle Scholar
  68. Shields AF, Grierson JR, Dohmen BM et al (1998) Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 4:1334–1336PubMedCrossRefGoogle Scholar
  69. Smith TA (2000) Mammalian hexokinases and their abnormal expression in cancer. Br J Biomed Sci 57:170–178PubMedGoogle Scholar
  70. Smyczek-Gargya B, Fersis N, Dittmann H et al (2004) PET with [18F]fluorothymidine for imaging of primary breast cancer: a pilot study. Eur J Nucl Med Mol Imaging 31:720–724PubMedCrossRefGoogle Scholar
  71. Vallabhajosula S, Solnes L, Vallabhajosula B (2011) A broad overview of positron emission tomography radiopharmaceuticals and clinical applications: what is new? Semin Nucl Med 41(4):246–264Google Scholar
  72. Vallabhajosula S (2007) (18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization. Semin Nucl Med 37(6):400–419PubMedCrossRefGoogle Scholar
  73. Vaupel P, Schlenger K, Hoeckel M (1992) Blood flow and tissue oxygenation of human tumors: an update. Adv Exp Med Biol 317:139–151PubMedCrossRefGoogle Scholar
  74. Vesselle H, Grierson J, Muzi M et al (2002) In vivo validation of 3′deoxy-3′-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors. Clin Cancer Res 8:3315–3323PubMedGoogle Scholar
  75. Warburg O (1956) On the origin of cancer cells. Science 123:309–314PubMedCrossRefGoogle Scholar
  76. Williams HA, Robinson S, Julyan P et al (2005) A comparison of PET imaging characteristics of various copper radioisotopes. Eur J Nucl Med Mol Imaging 32:1473–1480PubMedCrossRefGoogle Scholar
  77. Zhao S, Kuge Y, Tsukamoto E, Mochizuki T, Kato T, Hikosaka K, Hosokawa M, Kohanawa M, Tamaki N (2001) Effects of insulin and glucose loading on FDG uptake in experimental malignant tumors and inflammatory lesions. Eur J Nucl Med 28(6):730–735PubMedCrossRefGoogle Scholar
  78. Zhernosekov KP, Filosofov DV, Baum RP et al (2007) Processing of generator-produced 68 Ga for medical application. J Nucl Med 48:1741–1748PubMedCrossRefGoogle Scholar
  79. Zweit J, Goodall R, Cox M, Babich JW, Potter GA, Sharma HL, Ott RJ (1992) Development of a high performance zinc-62/copper-62 radionuclide generator for positron emission tomography. Eur J Nucl Med 19(6):418–425PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Mark S. Jacobson
    • 1
    Email author
  • Raymond A. Steichen
    • 2
  • Patrick J. Peller
    • 1
  1. 1.Department of RadiologyMayo ClinicRochesterUSA
  2. 2.Section of Equipment ServicesMayo ClinicRochesterUSA

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