Skip to main content
SpringerLink
Log in

Non-peptidyl 18F-Labelled PET Tracers as Radioindicators for the Noninvasive Detection of Cancer

  • Chapter
  • First Online:
Molecular Imaging in Oncology

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 187))

Abstract

Noninvasive molecular imaging of cancer by means of the state-of-the-art scintigraphic imaging modalities PET and PET/CT represents a powerful diagnostic approach in modern nuclear medicine. Radiotracers labelled with the prominent positron emitter 18F can be defined as molecular PET imaging probes targeting discrete biological structures dysregulated in the progression of cancer and, thus, are capable to detect oncological pathologies in vivo at the cellular and subcellular level in a timely manner. The use of such radioindicators, also called radiotracers, allows the detection of their path and fate in the living organism. In the course of tumourigenesis, several molecular processes become dysregulated and radiotracers are available to image these abnormal characteristics. This chapter describes 18F-labelled radiopharmaceuticals that are frequently used in oncological PET and PET/CT. In particular, non-peptidyl radiotracers for the imaging of glucose utilisation, amino acid transport and protein synthesis, membrane lipid synthesis, cell proliferation, hypoxia, oestrogen receptor status and bone mineralisation of tumours are introduced. The compounds are described regarding their radiochemical synthesis approaches and their in vivo metabolism and accumulation mechanisms. Furthermore, concrete clinical perspectives are given, that refer to highly potent and promising oncological radiotracers which are currently in preclinical development.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alauddin MM, Conti PS, Fissekis JD (2002) Synthesis of [18F]-labeled 2′-deoxy-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([18F]-FMAU). J Label Compd Radiopharm 45:583–590

    CAS  Google Scholar 

  • Asti M, Farioli D, Iori M, Guidotti C, Versari A, Salvo D (2010) Efficient automated one-step synthesis of 2-[18F]fluoroethylcholine for clinical imaging: optimized reaction conditions and improved quality controls of different synthetic approaches. Nucl Med Biol 37:209–315

    Google Scholar 

  • Bading JR, Shields AF (2008) Imaging of cell proliferation: status and prospects. J Nucl Med 49:64S–80S

    PubMed  CAS  Google Scholar 

  • Bauman G, Belhocine T, Kovacs M, Ward A, Beheshti M, Rachinsky I (2012) 18F-fluorocholine for prostate cancer imaging: a systematic review of the literature. Prostate Cancer Prostatic Dis 15:45–55

    PubMed  CAS  Google Scholar 

  • Beheshti M, Pöcher S, Vali R, Waldenberger P, Broinger G, Nader M, Kohlfürst S, Pirich C, Dralle H, Langsteger W (2009) The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PET-CT. Eur Radiol 19:1425–1434

    PubMed  Google Scholar 

  • Been LB, Suurmeijer AJ, Cobben DC, Jager PL, Hoekstra HJ, Elsinga PH (2004) [18F]FLT-PET in oncology: current status and opportunities. Eur J Nucl Med Mol Imaging 31:1659–1672

    PubMed  Google Scholar 

  • Beheshti M, Vali R, Waldenberger P, Fitz F, Nader M, Loidl W, Broinger G, Stoiber F, Foglman I, Langsteger W (2008) Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET-CT: a comparative study. Eur J Nucl Med Mol Imaging 35:1766–1774

    PubMed  Google Scholar 

  • Belt JA, Marina NM, Phelps DA, Crawford CR (1993) Nucleoside transport in normal and neoplastic cells. Adv Enzyme Regul 33:235–252

    PubMed  CAS  Google Scholar 

  • Berg JM, Tymoczko JL, Stryer L (2006) Biochemistry, 6th edn. W.H. Freeman & Company, New York

    Google Scholar 

  • Bettio A, Honer M, Müller C, Brühlmeier M, Müller U, Schibli R, Groehn V, Schubiger AP, Ametamey SM (2006) Synthesis and preclinical evaluation of a folic acid derivative labeled with 18F for PET imaging of folate receptor-positive tumors. J Nucl Med 47:1153–1160

    PubMed  CAS  Google Scholar 

  • Blau M, Nagler W, Bender MA (1962) Fluorine-18: a new isotope for bone scanning. J Nucl Med 3:332–334

    PubMed  CAS  Google Scholar 

  • Bouchelouche K, Oehr P (2008) Positron emission tomography and positron emission tomography/computerized tomography of urological malignancies: an update review. J Urol 179:34–45

    PubMed  CAS  Google Scholar 

  • Brock CS, Meikle SR, Price P (1997) Does fluorine-18 fluorodeoxyglucose metabolic imaging of tumors benefit oncology? Eur J Nucl Med 24:691–705

    PubMed  CAS  Google Scholar 

  • Busch H, Davis JR, Honig GR, Anderson DC, Nair PV, Nyhan WL (1959) The uptake of a variety of amino acids into nuclear proteins of tumors and other tissues. Cancer Res 19:1030–1039

    PubMed  CAS  Google Scholar 

  • Chapman JD, Franko AJ, Sharplin J (1981) A marker for hypoxic cells in tumours with potential clinical applicability. Br J Cancer 43:546–550

    PubMed  CAS  Google Scholar 

  • Cherif A, Yang DJ, Tansey W, Kim EE, Wallace S (1994) Rapid synthesis of 3-[18F]fluoro-1-(2′-nitro-1′-imidazolyl)-2-propanol ([18F]fluoromisonidazole). Pharm Res 11:466–469

    PubMed  CAS  Google Scholar 

  • Christensen HN (1990) Role of amino acid transport and countertransport in nutrition and metabolism. Phys Rev 70:43–77

    CAS  Google Scholar 

  • Clary GL, Tsai CF, Guynn RW (1987) Substrate specificity of choline kinase. Arch Biochem Biophys 254:214–221

    PubMed  CAS  Google Scholar 

  • Cleaver JE (1967) Thymidine metabolism and cell kinetics. Front Biol 6:43–100

    Google Scholar 

  • Coleman R, DeGrado T, Wang S, Baldwin S, Orr M, Reiman R, Price D (2000) Preliminary evaluation of F-18 fluorocholine (FCH) as a PET tumor imaging agent. Clin Positron Imaging 3:147

    PubMed  Google Scholar 

  • DeGrado TR, Baldwin SW, Wang S, Orr MD, Liao RP, Friedman HS, Reiman R, Price DT, Coleman RE (2001) Synthesis and evaluation of 18F-labeled choline analogs as oncologic PET tracers. J Nucl Med 42:1805–1814

    PubMed  CAS  Google Scholar 

  • DeGrado TR, Coleman RE, Wang S, Baldwin SW, Orr MD, Robertson CN, Polascik TJ, Price DT (2000) Synthesis and evaluation of 18F-labeled choline as an oncologic tracer for positron emission tomography: initial findings in prostate cancer. Cancer Res 61:110–117

    Google Scholar 

  • Deves R, Krupka RM (1979) The binding and translocation steps in transport as related to substrate structure: a study of the choline carrier of erythrocytes. Biochim Biophys Acta 557:469–485

    PubMed  CAS  Google Scholar 

  • Dollé F, Demphel S, Hinnen F, Fournier D, Vaufrey F, Crouzel C (1998) 6-[18F]Fluoro-L-DOPA by radiofluorodestannylation: a short and simple synthesis of a new labelling precursor. J Label Compd Radiopharm 41:105–114

    Google Scholar 

  • Dunet V, Rossier C, Buck A, Stupp R, Prior JO (2012) Performance of 18F-Fluoro-Ethyl-Tyrosine (18F-FET) PET for the differential diagnosis of primary brain tumor: a systematic review and metaanalysis. J Nucl Med 53:207–214

    PubMed  CAS  Google Scholar 

  • Eckel F, Herrmann K, Schmidt S, Hillerer C, Wieder HA, Krause BJ, Schuster T, Langer R, Wester HJ, Schmid RM, Schwaiger M, Buck AK (2009) Imaging of proliferation in hepatocellular carcinoma with the in vivo marker 18F-fluorothymidine. J Nucl Med 50:1441–1447

    PubMed  CAS  Google Scholar 

  • Even-Sapir E, Metser U, Mishani E, Lievshitz G, Lerman H, Leibovitch I (2006) The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-Fluoride PET, and 18F-fluoride PET/CT. J Nucl Med 47:287–297

    PubMed  Google Scholar 

  • Faust A, Hermann S, Wagner S, Haufe G, Schober O, Schäfers M, Kopka K (2009) Molecular imaging of apoptosis in vivo with scintigraphic and optical biomarkers—a status report. Anticancer Agents Med Chem 9:968–985

    PubMed  CAS  Google Scholar 

  • Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, Dimitrov NV, Wolmark N, Wickerham DL, Fisher ER, Margolese R, Robidoux A, Shibata H, Terz J, Paterson AHJ, Feldman MI, Farrar W, Evans J, Lickley HL, Ketner M (1989) A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 320:479–484

    PubMed  CAS  Google Scholar 

  • Foo SS, Abbott DF, Lawrentschuk N, Scott AM (2004) Functional imaging of intratumoral hypoxia. Mol Imaging Biol 6:291–305

    PubMed  Google Scholar 

  • Füchtner F, Steinbach J, Mäding 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

    Google Scholar 

  • Füchtner F, Zessin J, Mäding P, Wüst F (2008) Aspects of 6-[18F]fluoro-l-DOPA preparation. Deuterochloroform as a substitute solvent for Freon 11. Nuklearmedizin 47:62–64

    PubMed  Google Scholar 

  • Garnett ES, Firnau G, Chan PK, Sood S, Belbeck LW (1978) [18F]fluoro-dopa, an analogue of dopa, and its use in direct external measurements of storage, degradation, and turnover of intracerebral dopamine. Proc Natl Acad Sci U S A 75:464–467

    PubMed  CAS  Google Scholar 

  • Garnett ES, Firnau G, Nahmias C (1983) Dopamine visualized in the basal ganglia of living man. Nature 305:137–138

    PubMed  CAS  Google Scholar 

  • Gallagher BM, Fowler JS, Gutterson NI, McGregor RR, Wan CN, Wolf AP (1978) Metabolic trapping as a principle of radiopharmaceutical design: some factors responsible for the biodistribution of [18F]-2-deoxy-2-fluoro-d-glucose. J Nucl Med 19:1154–1161

    PubMed  CAS  Google Scholar 

  • Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC (1953) The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol 26:638–648

    PubMed  CAS  Google Scholar 

  • Grierson JR, Link JM, Mathis CA, Rasey JS, Krohn KA (1989) A radiosynthesis of fluorine-18 fluoromisonidazole. J Nucl Med 30:343–350

    PubMed  CAS  Google Scholar 

  • Grosu AL, Souvatzoglou M, Röper B, Dobritz M, Wiedenmann N, Jacob V, Wester HJ, Reischl G, Machulla HJ, Schwaiger M, Molls M, Piert M (2007) Hypoxia imaging with FAZA-PET and theoretical considerations with regard to dose painting for individualization of radiotherapy in patients with head and neck cancer. Int J Radiat Oncol Biol Phys 69:541–551

    PubMed  CAS  Google Scholar 

  • Haerle SK, Fischer DR, Schmid DT, Ahmad N, Huber GF, Buck A (2011) 18F-FET PET/CT in advanced head and neck squamous cell carcinoma: an intra-individual comparison with 18F-FDG PET/CT. Mol Imaging Biol 13:1036–1042

    PubMed  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

    PubMed  CAS  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 

  • Hannanah D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Google Scholar 

  • 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 43:187–199

    PubMed  CAS  Google Scholar 

  • Hawkins RA, Choi Y, Huang SC, Hoh CK, Dahlbom M, Schiepers C, Satyamurthy N, Barrio JR, Phelps ME (1992) Evaluation of the skeletal kinetics of fluorine-18-fluoride ion with PET. J Nucl Med 33:633–642

    PubMed  CAS  Google Scholar 

  • Hayashi K, Furutsuka K, Takei M, Muto M, Nakao R, Aki H, Suzuki K, Fukumura T (2011) High-yield automated synthesis of [18F]fluoroazomycin arabinoside ([18F]FAZA) for hypoxia-specific tumor imaging. Appl Radiat Isot 69:1007–1013

    PubMed  CAS  Google Scholar 

  • Heiss P, Mayer S, Herz M, Wester HJ, Schwaiger M, Senekowitsch-Schmidtke R (1999) Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-l-tyrosine in vitro and in vivo. J Nucl Med 40:1367–1373

    PubMed  CAS  Google Scholar 

  • Hengstschläger M, Knöfler M, Müllner EW, Ogris E, Wintersberger E, Wawra E (1994) Different regulation of thymidine kinase during the cell cycle of normal versus DNA tumor virus-transformed cells. J Biol Chem 269:13836–13842

    PubMed  Google Scholar 

  • Hoegerle S, Altehoefer C, Ghanem N, Brink I, Moser E, Nitzsche E (2001) 18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels. Eur J Nucl Med 28:64–71

    PubMed  CAS  Google Scholar 

  • Hoegerle S, Nitzsche E, Altehoefer C, Ghanem N, Manz T, Brink I, Reincke M, Moser E, Neumann HP (2002) Pheochromocytomas: detection with 18F DOPA whole body PET–initial results. Radiology 222:507–512

    PubMed  Google Scholar 

  • Höltke C, Faust A, Breyholz HJ, Kopka K, Schober O, Riemann B, Bremer C, Schäfers M, Wagner S (2009) Non-invasive approaches to visualize the endothelin axis in vivo using state-of-the-art molecular imaging modalities. Mini Rev Med Chem 9:1580–1595

    PubMed  Google Scholar 

  • Imani F, Agopian VG, Auerbach MS, Walter MA, Imani F, Benz MR, Dumont RA, Lai CK, Czernin JG, Yeh MW (2009) 18F-FDOPA PET and PET/CT accurately localize pheochromocytomas. J Nucl Med 50:513–519

    PubMed  Google Scholar 

  • Isselbacher KJ (1972) Sugar and amino acid transport by cells in culture: differences between normal and malignant cells. N Engl J Med 286:929–933

    PubMed  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

    PubMed  CAS  Google Scholar 

  • Jager PL, Chirakal R, Marriott CJ, Brouwers AH, Koopmans KP, Gulenchyn KY (2008) 6-L-18F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors: basic aspects and emerging clinical applications. J Nucl Med 49:573–586

    PubMed  CAS  Google Scholar 

  • Johnstone RM, Scholefield PG (1965) Amino acid transport in tumor cells. Adv Cancer Res 9:143–226

    PubMed  CAS  Google Scholar 

  • Kameyama R, Yamamoto Y, Izuishi K, Sano T, Nishiyama Y (2011) Correlation of 18F-FLT uptake with equilibrative nucleoside transporter-1 and thymidine kinase-1 expressions in gastrointestinal cancer. Nucl Med Commun 32:460–465

    PubMed  CAS  Google Scholar 

  • Kameyama R, Yamamoto Y, Izuishi K, Takebayashi R, Hagiike M, Murota M, Kaji M, Haba R, Nishiyama Y (2009) Detection of gastric cancer using 18F-FLT PET: comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging 36:382–388

    PubMed  Google Scholar 

  • Kämäräinen EL, Kyllönen T, Nihtilä O, Björk H, Solin O (2004) Preparation of fluorine-18-labelled fluoromisonidazole using two different synthesis methods. J Label Compd Radiopharm 47:37–45

    Google Scholar 

  • Kao CH, Hsu WL, Xie HL, Lin MC, Lan WC, Chao HY (2011) GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP Fluorodopa F 18 Injection. Ann Nucl Med 25: 309-316

    Google Scholar 

  • Kauhanen S, Schalin-Jäntti C, Seppänen M, Kajander S, Virtanen S, Schildt J, Lisinen I, Ahonen A, Heiskanen I, Väisänen M, Arola J, Korsoff P, Ebeling T, Sane T, Minn H, Välimäki MJ, Nuutila P (2011) Complementary roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in medullary thyroid cancer. J Nucl Med 52:1855–1863

    PubMed  CAS  Google Scholar 

  • Kauhanen S, Seppänen M, Ovaska J, Minn H, Bergman J, Korsoff P, Salmela P, Saltevo J, Sane T, Välimäki M, Nuutila P (2009) The clinical value of [18F]fluoro-dihydroxyphenylalanine positron emission tomography in primary diagnosis, staging, and restaging of neuroendocrine tumors. Endocr Relat Cancer 16:255–265

    PubMed  CAS  Google Scholar 

  • Kawaguchi M, Tateishi U, Shizukuishi K, Suzuki A, Inoue T (2010) 18F-fluoride uptake in bone metastasis: morphologic and metabolic analysis on integrated PET/CT. Ann Nucl Med 24:241–247

    PubMed  Google Scholar 

  • Kawai N, Maeda Y, Kudomi N, Miyake K, Okada M, Yamamoto Y, Nishiyama Y, Tamiya T (2011) Correlation of biological aggressiveness assessed by 11C-methionine PET and hypoxic burden assessed by 18F-fluoromisonidazole PET in newly diagnosed glioblastoma. Eur J Nucl Med Mol Imaging 38:441–450

    PubMed  CAS  Google Scholar 

  • Kiesewetter DO, Kilbourn MR, Landvatter SW, Heiman DF, Katzenellenbogen JA, Welch MJ (1984) Preparation of four fluorine- 18-labeled estrogens and their selective uptakes in target tissues of immature rats. J Nucl Med 25:1212–1221

    PubMed  CAS  Google Scholar 

  • Kikuchi M, Yamane T, Shinohara S, Fujiwara K, Hori SY, Tona Y, Yamazaki H, Naito Y, Senda M (2011) 18F-fluoromisonidazole positron emission tomography before treatment is a predictor of radiotherapy outcome and survival prognosis in patients with head and neck squamous cell carcinoma. Ann Nucl Med 25:625–633

    PubMed  CAS  Google Scholar 

  • Kizaka-Kondoh S, Konse-Nagasawa H (2009) Significance of nitroimidazole compounds and hypoxia-inducible factor-1 for imaging tumor hypoxia. Cancer Sci 100:1366–1373

    PubMed  CAS  Google Scholar 

  • Krasikova RN, Kuznetsova OF, Fedorova OS, Maleev VI, Saveleva TF, Belokon YN (2008) No carrier added synthesis of O-(2′-[18F]fluoroethyl)-l-tyrosine via a novel type of chiral enantiomerically pure precursor, NiII complex of a (S)-tyrosine schiff base. Biorg Med Chem 16:4994–5003

    CAS  Google Scholar 

  • Krohn KA, Mankoff DA, Eary JF (2001) Imaging cellular proliferation as a measure of response to therapy. J Clin Pharmacol Suppl:96S–103S

    Google Scholar 

  • Kryza D, Tadino V, Filannino MA, Villeret G, Lemoucheux L (2008) Fully automated [18F]fluorocholine synthesis in the TracerLab MX FDG Coincidence synthesizer. Nucl Med Biol 35:255–260

    PubMed  CAS  Google Scholar 

  • Kumar P, Mercer J, Doerkson C, Tonkin K, McEwan AJ (2007) Clinical production, stability studies and PET imaging with 16-α-[18F]fluoroestradiol ([18F]FES) in ER positive breast cancer patients. J Pharm Pharm Sci 10:256s–265s

    PubMed  CAS  Google Scholar 

  • Lee N, Nehmeh S, Schöder H, Fury M, Chan K, Ling CC, Humm J (2009) Prospective trial incorporating pre-/mid-treatment [18F]-misonidazole positron emission tomography for head-and-neck cancer patients undergoing concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys 75:101–108

    PubMed  CAS  Google Scholar 

  • Lee SJ, Oh SJ, Chi DY, Kil HS, Kim EN, Ryu JS, Moon DH (2007) Simple and highly efficient synthesis of 3′-deoxy-3′-[18F]fluorothymidine using nucleophilic fluorination catalyzed by protic solvent. Eur J Nucl Med Mol Imaging 34:1406–1409

    PubMed  CAS  Google Scholar 

  • Lee WC, Chang CH, Ho CL, Chen LC, Wu YH, Chen JT, Wang YL, Lee TW (2011) Early detection of tumor response by FLT/microPET Imaging in a C26 murine colon carcinoma solid tumor animal model. J Biomed Biotechnol 2011:535902

    PubMed  Google Scholar 

  • Li Z, Cai H, Conti PS (2011) Automated synthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-d-arabinofuranosyluracil ([18F]-FMAU) using a one reactor radiosynthesis module. Nucl Med Biol 38:201–206

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Lim JL, Zheng L, Berridge MS, Tewson TJ (1996) The use of 3-methoxymethyl-16 β, 17 β-epiestriol-O-cyclic sulfone as the precursor in the synthesis of F-18 16 α-fluoroestradiol. Nucl Med Biol 23:911–915

    PubMed  CAS  Google Scholar 

  • Luxen A, Guillaume M, Melega WP, Pike VW, Solin O, Wagner R (1992) Production of 6-[18F]fluoro-L-dopa and its metabolism in vivo–a critical review. Int J Rad Appl Instrum B 19:149–158

    PubMed  CAS  Google Scholar 

  • Machulla HJ, Blocher A, Kuntzsch M, Piert M, Wei R, Grierson JR (2000) Simplified Labeling Approach for Synthesizing 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT). Radioanal Nucl Chem 243:843–846

    CAS  Google Scholar 

  • Mamede M, Higashi T, Kitaichi M (2005) [18F]FDG uptake and PCNA, Glut-1, and hexokinase-II expressions in cancers and inflammatory lesions of the lung. Neoplasia 7:369–379

    PubMed  CAS  Google Scholar 

  • Mangner TJ, Klecker RW, Anderson L, Shields AF (2003) Synthesis of 2′-deoxy-2′-[18F]fluoro-β-d-arabinofuranosyl nucleosides, [18F]FAU, [18F]FMAU, [18F]FBAU and [18F]FIAU, as potential PET agents for imaging cellular proliferation. synthesis of [18F]labelled FAU, FMAU, FBAU. FIAU. Nucl Med Biol 30:215–224

    CAS  Google Scholar 

  • Mankoff DA, Tewson TJ, Eary JF (1997) Analysis of blood clearance and labeled metabolites for the estrogen receptor tracer [F-18]-16 α-fluoroestradiol (FES). Nucl Med Biol 24:341–348

    PubMed  CAS  Google Scholar 

  • Melega WP, Hoffman JM, Luxen A, Nissenson CH, Phelps ME, Barrio JR (1990) The effects of carbidopa on the metabolism of 6-[18F]fluoro-l-dopa in rats, monkeys and humans. Life Sci 47:149–157

    PubMed  CAS  Google Scholar 

  • Mittra E, Quon A (2009) Positron emission tomography/computed tomography: the current technology and applications. Radiol Clin North Am 47:147–160

    PubMed  Google Scholar 

  • Moulder JE, Rockwell S (1987) Tumor hypoxia: its impact on cancer therapy. Cancer Metastasis Rev 5:313–341

    PubMed  CAS  Google Scholar 

  • Mueller D, Klette I, Kalb F, Baum RP (2011) Synthesis of O-(2-[18F]fluoroethyl)-l-tyrosine based on a cartridge purification method. Nucl Med Biol 38:653–658

    PubMed  CAS  Google Scholar 

  • Muijs CT, Beukema JC, Widder J, van den Bergh AC, Havenga K, Pruim J, Langendijk JA (2011) 18F-FLT-PET for detection of rectal cancer. Radiother Oncol 98:357–359

    PubMed  Google Scholar 

  • Namavari M, Bishop A, Satyamurthy N, Bida G, Barrio JR (1992) Regioselective radiofluorodestannylation with [18F]F2 and [18F]CH3COOF: a high yield synthesis of 6-[18F]Fluoro-l-dopa. Int J Rad Appl Instrum A 43:989–996

    PubMed  CAS  Google Scholar 

  • Oh SJ, Chi DY, Mosdzianowski C, Kil HS, Ryu JS, Moon DH (2007) The automatic production of 16α-[18F]fluoroestradiol using a conventional [18F]FDG module with a disposable cassette system. Appl Radiat Isot 65:676–681

    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

    PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  • Oxender DL, Christensen HN (1963) Distinct mediating systems for the transport of neutral amino acids by the Ehrlich cell. J Biol Chem 238:3686–3699

    PubMed  CAS  Google Scholar 

  • Paolillo V, Riese S, Gelovani JG, Alauddin MM (2009) A fully automated synthesis of [18F]-FEAU and [18F]-FMAU using a novel dual reactor radiosynthesis module. J Label Compd Radiopharm 52:553–558

    CAS  Google Scholar 

  • Pascali G, D’Antonio L, Bovone P, Gerundini P, August T (2009) Optimization of automated large-scale production of [18F]fluoroethylcholine for PET prostate cancer imaging. Nucl Med Biol 36:569–574

    PubMed  CAS  Google Scholar 

  • Patrick GL (2005) An introduction in medicinal chemistry, 3rd edn. Oxford University Press, Oxford

    Google Scholar 

  • Patt M, Kuntzsch M, Machulla HJ (1999) Preparation of [18F]fluoromisonidazole by nucleophilic substitution on THP-protected precursor: Yield dependence on reaction parameters. J Radioanal Nucl Chem 240:925–927

    CAS  Google Scholar 

  • Pauleit D, Stoffels G, Schaden W, Hamacher K, Bauer D, Tellmann L, Herzog H, Bröer S, Coenen HH, Langen KJ (2005) PET with O-(2-18F-Fluoroethyl)-l-tyrosine in peripheral tumors: first clinical results. J Nucl Med 46:411–416

    PubMed  CAS  Google Scholar 

  • Peterson LM, Kurland BF, Link JM, Schubert EK, Stekhova S, Linden HM, Mankoff DA (2011) Factors influencing the uptake of 18F-fluoroestradiol in patients with estrogen receptor positive breast cancer. Nucl Med Biol 38:969–978

    PubMed  CAS  Google Scholar 

  • Peterson LM, Mankoff DA, Lawton T, Yagle K, Schubert EK, Stekhova S, Gown A, Link JM, Tewson T, Krohn KA (2008) Quantitative imaging of estrogen receptor expression in breast cancer with PET and 18F-fluoroestradiol. J Nucl Med 49:367–374

    PubMed  Google Scholar 

  • Piel M, Bauman A, Baum RP, Höhnemann S, Klette I, Wortmann R, Rösch F (2007) Improved automated synthesis of [18F]fluoroethylcholine as a radiotracer for cancer imaging. Bioorg Med Chem 15:3171–3175

    PubMed  CAS  Google Scholar 

  • Piert M, Machulla HJ, Picchio M, Reischl G, Ziegler S, Kumar P, Wester HJ, Beck R, McEwan AJ, Wiebe LI, Schwaiger M (2005) Hypoxia-specific tumor imaging with 18F-fluoroazomycin arabinoside. J Nucl Med 46:106–113

    PubMed  Google Scholar 

  • Podo F (1999) Tumour phospholipid metabolism. NMR Biomed 12:413–439

    PubMed  CAS  Google Scholar 

  • Poeppel TD, Krause BJ, Heusner TA, Boy C, Bockisch A, Antoch G (2009) PET/CT for the staging and follow-up of patients with malignancies. Eur J Radiol 70:382–392

    PubMed  CAS  Google Scholar 

  • Postema EJ, McEwan AJ, Riauka TA, Kumar P, Richmond DA, Abrams DN, Wiebe LI (2009) Initial results of hypoxia imaging using 1-α-D-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA). Eur J Nucl Med Mol Imaging 36:1565–1573

    PubMed  CAS  Google Scholar 

  • Rasey JS, Grunbaum Z, Magee S, Nelson NJ, Olive PL, Durand RE, Krohn KA (1987) Characterization of radiolabeled fluoromisonidazole as a probe for hypoxic cells. Radiat Res 111:292–304

    PubMed  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

    PubMed  CAS  Google Scholar 

  • Roels S, Slagmolen P, Nuyts J, Lee JA, Loeckx D, Maes F, Stroobants S, Penninckx F, Haustermans K (2008) Biological image-guided radiotherapy in rectal cancer: is there a role for FMISO or FLT, next to FDG? Acta Oncol 47:1237–1248

    PubMed  CAS  Google Scholar 

  • Roivainen A, Forsback S, Gronroos T, Lehikoinen P, Kahkonen M, Sutinen E, Minn H (2000) Blood metabolism of [methyl-11C]choline; implications for in vivo imaging with positron emission tomography. Eur J Nucl Med 27:25–32

    PubMed  CAS  Google Scholar 

  • Rose C, Thorpe SM, Andersen KW, Pedersen BV, Mouridsen HT, Blichert-Toft M, Rasmussen BB (1985) Beneficial effect of adjuvant tamoxifen therapy in primary breast cancer patients with high oestrogen receptor values. Lancet 1:16–19

    PubMed  CAS  Google Scholar 

  • Ross TL, Honer M, Lam PY, Mindt TL, Groehn V, Schibli R, Schubiger PA, Ametamey SM (2008) Fluorine-18 click radiosynthesis and preclinical evaluation of a new 18F-labeled folic acid derivative. Bioconjug Chem 19:2462–2470

    PubMed  CAS  Google Scholar 

  • Ross TL, Honer M, Müller C, Groehn V, Schibli R, Ametamey SM (2010) A new 18F-labeled folic acid derivative with improved properties for the PET imaging of folate receptor-positive tumors. J Nucl Med 51:1756–1762

    PubMed  CAS  Google Scholar 

  • Römer J, Füchtner F, Steinbach J, Johannsen B (1999) Automated production of 16α-[18F]fluoroestradiol for breast cancer imaging. Nucl Med Biol 26:473–479

    PubMed  Google Scholar 

  • Saier MH Jr, Daniels GA, Boerner P, Lin J (1988) Neutral amino acid transport systems in animal cells: potential targets of oncogene action and regulators of cellular growth. J Membr Biol 104:1–20

    PubMed  CAS  Google Scholar 

  • Schiesser M, Veit-Haibach P, Muller MK, Weber M, Bauerfeind P, Hany T, Clavien PA (2010) Value of combined 6-[18F]fluorodihydroxyphenylalanine PET/CT for imaging of neuroendocrine tumours. Br J Surg 97:691–697

    PubMed  CAS  Google Scholar 

  • Schober O, Heindel W (2008) PET-CT, 1st edn. Georg Thieme Verlag, Stuttgart

    Google Scholar 

  • Shao X, Hoareau R, Hockley BG, Tluczek LJ, Henderson BD, Padgett HC, Scott PJ (2011) Highlighting the versatility of the tracerlab synthesis modules. Part 1: fully automated production of [18F]labelled radiopharmaceuticals using a tracerlab FX(FN). J Labelled Comp Radiopharm 54:292–307

    PubMed  CAS  Google Scholar 

  • Shen B, Ehrlichmann W, Uebele M, Machulla HJ, Reischl G (2009) Automated synthesis of n.c.a. [18F]FDOPA via nucleophilic aromatic substitution with [18F]fluoride. Appl Radiat Isot 67:1650–1653

    PubMed  CAS  Google Scholar 

  • Sherley JL, Kelly TJ (1988) Regulation of human thymidine kinase during the cell cycle. J Biol Chem 263:8350–8358

    PubMed  CAS  Google Scholar 

  • Shields AF, Grierson JR, Dohmen BM, Machulla HJ, Stayanoff JC, Lawhorn-Crews JM, Obradovich JE, Muzik O, Mangner TJ (1998) Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nat Med 4:1334–1336

    PubMed  CAS  Google Scholar 

  • Shotwell A, Jayme DW, Killberg M, Oxender DL (1981) Neutral amino acid transport systems in Chinese hamster ovary cells. J Biol Chem 256:5422–5427

    PubMed  CAS  Google Scholar 

  • Smith TA (2000) Mammalian hexokinases and their abnormal expression in cancer. Br J Biomed Sci 57:170–178

    PubMed  CAS  Google Scholar 

  • Souba WW, Pacitti AJ (1992) How amino acids get into cells: mechanisms, models, menus and mediators. J Parenter Enteral Nutr 16:569–578

    CAS  Google Scholar 

  • Southworth R, Darling JL, Medina RA, Flynn AA, Pedley RB, Garlick PB (2002) Dissociation of glucose tracer uptake and glucose transporter distribution in the regionally ischemic isolated rat heart: application of a new autoradiographic technique. Eur J Nucl Med Mol Imaging 29:1334–1341

    PubMed  CAS  Google Scholar 

  • Sun H, Sloan A, Mangner TJ, Vaishampayan U, Muzik O, Collins JM, Douglas K, Shields AF (2005) Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer. Eur J Nucl Med Mol Imaging 32:15–22

    PubMed  CAS  Google Scholar 

  • Swanson KR, Chakraborty G, Wang CH, Rockne R, Harpold HL, Muzi M, Adamsen TC, Krohn KA, Spence AM (2009) Complementary but distinct roles for MRI and 18F-fluoromisonidazole PET in the assessment of human glioblastomas. J Nucl Med 50:36–44

    PubMed  Google Scholar 

  • Tang G, Tang X, Wen F, Wang M, Li B (2010) A facile and rapid automated synthesis of 3′-deoxy-3′-[18F]fluorothymidine. Appl Radiat Isot 68:1734–1739

    PubMed  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

    PubMed  CAS  Google Scholar 

  • Tewson TJ, Mankoff DA, Peterson LM, Woo I, Petra P (1999) Interactions of 16α-[18F]-fluoroestradiol (FES) with sex steroid binding protein (SBP). Nucl Med Biol 26:905–913

    PubMed  CAS  Google Scholar 

  • Thiele F, Ehmer J, Piroth MD, Eble MJ, Coenen HH, Kaiser HJ, Schaefer WM, Buell U, Boy C (2009) The quantification of dynamic FET PET imaging and correlation with the clinical outcome in patients with glioblastoma. Phys Med Biol 54:5525–5539

    PubMed  Google Scholar 

  • Tsujikawa T, Yoshida Y, Mori T, Kurokawa T, Fujibayashi Y, Kotsuji F, Okazawa H (2008) Uterine tumors: pathophysiologic imaging with 16α-[18F]fluoro-17β-estradiol and 18F fluorodeoxyglucose PET–initial experience. Radiology 248:599–605

    PubMed  Google Scholar 

  • Van de Wiele C, De Vos F, Slegers G, Van Belle S, Dierckx RA (2000) Radiolabeled estradiol derivatives to predict response to hormonal treatment in breast cancer: a review. Eur J Nucl Med 27:1421–1433

    PubMed  Google Scholar 

  • Veach DR, Namavari M, Pillarsetty N, Santos EB, Beresten-Kochetkov T, Lambek C, Punzalan BJ, Antczak C, Smith-Jones PM, Djaballah H, Clarkson B, Larson SM (2007) Synthesis and biological evaluation of a fluorine-18 derivative of dasatinib. J Med Chem 50: 5853–5857

    Google Scholar 

  • Wagner S, Breyholz HJ, Faust A, Höltke C, Levkau B, Schober O, Schäfers M, Kopka K (2006) Molecular imaging of matrix metalloproteinases in vivo using small molecule inhibitors for SPECT and PET. Curr Med Chem 13:2819–2838

    PubMed  CAS  Google Scholar 

  • Warburg O, Posener K, Negelein E (1924) VIII. The metabolism of cancer cells. Biochem Zeitschr 152:129–169

    Google Scholar 

  • Weckesser M, Langen KJ, Rickert CH, Kloska S, Straeter R, Hamacher K, Kurlemann G, Wassmann H, Coenen HH, Schober O (2005) O-(2-[18F]fluorethyl)-l-tyrosine PET in the clinical evaluation of primary brain tumours. Eur J Nucl Med Mol Imaging 32:422–429

    PubMed  CAS  Google Scholar 

  • Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219:316–333

    PubMed  CAS  Google Scholar 

  • Welch MJ, Redvanly CS (2003) Handbook of radiopharmaceuticals: radiochemistry and applications. Wiley, London

    Google Scholar 

  • Wester HJ, Herz M, Weber W, Heiss P, Senekowitsch-Schmidtke R, Schwaiger M, Stöcklin G (1999) Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-l-tyrosine for tumor imaging. J Nucl Med 40:205–212

    PubMed  CAS  Google Scholar 

  • Wodarski C, Eisenbarth J, Weber K, Henze M, Haberkorn U, Eisenhut M (2000) Synthesis of 3′-deoxy-3′-[18F]fluoro-thymidine with 2,3′-anhydro-5′-O-(4,4′-dimethoxytrityl)-thymidine. J Label Compd Radiopharm 43:1211–1218

    CAS  Google Scholar 

  • Yamamoto Y, Kameyama R, Izuishi K, Takebayashi R, Hagiike M, Asakura M, Haba R, Nishiyama Y (2009) Detection of colorectal cancer using 18F-FLT PET: comparison with 18F-FDG PET. Nucl Med Commun 30:841–845

    PubMed  Google Scholar 

  • Yoshida Y, Kurokawa T, Tsujikawa T, Okazawa H, Kotsuji F (2009) Positron emission tomography in ovarian cancer: 18F-deoxy-glucose and 16α-18F-fluoro-17β-estradiol PET. J Ovarian Res 2:7

    PubMed  Google Scholar 

  • Yun M, Oh SJ, Ha HJ, Ryu JS, Moon DH (2003) High radiochemical yield synthesis of 3′-deoxy-3′-[18F]fluorothymidine using (5′-O-dimethoxytrityl-2′-deoxy-3′-O-nosyl-β-D-threo pentofuranosyl)thymine and its 3-N-BOC-protected analogue as a labeling precursor. Nucl Med Biol 30:51–157

    Google Scholar 

  • Zhang L, Tang G, Yin D, Tang X, Wang Y (2002) Enantioselective synthesis of no-carrier-added (NCA) 6-[18F]fluoro-l-DOPA. Appl Radiat Isot 57:145–151

    PubMed  CAS  Google Scholar 

  • Zuhayra M, Alfteimi A, Forstner CV, Lützen U, Meller B, Henze E (2009) New approach for the synthesis of [18F]fluoroethyltyrosine for cancer imaging: simple, fast, and high yielding automated synthesis. Bioorg Med Chem 17:7441–7448

    PubMed  CAS  Google Scholar 

  • Zuhayra M, Alfteimi A, Papp L, Lützen U, Lützen A, Von Forstner C, Meller B, Henze E (2008) Simplified fast and high yielding automated synthesis of [18F]fluoroethylcholine for prostate cancer imaging. Bioorg Med Chem 16:9121–9126

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany

    Stefan Wagner & Klaus Kopka

Authors
  1. Stefan Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Kopka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefan Wagner .

Editor information

Editors and Affiliations

  1. Klinik für Nuklearmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Münster, 48149, Germany

    Otmar Schober

  2. Klinik für Nuklearmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Str. 33, Münster, 48129, Germany

    Burkhard Riemann

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Wagner, S., Kopka, K. (2013). Non-peptidyl 18F-Labelled PET Tracers as Radioindicators for the Noninvasive Detection of Cancer. In: Schober, O., Riemann, B. (eds) Molecular Imaging in Oncology. Recent Results in Cancer Research, vol 187. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-10853-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-10853-2_3

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-10852-5

  • Online ISBN: 978-3-642-10853-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation