Positron emission tomography (PET) imaging with (18)F-based radiotracers.

Positron Emission Tomography (PET) is a nuclear medicine imaging technique that is widely used in early detection and treatment follow up of many diseases, including cancer. This modality requires positron-emitting isotope labeled biomolecules, which are synthesized prior to perform imaging studies. Fluorine-18 is one of the several isotopes of fluorine that is routinely used in radiolabeling of biomolecules for PET; because of its positron emitting property and favorable half-life of 109.8 min. The biologically active molecule most commonly used for PET is 2-deoxy-2-(18)F-fluoro-β-D-glucose ((18)F-FDG), an analogue of glucose, for early detection of tumors. The concentrations of tracer accumulation (PET image) demonstrate the metabolic activity of tissues in terms of regional glucose metabolism and accumulation. Other tracers are also used in PET to image the tissue concentration. In this review, information on fluorination and radiofluorination reactions, radiofluorinating agents, and radiolabeling of various compounds and their application in PET imaging is presented.

[1]  M. Raggi,et al.  Benzodiazepine metabolism: an analytical perspective. , 2008, Current drug metabolism.

[2]  P. Conti,et al.  9-[(3-[18F]-fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]-FHPG): a potential imaging agent of viral infection and gene therapy using PET. , 1996, Nuclear medicine and biology.

[3]  W. Bornmann,et al.  Detection of Pancreatic Carcinomas by Imaging Lactose-Binding Protein Expression in Peritumoral Pancreas Using [18F]Fluoroethyl-Deoxylactose PET/CT , 2009, PloS one.

[4]  W. Mcbride,et al.  Improved 18F labeling of peptides with a fluoride-aluminum-chelate complex. , 2010, Bioconjugate chemistry.

[5]  S. Gambhir,et al.  Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's expression. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  E. Hoffman,et al.  A positron-emission transaxial tomograph for nuclear imaging (PETT). , 1975, Radiology.

[7]  J. M. Roe,et al.  Solid-state forms of paroxetine hydrochloride , 1988 .

[8]  P. Conti,et al.  Expedient synthesis of [18F]-labeled α-trifluoromethyl ketones , 2003 .

[9]  W. Bornmann,et al.  Synthesis and Ex Vivo Autoradiographic Evaluation of Ethyl-β-d-galactopyranosyl-(1,4′)-2′-deoxy-2′-[18F]fluoro-β-d-glucopyranoside—A Novel Radioligand for Lactose-Binding Protein: Implications for Early Detection of Pancreatic Carcinomas with PET , 2011, Molecular Imaging and Biology.

[10]  C. Dence,et al.  Monitoring of therapy in androgen-dependent prostate tumor model by measuring tumor proliferation. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[11]  V J Lowe,et al.  Detection of primary and recurrent lung cancer by means of F-18 fluorodeoxyglucose positron emission tomography (FDG PET). , 1995, The Journal of thoracic and cardiovascular surgery.

[12]  P. Conti,et al.  Synthesis of 2'-deoxy-2'-[18F]fluoro-5-bromo-1-beta-D-arabinofuranosyluracil ([18F]-FBAU) and 2'-deoxy-2'-[18F]fluoro-5-chloro-1-beta-D-arabinofuranosyl-uracil ([18F]-FCAU), and their biological evaluation as markers for gene expression. , 2004, Nuclear medicine and biology.

[13]  P. Conti,et al.  A general synthesis of 2'-deoxy-2'-[18F]fluoro-1-β-D-arabinofuranosyluracil and its 5-substituted nucleosides , 2003 .

[14]  D. Schlyer.  Production of Radionuclides in Accelerators , 2005 .

[15]  Charles M. Starks,et al.  PHASE – TRANSFER CATALYSIS. I. HETEROGE NEOUS REACTIONS INVOLVING ANION TRANSFER BY QUATERNARY AMMONIUM AND PHOSPHONIUM SALTS , 1971 .

[16]  U. Haberkorn,et al.  Synthesis of 3′‐deoxy‐3′‐[18F]fluoro‐thymidine with 2,3′‐anhydro‐5′‐O‐(4,4′‐dimethoxytrityl)‐thymidine , 2000 .

[17]  R. van Furth,et al.  A prospective study of the efficacy of fluconazole (UK-49,858) against deep-seated fungal infections. , 1988, The Journal of antimicrobial chemotherapy.

[18]  A. Wolf,et al.  Absolute Cross Sections for the Production of 18F via the 18O(p, n)18F Reaction , 1979 .

[19]  Kinetics and Applications of F-18-Fluorouracil in Colorectal Tumors , 1995 .

[20]  E. Aboagye,et al.  Early detection of tumor response to chemotherapy by 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography: the effect of cisplatin on a fibrosarcoma tumor model in vivo. , 2005, Cancer research.

[21]  P. Conti,et al.  Direct comparison of radiolabeled probes FMAU, FHBG, and FHPG as PET imaging agents for HSV1-tk expression in a human breast cancer model. , 2004, Molecular imaging.

[22]  J. Gelovani,et al.  Radiosynthesis of 6-([18F]fluoroacetamido)-1-hexanoic-anilide ([18F]FAHA) for PET imaging of histone deacetylase (HDAC) , 2006 .

[23]  H. Dittmann,et al.  Early changes in [18F]FLT uptake after chemotherapy: an experimental study , 2002, European Journal of Nuclear Medicine and Molecular Imaging.

[24]  V. Ponomarev,et al.  A Human-Derived Reporter Gene for Noninvasive Imaging in Humans: Mitochondrial Thymidine Kinase Type 2 , 2007, Journal of Nuclear Medicine.

[25]  W. Arap,et al.  A preclinical model for predicting drug response in soft-tissue sarcoma with targeted AAVP molecular imaging , 2008, Proceedings of the National Academy of Sciences.

[26]  Y Yonekura,et al.  In vivo assessment of glucose metabolism in hepatocellular carcinoma with FDG-PET. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[27]  K. Ogawa,et al.  Radiosynthesis and Initial In Vitro Evaluation of [18F]F-PEG6-IPQA—A Novel PET Radiotracer for Imaging EGFR Expression-Activity in Lung Carcinomas , 2011, Molecular Imaging and Biology.

[28]  A. Luxen,et al.  Production of 6-[18F]fluoro-L-dopa and its metabolism in vivo--a critical review. , 1992, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[29]  David J. Yang,et al.  Handbook of Radiopharmaceuticals: Radiochemistry and Applications , 2004 .

[30]  H. Machulla,et al.  Preparation of [18F]fluoromisonidazole by nucleophilic substitution on THP-protected precursor: Yield dependence on reaction parameters , 1999 .

[31]  P. Conti,et al.  Synthesis and preliminary evaluation of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG): a new potential imaging agent for viral infection and gene therapy using PET. , 1998, Nuclear medicine and biology.

[32]  S. Cherry,et al.  Synthesis of 8-[18F]fluoroguanine derivatives: in vivo probes for imaging gene expression with positron emission tomography ☆ , 2000 .

[33]  W. Bornmann,et al.  Molecular–Genetic PET Imaging Using an HSV1-tk Mutant Reporter Gene with Enhanced Specificity to Acycloguanosine Nucleoside Analogs , 2009, Journal of Nuclear Medicine.

[34]  W. Mcbride,et al.  A Novel Method of 18F Radiolabeling for PET , 2009, Journal of Nuclear Medicine.

[35]  J. Bading,et al.  Preclinical evaluation of the penciclovir analog 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine for in vivo measurement of suicide gene expression with PET. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[36]  R. Chirakal,et al.  Aromatic radiofluorination with [18F]fluorine gas: 6-[18F]fluoro-L-dopa. , 1984, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[37]  P. Conti,et al.  Biodistribution and PET imaging of [(18)F]-fluoroadenosine derivatives. , 2007, Nuclear medicine and biology.

[38]  J. Yeo,et al.  Fully automated synthesis system of 3'-deoxy-3'-[18F]fluorothymidine. , 2004, Nuclear medicine and biology.

[39]  D. O'Hagan.  Understanding Organofluorine Chemistry. An Introduction to the C—F Bond , 2008 .

[40]  J. Holden,et al.  Reproducibility and discriminating ability of fluorine-18-6-fluoro-L-Dopa PET in Parkinson's disease. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[41]  A. Luxen,et al.  Recommendations for fluorine-18 production , 1991 .

[42]  U. Haberkorn,et al.  A new precursor for the radiosynthesis of [18F]FLT. , 2002, Nuclear medicine and biology.

[43]  Jae Seung Kim,et al.  [18F]3′-deoxy-3′-fluorothymidine PET for the diagnosis and grading of brain tumors , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[44]  T. Mattfeldt,et al.  Molecular imaging of proliferation in malignant lymphoma. , 2006, Cancer research.

[45]  B. Pate,et al.  Routine synthesis of L-[18F]6-fluorodopa with fluorine-18 acetyl hypofluorite. , 1986, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[46]  D. Visvikis,et al.  Assessment of recurrent colorectal cancer following 5-fluorouracil chemotherapy using both 18FDG and 18FLT PET , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[47]  W. Oyen,et al.  A Novel Facile Method of Labeling Octreotide with 18F-Fluorine , 2010, Journal of Nuclear Medicine.

[48]  V. M. Vlasov.  Fluoride ion as a nucleophile and a leaving group in aromatic nucleophilic substitution reactions , 1993 .

[49]  W. Mcbride,et al.  High-yielding aqueous 18F-labeling of peptides via Al18F chelation. , 2011, Bioconjugate chemistry.

[50]  M. Welch,et al.  Positron emission tomography with 2-[18F]Fluoro-2-deoxy-D-glucose and 16alpha-[18F]fluoro-17beta-estradiol in breast cancer: correlation with estrogen receptor status and response to systemic therapy. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[51]  J. Galgiani,et al.  Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo , 1986, Antimicrobial Agents and Chemotherapy.

[52]  P. Conti,et al.  Synthesis of [18F]‐labeled 2′‐deoxy‐2′‐fluoro‐5‐methyl‐1‐β‐D‐arabinofuranosyluracil ([18F]‐FMAU) , 2002 .

[53]  G Brix,et al.  Assessment of the biodistribution and metabolism of 5-fluorouracil as monitored by 18F PET and 19F MRI: a comparative animal study. , 1996, Nuclear medicine and biology.

[54]  Sanjiv S Gambhir,et al.  A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[55]  C. Hsieh,et al.  A high yield robotic synthesis of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) and 9-[3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F] FHPG) for gene expression imaging. , 2007, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[56]  G. Bormans,et al.  Synthesis and biological evaluation of carbon-11- and fluorine-18-labeled 2-oxoquinoline derivatives for type 2 cannabinoid receptor positron emission tomography imaging. , 2009, Nuclear medicine and biology.

[57]  G. Hutchins,et al.  Novel radiosynthesis of PET HSV-tk gene reporter probes [18F]FHPG and [18F]FHBG employing dual Sep-Pak SPE techniques. , 2003, Bioorganic & medicinal chemistry letters.

[58]  M. Reivich,et al.  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 , 1978 .

[59]  C. Dence,et al.  Rapid and reproducible radiosynthesis of [18F] FHBG. , 2004, Nuclear medicine and biology.

[60]  V. Pike,et al.  Synthesis of [F]Xenon Difluoride as a Radiolabeling Reagent from [F]Fluoride Ion in a Micro-reactor and at Production Scale. , 2010, Journal of fluorine chemistry.

[61]  A. Wolf,et al.  Cyclotron isotopes and radiopharmaceuticals— XXV An anhydrous 18F-fluorinating intermediate: Trifluoromethyl hypofluorite☆ , 1978 .

[62]  H. Hricak,et al.  A New Acycloguanosine-Specific Supermutant of Herpes Simplex Virus Type 1 Thymidine Kinase Suitable for PET Imaging and Suicide Gene Therapy for Potential Use in Patients Treated with Pyrimidine-Based Cytotoxic Drugs , 2008, Journal of Nuclear Medicine.

[63]  Ming-fang Wang,et al.  Fully automated one-pot synthesis of [18F]fluoromisonidazole. , 2005, Nuclear medicine and biology.

[64]  J. Gelovani,et al.  Radiosynthesis of 1′-[18F]fluoroethyl-β-D-lactose ([18F]-FEL) for early detection of pancreatic carcinomas with PET , 2011 .

[65]  J. Powers,et al.  Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[66]  Y. Fujibayashi,et al.  Alkyl-fluorinated thymidine derivatives for imaging cell proliferation II. Synthesis and evaluation of N3-(2-[18F]fluoroethyl)-thymidine. , 2006, Nuclear medicine and biology.

[67]  Dae Hyuk Moon,et al.  High radiochemical yield synthesis of 3'-deoxy-3'-[18F]fluorothymidine using (5'-O-dimethoxytrityl-2'-deoxy-3'-O-nosyl-beta-D-threo pentofuranosyl)thymine and its 3-N-BOC-protected analogue as a labeling precursor. , 2003, Nuclear medicine and biology.

[68]  Y. Yonekura,et al.  New approach to fully automated synthesis of sodium [18F]fluoroacetate -- a simple and fast method using a commercial synthesizer. , 2006, Nuclear medicine and biology.

[69]  E. Hoffman,et al.  Application of annihilation coincidence detection to transaxial reconstruction tomography. , 1975, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[70]  J. Bading,et al.  Blocking catabolism with eniluracil enhances PET studies of 5-[18F]fluorouracil pharmacokinetics. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[71]  L. Bidaut,et al.  Pharmacokinetics, Metabolism, Biodistribution, Radiation Dosimetry, and Toxicology of 18F-Fluoroacetate (18F-FACE) in Non-human Primates , 2012, Molecular Imaging and Biology.

[72]  O. Mawlawi,et al.  Evaluation of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-l-arabinofuranosyluracil ([18F]-l-FMAU) as a PET imaging agent for cellular proliferation: comparison with [18F]-d-FMAU and [18F]FLT , 2008, European Journal of Nuclear Medicine and Molecular Imaging.

[73]  G. Peters,et al.  18F-radiopharmacokinetics of [18F]-5-fluorouracil in a mouse bearing two colon tumors with a different 5-fluorouracil sensitivity: a study for a correlation with oncological results. , 1996, Nuclear medicine and biology.

[74]  Chih-Hsien Chang,et al.  Biodistribution, pharmacokinetics and PET imaging of [(18)F]FMISO, [(18)F]FDG and [(18)F]FAc in a sarcoma- and inflammation-bearing mouse model. , 2009, Nuclear medicine and biology.

[75]  J. Gelovani,et al.  Synthesis of [18F]-labeled N-3(substituted) thymidine analogues : N-3([18F]fluorobutyl) thymidine ([18F]-FBT) and N-3([18F]fluoropentyl) thymidine ([18F]-FPT) for PET , 2006 .

[76]  S. Yu,et al.  Review of 18F-FDG Synthesis and Quality Control , 2006, Biomedical Imaging and Intervention Journal.

[77]  A. Alavi,et al.  A simplified one-pot synthesis of 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy. , 2001, Nuclear medicine and biology.

[78]  E. Årstad,et al.  Synthesis and reactivity of [18F]-N-fluorobenzenesulfonimide. , 2007, Chemical communications.

[79]  J. M. Ollinger,et al.  Positron Emission Tomography , 2018, Handbook of Small Animal Imaging.

[80]  Judith E. Flores,et al.  PET of Glial Metabolism Using 2-18F-Fluoroacetate , 2009, Journal of Nuclear Medicine.

[81]  P. Pedersen,et al.  High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[82]  R. Sweet,et al.  Blood glucose levels during methoxyflurane anaesthesia , 1964, Canadian Anaesthetists' Society journal.

[83]  D. Paik,et al.  Noninvasive detection of therapeutic cytolytic T cells with 18F–FHBG PET in a patient with glioma , 2009, Nature Clinical Practice Oncology.

[84]  S. Stanford,et al.  Prozac: panacea or puzzle? , 1996, Trends in pharmacological sciences.

[85]  C. Mathis,et al.  A radiosynthesis of fluorine-18 fluoromisonidazole. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[86]  O. Muzik,et al.  Imaging DNA synthesis in vivo with 18F-FMAU and PET. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[87]  Zhanhong Wu,et al.  Semiautomatic synthesis of 3'-deoxy-3'-[18F]fluorothymidine using three precursors. , 2006, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[88]  J. Gelovani,et al.  A novel method for stereospecific fluorination at the 2′-arabino-position of pyrimidine nucleoside: synthesis of [18F]-FMAU , 2010 .

[89]  J. Barrio,et al.  Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[90]  J. C. Matthews,et al.  Plasma pharmacokinetic evaluation of cytotoxic agents radiolabelled with positron emitting radioisotopes , 2008, Cancer Chemotherapy and Pharmacology.

[91]  W. Wilson,et al.  Mefloquine, a clinically useful quinolinemethanol antimalarial which does not significantly bind to DNA , 1975, Nature.

[92]  Mark Muzi,et al.  Kinetic analysis of 3'-deoxy-3'-fluorothymidine PET studies: validation studies in patients with lung cancer. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[93]  S. Cherry,et al.  Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Mariana Adam,et al.  Synthesis and purification of ?-6-[18F]fluorodopa , 1988 .

[95]  J. Gelovani,et al.  N3-Substituted Thymidine Analogues: Radiosyntheses of N3-[4-(4-(2-[18F] fluoroethyl)phenyl)butyl]thymidine and N3-[5-(4-(2-[18F]fluoroethyl)- phenyl)pentyl]thymidine for PET , 2009 .

[96]  C. Lilley,et al.  A Hybrid Vector for Ligand-Directed Tumor Targeting and Molecular Imaging , 2006, Cell.

[97]  O. Muzik,et al.  Tumor Imaging Using 1-(2′-deoxy-2′-18F- Fluoro-β-d-Arabinofuranosyl)Thymine and PET , 2007, Journal of Nuclear Medicine.

[98]  Nobuyuki Oyama,et al.  18F-fluoroacetate: a potential acetate analog for prostate tumor imaging--in vivo evaluation of 18F-fluoroacetate versus 11C-acetate. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[99]  O. Muzik,et al.  Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[100]  H. Björk,et al.  Preparation of fluorine‐18‐labelled fluoromisonidazole using two different synthesis methods , 2004 .

[101]  M J Welch,et al.  Synthesis and biodistribution of 18F-labeled fluoronitroimidazoles: potential in vivo markers of hypoxic tissue. , 1986, International journal of radiation applications and instrumentation. Part A, Applied radiation and isotopes.

[102]  E. Munson,et al.  Enflurane, Isoflurane, and Halothane and Isolated Human Uterine Muscle , 1977, Anesthesiology.

[103]  S. Gambhir,et al.  PET imaging of herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk reporter gene expression in mice and humans using [18F]FHBG , 2006, Nature Protocols.

[104]  A. Wolf,et al.  ANHYDROUS 18F LABELED ELEMENTAL FLUORINE FOR RADIOPHARMACEUTICAL PREPARATION , 1981 .

[105]  A. Karlström,et al.  Evaluation of a maleimido derivative of NOTA for site-specific labeling of affibody molecules. , 2011, Bioconjugate chemistry.

[106]  J. Clark.  Fluoride ion as a base in organic synthesis , 1980 .

[107]  D. Lee,et al.  Synthesis of no-carrier-added [18F]fluoroacetate , 1997 .

[108]  P. Conti,et al.  Synthesis of [18F]‐labeled adenosine analogues as potential PET imaging agents , 2003 .

[109]  C. Nanni,et al.  Experimental results and related clinical implications of PET detection of epidermal growth factor receptor (EGFr) in cancer. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[110]  J. Wesseling,et al.  Comparison of 18F-FLT PET and 18F-FDG PET in esophageal cancer. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[111]  Lester J. Peters,et al.  Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent , 2005, European Journal of Nuclear Medicine and Molecular Imaging.

[112]  W. Wolf,et al.  Synthesis of 3'-fluoro-3'-deoxythymidine and studies of its 18F-radiolabeling, as a tracer for the noninvasive monitoring of the biodistribution of drugs against AIDS , 1991 .

[113]  C. Solbach,et al.  Simplified, automated synthesis of 3′[18F]fluoro-3′-deoxy-thymidine ([18F]FLT) and simple method for metabolite analysis in plasma , 2006 .

[114]  J. Gelovani,et al.  N(3)-Substituted thymidine analogues V: synthesis and preliminary PET imaging of N(3)-[(18)F]fluoroethyl thymidine and N(3)-[(18)F]fluoropropyl thymidine. , 2008, Nuclear medicine and biology.

[115]  H. Kolb,et al.  Radiosynthesis of 3′‐Deoxy‐3′‐[18F]Fluorothymidine ([18F]FLT) , 2012 .

[116]  S. Hain,et al.  2-Fluorine-18-fluoro-2-deoxy-D glucose positron emission tomography in the pretreatment staging of Hodgkin's disease: influence on patient management in a single institution. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[117]  J. Barrio,et al.  A fully automated one pot synthesis of 9-(4-[18F]fluoro-3-hydroxymethylbutyl) guanine for gene therapy studies. , 2002, Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging.

[118]  J. Gelovani,et al.  Synthesis of 3′‐deoxy‐3′‐[18F]fluoro‐1‐β‐D‐xylofuranosyluracil ([18F]‐FMXU) for PET , 2005 .

[119]  R. Blasberg,et al.  Comparison of radiolabeled nucleoside probes (FIAU, FHBG, and FHPG) for PET imaging of HSV1-tk gene expression. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[120]  Y. Fujibayashi,et al.  Alkyl-fluorinated thymidine derivatives for imaging cell proliferation I. The in vitro evaluation of some alkyl-fluorinated thymidine derivatives. , 2006, Nuclear medicine and biology.

[121]  B. Braakhuis,et al.  An optimized synthesis of 18F-labelled 5-fluorouracil and a reevaluation of its use as a prognostic agent , 2004, European Journal of Nuclear Medicine.

[122]  P. Conti,et al.  Stereospecific fluorination of 1,3,5-tri-O-benzoyl-α-D-ribofuranose-2-sulfonate esters: Preparation of a versatile intermediate for synthesis of 2′-[ 18F ]-fluoro-arabinonucleosides , 2000 .

[123]  J. R. Grierson,et al.  Simplified Labeling Approach for Synthesizing 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) , 2000 .

[124]  N. Volkow,et al.  Evaluation of 6-([(18)F]fluoroacetamido)-1-hexanoicanilide for PET imaging of histone deacetylase in the baboon brain. , 2009, Nuclear medicine and biology.

[125]  Otto Muzik,et al.  Imaging proliferation in vivo with [F-18]FLT and positron emission tomography , 1998, Nature Medicine.