positron emission tomography; gene expression; fluorinated analogs of nucleosides
Abstract :
[en] F-18-FDG is currently the only fluorinated tracer used in routine clinical positron emission tomography (PET). Fluorine 18 is considered as the ideal radioisotope for PET, thanks to a low positron energy, which not only limits the dose rate to the patients but also provides high-resolution images. Furthermore, the 110 min. physical half-life allows for high-yield radiosynthesis, transport from the production site to the imaging site, and imaging protocols that could span hours, which permits dynamic studies and assessing metabolic processes that may be fairly slow Recently, synthesis of fluorinated tracers from prosthetic group precursors, which allows easier radiolabeling of biomolecules, has given a boost to the development of numerous fluorinated tracers, Given the wide availability of fluorine 18, such tracers may well develop into important routine tracers. This article is a review of the literature concerning fluorinated analogs of nucleosides and fluorinated radiotracers of gene expression recently developed and under investigation.
Disciplines :
Oncology Radiology, nuclear medicine & imaging
Author, co-author :
Couturier, Olivier; Hôtel-Dieu (Nantes) > Service de médecine nucléaire
Chatal, Jean-François; Hôtel-Dieu (Nantes) > Service de médecine nucléaire
Hustinx, Roland ; Université de Liège - ULiège > Département des sciences cliniques > Médecine nucléaire
Language :
English
Title :
Fluorinated analogs of nucleosides and fluorinated tracers of gene expression for positron emission tomography
Alavi A, Reivich M. Guest editorial: the conception of FDG-PET imaging. Semin Nucl Med 2002 ; 32 : 2-5.
Warburg O. On the origin of cancer cells. Science 1956 ; 123 : 309-14.
Warburg O. The metabolism of tumors. London : Arnold Constable; 1930.
Schirrmeister H, Kuhn H, Guhlmann A, et al. Immunoscaging in pancreatic cancer and chronic active pancreatitis : does in vivo FDG-uptake correlate with proliferative activity? J Nucl Med 2001 ; 42 ; 721-5.
Kubota R, Kubota K, Yamada S, et al. Intratumoral distribution of fluorine-18-fluorodesoxyglucose in vivo: high accumulation in macrophages and granularion tissues studied by microautoradiography. J Nucl Med 1992 ; 33 : 1972-80.
Brown RS, Leung JY, Fisher SJ, et al. Intratumoral distribution of tritiared fluorodesoxyglucose in breast carcinoma I. Are inflammatory cells important? J Nuclear Med 1995 ; 36 ; 1854-61.
Higashi K, Clavo AC, Wahl RL. In vitro assessment of 2-fluoro-2-desoxy-D- glucose, L-methionine and rhymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. J Nuclear Med 1993 ; 34 : 773-9.
Lewis P, Salama A. Uptake of fluorine-18-fluorodesoxyglucose in sarcoidosis. J Nucl Med 1994 ; 35 : 1647-9.
Minn H, Clavo AC, Grenman R, et al. In vicro comparison of cell proliferation kinetics and uptake of tritiated fluorodesoxyglucose and L-methionine in squamous-cell carcinoma of the head and neck. J Nuclear Med 1995 ; 36 : 252-8.
Patz EF, Lowe VJ, Hoffman JM, et al. Focal pulmonary abnormalities: evaluation with F-18 fluorodesoxyglucose PET scanning. Radiology 1993 ; 188: 487-90.
Eary J, Mankoff D, Spence A, et al. 2-[C-11]thymidine imaging of malignant brain tumors. Cancer Res 1999 ; 59 : 615-21.
Shields A, Grierson J, Dohmen B, et al. Imaging proliferation in vivo with [F-18]FLT and positron emission tomography. Nature Med 1998 ; 4 : 1334-6.
Nimmagadda S, Mangner TJ, Muzik O, et al. Metabolic studies of F-18-FBAU in dogs: A PET tracer for DNA synthesis. J Nuclear Med 2002 ; 43 : 94.
Wang H, Oliver P, Nan L, et al. Radiolabeled 2′-fluorodesoxyuracil- beta-D-arabinofuranoside (FAU) and 2′-fluoro-5-methyldesoxyuracil-beta -D-arabinofutanoside (FMAU) as tumor- imaging agents in mice. Cancer Chemother Pharmacol 2002 ; 49 : 419-24.
Kong X, Zhu Q, Vidal P, et al. Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3′-fluoro-3′-desoxythymidine and 3′-azido-3′-désoxythymidine. Antimicrob Agents Chemother 1992 ; 36 : 808-18.
Wilson I, Chatterjee S, Wolf W. The use of 3′-fluoro-3′- désoxythymidine and studies of its 18F-radiolabeling, as a tracer for the non-invasive monitoring of the biodistribution of drugs against AIDS. J Fluorine Chem 1991 ; 55 : 283-9.
Martin S, Eisenbarth J, Wagner-Utermann U, et al. [18F]FLT. 18F labeling of 3-Boc-1-(2-desoxy-3-O-nosyl-5-O-trityl-b-D-lyxofuranosyl)thymine and other thymine derivatives. J Nucl Med 2000 ; 41(255P).
Martin S, Eisenbarth J, Wagner-Utermann U, et al. A new precursor for the radiosynthesis of [18F]FLT. Nucl Med Biol 2002 ; 29 : 263-73.
Belt J, Marina N, Phelps D, et al. Nucleoside transport in normal and neoplastic cells. Adv Enzyme Regul 1993 ; 33 : 235-52.
Coppock D, Pardee A. Control of thymidine kinase mRNA during the cell cycle. Mol Cell Biol 1987 ; 7 : 2925-32.
Gross M, Merrill G. Regulation of thymidine kinase protein levels during myogenic withdrawal from the cell cycle is independent of mRNA regulation. Nucleic Acids Res 1988 ; 16 : 11625-43.
Sherley J, Kelly T. Regulation of human thymidine kinase during the cell cycle. J Biol Chem 1988 ; 263 : 8350-8.
Ito M, Conrad S. Independent regulation of thymidine kinase mRNA and enzyme levels in serum-stimulated cells. J Biol Chem 1990 ; 265 : 6954-60.
Bartrek J, Bartkova J, Lukas J. The retinoblastoma protein pathway and the restriction point. Current Opin Cell Biol 1996 ; 8 : 805-14.
Ewen M. The cell cycle and the retinoblastoma protein family. Cancer Metastasis Rev 1994 ; 13 : 45-66.
Sherr C, Roberts J. Inhibitors of mammalian G1 cycline-dependent kinases. Genes Develop 1995 ; 9 : 1149-63.
Weinberg R. The retinoblastoma protein and cell cycle control. Cell 1995 ; 81 : 323-30.
Hengstchlager M, Knofler M, Mullner E, et al. Different regulation of thymidine kinase during the cell cycle of normal versus DNA tumor virus-transformed cells. J Biol Chem 1994 ; 269 : 1386-1342.
Hengstchlager M, Oliver P, Hengstshlager-Ottnad E, et al. Loss of the p16/MTS1 tumor suppressor gene causes E2F-mediated deregulation of essential enzymes of the DNA precursor metabolism. DNA Cell Biol 1996 ; 15 : 41-51.
Hengstchlager M, Hengstshlager-Ottnad E, Oliver P, et al. The role of p16 in the E2F-dependent thymidine kinase regulation. Oncogene 1996 ; 12 : 1635-43.
Romain S, Martin P, Klijn J, et al. DNA-synthesis enzyme activity: a biological tool useful for predicting anti-metabolic drug sensitivity in breast cancer? Int J Cancer 1997 ; 74 : 156-61.
Sakamoto S, Ebuchi M, Iwama T. Relative activities of thymidylate synthetase and thymidine kinase in human mammary tumours. Anticancer Res 1993 ; 13 : 205-7.
Toyohara J, Waki A, Takamatsu S, et al. Basis of FLT as cell proliferattion marker : comparative uptake studies with [3H]thymidine and [3H]arabinothymidine, and cell-analysis in 22 asynchronously growing tumor cell lines. Nucl Med Biol 2002 ; 29 : 281-7.
Grierson J, Vesselle H, Hofstrand P, et al. Comparative uptake and cell cycle measurements with [18F]FLT vs. [3H]thymidine in mammalian tumor cells. J Nucl Med 1998 ; 39 (Supp. 51) : 229P-230P.
Rasey J, Grierson J. 3′-désoxy-3′-[F-18] fluorothymidine(FLT) predicts changes in cell proliferation. J Nucl Med 1999 ; 40 (Suppl.) : 25P.
Rasey J, Grierson J, Wiens L, et al. Uptake of labeled FLT correlates with thymidine kinase (TK1) activity in human tumor cells. J Nucl Med 2000 ; 41 (Suppl.) : 36P-37P.
Eriksson S, Kierdaszuk B, Mucnh-Peterson B, et al. Comparison of the substate specificities of human thymidiine kinase 1 and 2 and desoxycytidine kinase toward antiviral and cytostatic nucleoside analogs. Biochem Biophys Res Commun 1991 ; 176 : 586-92.
Nottebrock H, Then R. Thymidine concentrations in serum and urine of different animal species and man. Biochem Pharmacol 1977 ; 26 : 2175-9.
Buck AK, Schirrmeister H, Hetzel M, et al. 3-desoxy-3-[(18)F] fluorothymidine-positron emission tomography for noninvasive assessment of proliferation in pulmonary nodules. Cancer Res 2002 ; 62 : 3331-4.
Buck AK, Halter G, Schirrmeister H, et al. Imaging proliferation in lung tumors with PET. 18F-FLT versus 18F-FDG. J Nucl Med 2003 ; 44 : 1426-31.
Dittmann H, Dohmen BM, Pauken F, et al. [18F]FLT PET for diagnosis and staging of thoracic tumours. Eur J Nucl Med Mol Imaging 2003 ; 30 : 1407-12.
Francis DL, Visvikis D, Costa DC, et al. Potential impact of [18F]3′-desoxy-3′-fluorothymidine versus [18F]nuoro-2-desoxy-D- glucose in positron emission tomography for colorectal cancer. Eur J Nucl Med Mol Imaging 2003 ; 30 : 988-94.
Barthel H, Cleij MC, Collingridge DR, et al. 3′-desoxy-3′- [18F]fluorothymidine as a new marker for monitoring tumor response to antiproliferative therapy in vivo with positron emission tomography. Cancer Res 2003 ; 63 : 3791-8.
Dittmann H, Dohmen BM, Kehlbach R, et al. Early changes in [18F]FLT uptake after chemotherapy: an experimental study. Eur J Nucl Med Mol Imaging 2002 ; 29 : 1462-9.
Gutzmer R, Guetry DT. Gene therapy for melanoma in humans. Hematol Oncol Clin N A 1998 ; 12 : 519-38.
Matthews T, Boehme R. Antiviral activity and mechanism of action of ganciclovir. Rev Infect Dis 1988 ; 10 (Suppl. 3) : S490-S494.
Ram Z, Culver KW, Oshiro EM, et al. Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nature Medicine 1997 ; 3 : 1354-61.
Yang L, Chiang Y, Lenz HJ, et al. Intercellular communication mediates the bystander effect during herpes simplex thymidine kinase/ganciclovir-based gene therapy of human gastrointestinal tumor cells. Human Gene Therapy 1998 ; 9 : 719-28.
Moolten FL, Wells JM. Curability of tumors bearing herpes thymidine kinase genes transferred by retroviral vectors. J Nat Cancer Inst 1990 ; 82 : 297-300.
Moolten FL, Wells JM, Heyman RA, et al. Lymphoma regression induced by ganciclovir in mice bearing a herpes thymidine kinase transgene. Human Gene Therapy 1990 ; 1 : 125-34.
Sterman DH, Treat J, Litzky LA, et al. Adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir gene therapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma. Human Gene Therapy 1998 ; 9 : 1083-92.
Alavi JB, Eck SL. Gene therapy for malignant gliomas. Hematol Oncol Clin N A 1998 ; 12 : 617-29.
Monclus M, Luxen A, Van Naemen J, et al. Development of PET radiopharmaceuticals for gene therapy: Synthesis of 9-((1-(18F)fluoro-3-hydroxy- 2-propoxy)methyl)guanine. J Labelled Compounds Radiopharmaceut 1995 ; 37 : 193-5.
Monclus M, Luxen A, Cool V, et al. Synthesis of (R)- and (S)-9-((3-(18 F)fluoro-1-hydroxy-2-propoxy)methyl)guanine: Radiopharmaceuticals for gene therapy. J Labelled Compounds Radiopharmaceut 1997 ; 40 : 20-2.
Habetkotn U, Khazaie K, Morr I, et al. Ganciclovir uptake in human mammary carcinoma cells expressing herpes simplex virus thymidine kinase. Nuclear Med Biol 1998 ; 25 : 367-73.
Haberkorn U, Altmann A, Morr I, et al. Monitoring gene therapy with herpes simplex virus thymidine kinase in hepatoma cells: uptake of specific substrates. J Nucl Med 1997 ; 38 : 287-94.
Hustinx R, Shiue CY, Alavi A, et al. Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-beating rodents using positron emission tomography and [18F]FHPG. Eur J Nucl Med 2001 ; 28 : 5-12.
Hospers GA, Calogero A, Van Waatde A, et al. Monitoring of herpes simplex virus thymidine kinase enzyme activity using positron emission tomography. Cancer Res 2000 ; 60 : 1488-91.
Barrio JR, Namavari M, Srinivasan A, et al. Carbon-8 radiofluorination of purines: A general approach to probe design for gene therapy in humans. J Labelled Compounds Radiopharmaceut 1997 ; 40 : 348.
Gambhir SS, Barrio JR, Wu L, et al. Imaging of adenoviral-directed herpes simplex virus type 1 thymidine kinase reporter gene expression in mice with radiolabeled ganciclovir. J Nuclear Med 1998 ; 39 : 2003-11.
Gambhir SS, Barrio JR, Phelps ME, et al. Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. Proceed Natl Acad Sci 1999 ; 96 : 2333-8.
Vere Hodge RA, Sutton D, Boyd MR, et al. Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-hydroxymethylbutyl)guanine; penciclovir]. Antimicrobial Agents Chemother 1989 ; 33 : 1765-73.
Smee DF, Boehme R, Chernow M, et al. Intracellular metabolism and enzymatic phosphorylation of 9-(1,3-dihydroxy-2-propoxymethyl)guanine and acyclovir in herpes simplex virus-infected and uninfected cells. Biochem Pharmacol 1985 ; 34 : 1049-56.
Alauddin MM, Conti PS. 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. Nuclear Med Biol 1998 ; 25 : 175-80.
Iyer M, Barrio JR, Namavari M, et al. 8-[18F]fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET. J Nucl Med 2001 ; 42 : 96-105.
Yaghoubi S, Barrio JR, Dahlbom M, 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. J Nucl Med 2001 ; 42 : 1225-34.
Tjuvajev JG, Avril N, Oku T, et al. Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. Cancer Res 1998 ; 58 : 4333-41.
Tjuvajev JG, Finn R, Watanabe K, et al. Noninvasive imaging of herpes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy. Cancer Res 1996 ; 56 : 4087-95.
Tjuvajev JG, Chen SH, Joshi A, et al. Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo. Cancer Res 1999; 59: 5186-93.
Tjuvajev JG, Stockhammet G, Desai R, et al. Imaging the expression of transfected genes in vivo. Cancer Res 1995 ; 55 : 6126-32.
Btust P, Haubner R, Friedrich A, et al. Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression. Eur J Nucl Med 2001 ; 28 : 721-9.
Tjuvajev JG, Doubrovin M, Akhurst T, et al. J Nucl Med 2002 ; 43 : 1072-83.
Pentlow KS, Gtaham MC, Lambrecht RM, et al. Quantitative imaging of iodine-124 with PET. J Nuclear Med 1996 ; 37 : 1557-62.
Ray P, Bauer E, Iyer M, et al. Monitoring gene therapy with reporter gene imaging. Semin Nucl Med 2001 ; 31 : 312-20.
Green LA, Yap CS, Nguyen K, et al. Indirect monitoring of endogenous gene expression by positron emission tomography (PET) imaging of reporter gene expression in transgenic mice. Molecular Imaging Biol 2002 ; 4 : 71-81.
Herschman HR, MacLaren DC, Iyer M, et al. Seeing is believing: non-invasive, quantitative and repetitive imaging of reporter gene expression in living animals, using positron emission tomography. J Neurosci Res 2000 ; 59 : 699-705.
Gambhir SS, Bauer E, Black ME, et al. A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography. Proceed Natl Acad Sci USA 2000 ; 97 : 2785-90.
MacLaren DC, Gambhir SS, Satyamurthy N, et al. Repetitive, non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals. Gene Therapy 1999 ; 6 : 785-91.
Yu Y, Annala AJ, Bartio JR, et al. Quantification of target gene expression by imaging reporter gene expression in living animals. Nature Med 2000 ; 6 : 933-7.
