Skip to main content
SpringerLink
Log in

Monitoring of gene therapy with PET

  • Chapter
Book cover PET in Clinical Oncology

  • 150 Accesses

Abstract

The transfer and expression of suicide genes into malignant tumor cells represents an attractive approach for human gene therapy. Suicide genes typically code for non-mammalian enzymes which convert nontoxic prodrugs into highly toxic metabolites. Therefore, systemic application of the nontoxic prodrug results in the production of the active drug at the tumor site. Although a broad range of suicide principles has been described, two suicide systems are applied in most studies: the cytosine deaminase (CD) and herpes simplex virus thymidine kinase (HSV-tk).

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 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alauddin MM, Conti PS (1998) 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. Nucl Med Biol 25:175–180

    Article  PubMed  CAS  Google Scholar 

  2. Alauddin MM, Shahinian A, Kundu RK, Gordon EM, Conti PS (1999) Evaluation of 9-[(3–18F-fluoro-l-hydroxy-2-propoxy)methyl]guanine ([18F]-FHPG) in vitro and in vivo as a probe for PET imaging of gene incorporation and expression in tumors. Nucl Med Biol 26:371–376

    Article  PubMed  CAS  Google Scholar 

  3. Barba D, Hardin J, Sadelain M, Gage FH (1994) Development of anti-tumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc Natl Acad Sci USA 91:4348–4352

    Article  PubMed  CAS  Google Scholar 

  4. Bergstrom M, Muhr C, Lundberg PO, Bergstrom K, Gee AD, Fasth KJ, Langstrom B (1987) Rapid decrease in amino acid metabolism in prolactin-secreting pituitary adenomas after bromocriptine treatment: a PET study. J Comput Assist Tomogr 11:815–819

    Article  PubMed  CAS  Google Scholar 

  5. Bogdanov A, Petherick P, Marecos E, Weissleder R (1997) In vivo localization of diglycylcysteine-bearing synthetic peptides by nuclear imaging of oxotechnetate transchelation. Nucl Med Biol 24:739–742

    Article  PubMed  CAS  Google Scholar 

  6. Bogdanov A, Simonova M, Weissleder R (1998) Design of metal-binding green fluorescent plotein variants. Biochim Biophys Acta 1397:56–64

    Article  PubMed  CAS  Google Scholar 

  7. Borrelli E, Heyman R, Hsi M, Evans RM (1988) Targeting of an inducible toxic phenotype in animal cells. Proc Natl Acad Sci USA 85:7572–7576

    Article  PubMed  CAS  Google Scholar 

  8. Caruso M, Panis Y, Gagandeep S, Houssin D, Salzmann JL, Klatzman D (1993) Regression of established macroscopic liver metastases after in situ transduction of a suicide gene. Proc Natl Acad Sci USA 90:7024–7028

    Article  PubMed  CAS  Google Scholar 

  9. Chen SH, Shine HD, Goodman JC, Grossman RG, Woo SLC (1994) Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo. Proc Natl Acad Sci USA 91:3054–3057

    Article  PubMed  CAS  Google Scholar 

  10. Christman D, Crawford EJ, Friedkin M, Wolf AP (1972) Detection of DNA synthesis in intact organisms with positron-emitting (methyl-11C)thymidine. Proc Natl Acad Sci USA 69:988–992

    Article  PubMed  CAS  Google Scholar 

  11. Clancy BM, Czech MP (1990) Hexose transport stimulation and membrane redistribution of glucose transporter isoforms in response to cholera toxin, dibutyryl cyclic AMP, and insulin in 3T3 adipocytes. J Biol Chem 265:12434–12443

    PubMed  CAS  Google Scholar 

  12. Culver KW, Ram Z, Walbridge S et al. (1992) In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 256:1550–1552

    Article  PubMed  CAS  Google Scholar 

  13. Gambhir SS, Barrio JR, Phelps ME, Iyer M, Namavari M, Satyamurthy N, Wu L, Green LA, Bauer E, MacLaren DC, Nguyen K, Berk AJ, Cherry SR, Herschman HR (1999) Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography. Proc Natl Acad Sci USA 96:2333–2338

    Article  PubMed  CAS  Google Scholar 

  14. Gati WP, Misra HK, Knaus EE, Wiebe LI (1984) Structural modifications at the 2’ and 3’ positions of some pyrimidine nucleosides as determinants of their interaction with the mouse erythrocyte nucleoside transporter. Biochem Pharmacol 33:3325–3331

    Article  PubMed  CAS  Google Scholar 

  15. Haberkorn U (1999) Monitoring of gene transfer for cancer therapy with radioactive isotopes. Ann Nucl Med 13:369–377

    Article  PubMed  CAS  Google Scholar 

  16. Haberkorn U, Altmann A, Morr I et al. (1997) Gene therapy with herpes simplex virus thymidine kinase in hepatoma cells: uptake of specific substrates. J Nucl Med 38:287–294

    PubMed  CAS  Google Scholar 

  17. Haberkorn U, Altmann A, Morr I, Germann C, Oberdorfer F, Kaick G van (1997) Multi tracer studies during gene therapy of hepatoma cells with HSV thymidine kinase and ganciclovir. J Nucl Med 38:1048–1054

    PubMed  CAS  Google Scholar 

  18. Haberkorn U, Bellemann ME, Altmann A, Gerlach L, Morr I, Oberdorfer F, Brix G, Doll J, Blatter J, Kaick G van (1997) F-18-fluoro-2-deoxyglucose uptake in rat prostate adenocarcinoma during chemotherapy with 2’,2’-difluoro-2’-deoxycytidine. J Nucl Med 38:1215–1221

    PubMed  CAS  Google Scholar 

  19. Haberkorn U, Bellemann ME, Gerlach L, Morr I, Trojan H, Brix G, Altmann A, Doll J, Kaick G van (1998) Uncoupling of 2-fluoro-2-deoxyglucose transport and phosphorylation in rat hepatoma during gene therapy with HSV thymidine kinase. Gene Ther 5:880–887

    Article  PubMed  CAS  Google Scholar 

  20. Haberkorn U, Khazaie K, Morr I, Altmann A, Müller M, Kaick G van (1998) Ganciclovir uptake in human mammary carcinoma cells expressing Herpes Simplex Virus thymidine kinase. Nucl Med Biol 25:367–373

    Article  PubMed  CAS  Google Scholar 

  21. Haberkorn U, Morr I, Oberdorfer F et al. (1994) Fluorodeoxyglucose uptake in vitro: aspects of method and effects of treatment with gemcitabine. J Nucl Med 35:1842–1850

    PubMed  CAS  Google Scholar 

  22. Haberkorn U, Oberdorfer F, Klenner T et al. (1994) Metabolic and transcriptional changes in osteosarcoma cells treated with chemotherapeutic drugs. Nucl Med Biol 21:835–845

    Article  PubMed  CAS  Google Scholar 

  23. Haberkorn U, Oberdorfer F, Gebert J et al. (1996) Monitoring of gene therapy with cytosine deaminase: in vitro studies using 3H-5-fluorocytosine. J Nucl Med 37:87–94

    PubMed  CAS  Google Scholar 

  24. Haberkorn U, Reinhardt M, Strauss LG et al. (1992) Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy. J Nucl Med 33:1981–1987

    PubMed  CAS  Google Scholar 

  25. Haberkorn U, Strauss LG, Dimitrakopoulou A et al. (1993) Fluorodeoxyglucose imaging of advanced head and neck cancer after chemotherapy. J Nucl Med 34:12–17

    PubMed  CAS  Google Scholar 

  26. Huber BE, Austin EA, Good SS, Knick VC, Tibbels S, Richards CA (1993) In vivo antitumor activity of 5-fluorocytosine on human colorectal carcinoma cells genetically modified to express cytosine deaminase. Cancer Res 53:4619–4626

    PubMed  CAS  Google Scholar 

  27. Izquierdo M et al. (1995) Long-term rat survival after malignant brain tumour regression by retroviral gene therapy. Gene Ther 2:66–69

    PubMed  CAS  Google Scholar 

  28. Keller PM, Fyfe JA, Beauchamp L et al. (1981) Enzymatic phosphorylation of acyclic nucleoside analogs and correlations with antiherpetic activities. Biochem Pharmacol 30:3071–3077

    Article  PubMed  CAS  Google Scholar 

  29. Koechlin BA, Rubio F, Palmer S, Gabriel T, Duschinsky R (1966) The metabolism of 5-fluorocytosine-2-14C and of cytosine-1-14C in the rat and the disposition of 5-fluorocytosine-2-14C in man. Biochem Pharmac 15:435–446

    Article  CAS  Google Scholar 

  30. MacLaren DC, Gambhir SS, Satyamurthy N et al. (1999) Repetitive non-invasive imaging of the dopamine D2 receptor as a reporter gene in living animals. Gene Ther 6:785–791

    Article  PubMed  CAS  Google Scholar 

  31. Mahony WB, Domin BA, McConnel RT, Zimmerman TP (1988) Acyclovir transport into human erythrocytes. J Biol Chem 263:9285–9291

    PubMed  CAS  Google Scholar 

  32. Mandell RB, Mandell LZ, Link CJ Jr (1999) Radioisotope concentrator gene therapy using the sodium/iodide symporter gene. Cancer Res 59:661–668

    PubMed  CAS  Google Scholar 

  33. Maron A et al. (1996) Gene therapy of rat C6 glioma using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene: long-term follow up by magnetic resonance imaging. Gene Ther 3:315–322

    PubMed  CAS  Google Scholar 

  34. Morin KW, Knaus EE, Wiebe LI (1997) Non-invasive scintigraphic monitoring of gene expression in a HSV-1 thymidine kinase gene therapy model. Nucl Med Cornmun 18:599–605

    Article  CAS  Google Scholar 

  35. Monclus M, Luxen A, Van Naemen J et al. (1995) Development of PET radiopharmaceuticals for gene therapy: synthesis of 9-((1-(18F)fluoro-3-hydroxy-2-propoxy)methyl)guanine. J Label Comp Radiopharm 37:193–195

    Google Scholar 

  36. Moolten FL, Wells JM (1990) Curability of tumors bearing Herpes thymidine kinase genes transferred by retroviral vectors. J Natl Cancer Inst 82:297–300

    Article  PubMed  CAS  Google Scholar 

  37. Mullen CA, Coale MM, Lowe R, Blaese RM (1994) Tumors expressing the cytosine deaminase suicide gene can be eliminated in vivo with 5-fluorocytosine and induce protective immunity to wild type tumor. Cancer Res 54:1503–1506

    PubMed  CAS  Google Scholar 

  38. Mullen CA, Kilstrup M, Blaese M (1992) Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system. Proc Natl Acad Sci USA 89:33–37

    Article  PubMed  CAS  Google Scholar 

  39. Myers CE (1981) The pharmacology of the fluoropyrimidines. Pharmacological Reviews 33:1–15

    PubMed  CAS  Google Scholar 

  40. Nishiyama T, Kawamura Y, Kawamoto K, Matsumura H, Yamamoto N, Ito T, Ohyama A, Katsuragi T, Sakai T (1985) Antineoplastic effects of 5-fluorocytosine in combination with cytosine deaminase capsules. Cancer Res 45:1753–1761

    PubMed  CAS  Google Scholar 

  41. Oldfield EH, Ram Z, Culver KW, Blaese RM, DeVroom HL, Anderson WF (1993) Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir. Hum Gene Ther 1:39–69

    Article  Google Scholar 

  42. Pasternak CA, Aiyathurai JEJ, Makinde V et al. (1991) Regulation of glucose uptake by stressed cells. J Cell Physiol 149:324–331

    Article  PubMed  CAS  Google Scholar 

  43. Polak A, Eschenhof E, Fernex M, Scholer HJ (1976) Metabolic studies with 5-fluorocytosine-6-14C in mouse, rat, rabbit, dog and man. Chemotherapy 22:137–153

    Article  PubMed  CAS  Google Scholar 

  44. Price R, Cardle K, Watanabe K (1983) The use of antiviral drugs to image herpes encephalitis. Cancer Res 43:3619–3627

    Google Scholar 

  45. Ram Z, Culver WK, Walbridge S et al. (1993) In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res 53:83–88

    PubMed  CAS  Google Scholar 

  46. Rozenthal JM, Levine RL, Nickles RJ, Dobkin JA (1989) Glucose uptake by gliomas after treatment. Arch Neurol 46:1302–1307

    Article  Google Scholar 

  47. Saito Y, Price R, Rottenberg DA, Fox JJ, Su TL, Watanabe KA, Philipps FA (1982) Quantitative autoradiographic mapping of herpes simplex virus encephalitis with radiolabeled antiviral drug. Science 217:1151–1153

    Article  PubMed  CAS  Google Scholar 

  48. Scholer HJ (1980) Flucytosine. In: Speller DCE (ed) Antifungal Chemotherapy. John Wiley & Sons, Chichester New York, pp 35–106

    Google Scholar 

  49. Shields AF et al. (1990) Utilization of labeled thymidine in DNA synthesis: studies for PET. J Nucl Med 31:337–342

    PubMed  CAS  Google Scholar 

  50. Shields AF, Grierson JR, Dohmen BM et al. (1998) Imaging proliferation in vivo with (F-18)FLT and positron emission tomography. Nature Med 4:1334–1336

    Article  PubMed  CAS  Google Scholar 

  51. Sobol RE et al. (1995) Interleukin-2 gene therapy in a patient with glioblastoma. Gene Ther 2:164–167

    PubMed  CAS  Google Scholar 

  52. Tjuvajev JG, Avril N, Oku T et al. (1998) Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography. Cancer Res 58:4333–4341

    CAS  Google Scholar 

  53. Tjuvajev JG, Stockhammer G, Desai R, Uehara H, Watanabe K, Gansbacher B, Blasberg RG (1995) Imaging the expression of transfected genes in vivo. Cancer Res 55:6126–6132

    PubMed  CAS  Google Scholar 

  54. Visser GWM, Boele S, Knops GHJN, Herscheid JDM, Hoekstra A (1985) Synthesis and biodistribution of (18F)-5-fluorocytosine. Nucl Med Comm 6:455–459

    Article  CAS  Google Scholar 

  55. Wahl RL et al. (1993) Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: initial evaluation. J Clin Oncol 11:2101–2111

    PubMed  CAS  Google Scholar 

  56. Wallace PM, MacMaster JF, Smith VF, Kerr DE, Senter PD, Cosand WL (1994) Intratumoral generation of 5-fluorouracil mediated by an antibody-cytosine deaminase conjugate in combination with 5-fluorocytosine. Cancer Res 54:2719–2723

    PubMed  CAS  Google Scholar 

  57. Wertheimer E, Sasson S, Cerasi E, Ben-Neriah Y (1991) The ubiquitous glucose transporter GLUT-1 belongs to the glucose-regulated protein family of stress-inducible proteins. Proc Natl Acad Sci USA 88:2525–2529

    Article  PubMed  CAS  Google Scholar 

  58. Weissleder R, Simonova M, Bogdanova A et al. (1997) MR imaging and scintigraphy of gene expression through melanin induction. Radiology 204:425–429

    PubMed  CAS  Google Scholar 

  59. Widnell CC, Baldwin SA, Davies A, Martin S, Pasternak CA (1990) Cellular stress induces a redistribution of the glucose transporter. FASEB J 4:1634–1637

    PubMed  CAS  Google Scholar 

  60. Wiebe LI, Morin KW, Knaus EE (1997) Radiopharmaceuticals to monitor gene transfer. Q J Nucl Med 41:79–89

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. U. Haberkorn
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Bundeswehrzentralkrankenhaus Koblenz, Abteilung XV - Nuklearmedizin, Rübenacher Straße 170, Koblenz, 56072, Germany

    H. J. Wieler

  2. Division of Nuclear Medicine, Department of Radiology, DUMC 3949, Room 1419, Duke North Erwin Road, Durham, NC, 27710, USA

    R. Edward Coleman M.D. (Professor of Radiology, Vice-Chairman, Director) (Professor of Radiology, Vice-Chairman, Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Haberkorn, U. (2000). Monitoring of gene therapy with PET. In: Wieler, H.J., Coleman, R.E. (eds) PET in Clinical Oncology. Steinkopff, Heidelberg. https://doi.org/10.1007/978-3-642-57703-1_31

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-57703-1_31

  • Publisher Name: Steinkopff, Heidelberg

  • Print ISBN: 978-3-642-63329-4

  • Online ISBN: 978-3-642-57703-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation