Skip to main content
SpringerLink
Log in

Preclinical MRI Experience in Imaging Angiogenesis

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Magnetic resonance imaging (MRI) provides a range of non-invasive measures for visualization of tumor angiogenesis in the clinic as well as in experimental tumor models. MRI methods were developed for assessment of spatial and temporal changes in perfusion, blood volume fraction, vascular permeability, vascular function, vascular maturation, vessel diameter and tortuosity. Molecular targeted contrast agents were used for mapping specific markers of neovasculature. These approaches were applied for analysis of a number of regulatory mechanisms controlling tumor angiogenesis and for preclinical evaluation of tumor response to antiangiogenic agents.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Folkman J, D'Amore PA: Blood vessel formation: what is its molecular basis? Cell 87: 1153-1155, 1996

    Google Scholar 

  2. Folkman J: New perspectives in clinical oncology from angiogenesis research. Eur J Cancer 32A: 2534-2539, 1996

    Google Scholar 

  3. D'Amore PA, Shima DT: Tumor angiogenesis: a physiological process or genetically determined? Cancer Metastasis Rev 15: 205-212, 1996

    Google Scholar 

  4. Streichhan P, Fischer M, Acker H: The behaviour of the tissue pO2 in transparent chambers of rats with and without tumour implantations. Adv Exp Med Biol 191: 785-794, 1985

    Google Scholar 

  5. Ogawa S, Lee TM, Nayak AS, Glynn P: Oxygenationsensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Magn Reson Med 14: 68-78, 1990

    Google Scholar 

  6. Detre JA, Leigh JS, Williams DS, Koretsky AP: Perfusion imaging. Magn Reson Med 23: 37-45, 1992

    Google Scholar 

  7. Detre JA, Zhang W, Roberts DA, Silva AC, Williams DS, Grandis DJ, Koretsky AP, Leigh JS: Tissue specific perfusion imaging using arterial spin labeling. NMR Biomed 7: 75-82, 1994

    Google Scholar 

  8. Abramovitch R, Meir G, Neeman M: Neovascularization induced growth of implanted C6 glioma multicellular spheroids: magnetic resonance microimaging. Cancer Res 55: 1956-1962, 1995

    Google Scholar 

  9. Abramovitch R, Frenkiel D, Neeman M: Analysis of subcutaneous angiogenesis by gradient echo magnetic resonance imaging. Magn Reson Med 39: 813-824, 1998

    Google Scholar 

  10. Griffiths JR, Taylor NJ, Howe FA, Saunders MI, Robinson SP, Hoskin PJ, Powell ME, Thoumine M, Caine LA, Baddeley H: The response of human tumors to carbogen breathing, monitored by gradient-recalled echo magnetic resonance imaging. Int J Radiat Oncol Biol Phys 39: 697-701, 1997

    Google Scholar 

  11. Abramovitch R, Dafni H, Smouha E, Benjamin LE, Neeman M: In vivo prediction of vascular susceptibility to vascular endothelial growth factor withdrawal: magnetic resonance imaging of C6 rat glioma in nude mice. Cancer Res 59: 5012-5016, 1999

    Google Scholar 

  12. Tempel C, Neeman M: Spatial and temporal modulation of perfusion in the rat ovary measured by arterial spin labeling MRI. J Magn Reson Imaging 9: 794-803, 1999

    Google Scholar 

  13. Tempel C, Neeman M: Perfusion of the rat ovary: application of pulsed arterial spin labeling MRI. Magn Reson Med 41: 113-123, 1999

    Google Scholar 

  14. Hawighorst H, Knapstein PG, Weikel W, Knopp MV, Zuna I, Knof A, Brix G, Schaeffer U, Wilkens C, Schoenberg SO, Essig M, Vaupel P, van Kaick G: Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement. Cancer Res 57: 4777-4786, 1997

    Google Scholar 

  15. Tofts PS, Brix G, Buckley DL, Evelhoch JL, Henderson E, Knopp MV, Larsson HB, Lee TY, Mayr NA, Parker GJ, Port RE, Taylor J, Weisskoff RM: Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging 10: 223-232, 1999

    Google Scholar 

  16. Taylor JS, Tofts PS, Port R, Evelhoch JL, Knopp M, Reddick WE, Runge VM, Mayr N: MR imaging of tumor microcirculation: promise for the new millenium. J Magn Reson Imaging 10: 903-907, 1999

    Google Scholar 

  17. Brasch R, Pham C, Shames D, Roberts T, van Dijke K, van Bruggen N, Mann J, Ostrowitzki S, Melnyk O: Assessing tumor angiogenesis using macromolecular MR imaging contrast media. J Magn Reson Imaging 7: 68-74, 1997

    Google Scholar 

  18. Bhujwalla ZM, Artemov D, Glockner J: Tumor angiogenesis, vascularization, and contrast-enhanced magnetic resonance imaging. Top Magn Reson Imaging 10: 92-103, 1999

    Google Scholar 

  19. Gillies RJ, Bhujwalla ZM, Evelhoch JL, Garwood M, Neeman M, Robinson SP, Ronen SM, Sotak CH, van der Sanden B: Applications of magnetic resonance in model systems I: tumor biology and physiology. Neoplasia 2: 139-151, 2000

    Google Scholar 

  20. Dennie J, Mandeville JB, Boxerman JL, Packard SD, Rosen BR, Weisskoff RM: NMRimaging of changes in vascular morphology due to tumor angiogenesis, Magn Reson Med 40: 793-799, 1998

    Google Scholar 

  21. Kassner A, Annesley DJ, Zhu XP, Li KL, Kamaly-Asl ID, Watson Y, Jackson A: Abnormalities of the contrast re-circulation phase in cerebral tumors demonstrated using dynamic susceptibility contrast-enhanced imaging: a possible marker of vascular tortuosity. J Magn Reson Imaging 11: 103-113, 2000

    Google Scholar 

  22. Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KC: Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging. Nat Med 4: 623-626, 1998

    Google Scholar 

  23. Kunz-Schughart LA: Multicellular tumor spheroids: intermediates between monolayer culture and in vivo tumor, Cell Biol Int 23: 157-161, 1999

    Google Scholar 

  24. Mueller-Klieser W: Three-dimensional cell cultures: from molecular mechanisms to clinical applications. Am J Physiol 273: C1109-C1123, 1997

    Google Scholar 

  25. Shweiki D, Neeman M, Itin A, Keshet E: Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. Proc Natl Acad Sci USA 92: 768-772, 1995

    Google Scholar 

  26. Furman-Haran E, Margalit R, Grobgeld D, Degani H: Dynamic contrast-enhanced magnetic resonance imaging reveals stress-induced angiogenesis in MCF7 human breast tumors. Proc Natl Acad Sci USA 93: 6247-6251, 1996

    Google Scholar 

  27. Carmeliet P, Dor Y, Herbert J-M, Fukumara D, Brusselmans K, Dewerchin M, Neeman M, Bono F, Abramovitch R, Maxwell P, Koch CJ, Ratcliffe P, Moons L, Jain RK, Collen D, Keshet E: Role of HIF-1a in hypoxiamediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394: 485, 1998

    Google Scholar 

  28. Ravi R, Mookerjee B, Bhujwalla ZM, Sutter CH, Artemov D, Zeng Q, Dillehay LE, Madan A, Semenza GL, Bedi A: Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha. Genes Dev 14: 34-44, 2000

    Google Scholar 

  29. Benjamin LE, Keshet E: Conditional switching of vascular endothelial growth factor (VEGF) expression in tumors: induction of endothelial cell shedding and regression of hemangioblastoma-like vessels by VEGF withdrawal. Proc Natl Acad Sci USA 94: 8761-8766, 1997

    Google Scholar 

  30. Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E: Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 103: 159-165, 1998

    Google Scholar 

  31. Abramovitch R, Marikovsky M, Meir G, Neeman M: Stimulation of tumour angiogenesis by proximal wounds: spatial and temporal analysis by MRI. Br J Cancer 77: 440-447, 1998

    Google Scholar 

  32. Abramovitch R, Marikovsky M, Meir G, Neeman M: Stimulation of tumour growth by wound-derived growth factors. Br J Cancer 79: 1392-1398, 1999

    Google Scholar 

  33. Abramovitch R, Neeman M, Reich R, Stein I, Keshet E, Abraham J, Solomon A, Marikovsky M: Intercellular communication between vascular smooth muscle and endothelial cells mediated by heparin-binding epidermal growth factor-like growth factor and vascular endothelial growth factor. FEBS Lett 425: 441-447, 1998

    Google Scholar 

  34. Furman-Haran E, Grobgeld D, Margalit R, Degani H: Response of MCF7 human breast cancer to tamoxifen: evaluation by the three-time-point, contrast-enhanced magnetic resonance imaging method. Clin Cancer Res 4: 2299-2304, 1998

    Google Scholar 

  35. Furman-Haran E, Margalit R, Maretzek AF, Degani H: Angiogenic response of MCF7 human breast cancer to hormonal treatment: assessment by dynamic GdDTPAenhanced MRI at high spatial resolution. J Magn Reson Imaging 6: 195-202, 1996

    Google Scholar 

  36. Schiffenbauer YS, Abramovitch R, Meir G, Nevo N, Holzinger M, Itin A, Keshet E, Neeman M: Loss of ovarian function promotes angiogenesis in human ovarian carcinoma. Proc Natl Acad Sci USA 94: 13 203-13 208, 1997

    Google Scholar 

  37. Gilead A, Neeman M: Dynamic remodeling of the vascular bed precedes tumor growth: MLS ovarian carcinoma spheroids implanted in nude mice. Neoplasia 1: 226-230, 1999

    Google Scholar 

  38. Beauregard DA, Thelwall PE, Chaplin DJ, Hill SA, Adams GE, Brindle KM: Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status. Br J Cancer 77: 1761-1767, 1998

    Google Scholar 

  39. Pham CD, Roberts TP, van Bruggen N, Melnyk O, Mann J, Ferrara N, Cohen RL, Brasch RC: Magnetic resonance imaging detects suppression of tumor vascular permeability after administration of antibody to vascular endothelial growth factor. Cancer Invest 16: 225-230, 1998

    Google Scholar 

  40. Bogdanov AJ, Marecos E, Cheng HC, Chandrasekaran L, Krutzsch HC, Roberts DD, Weissleder R: Treatment of experimental brain tumors with trombospondin-1 derived peptides: an in vivo imaging study. Neoplasia 1: 438-445, 1999

    Google Scholar 

  41. Abramovitch R, Dafni H, Neeman M, Nagler A, Pines M: Inhibition of neovascularization and tumor growth, and facilitation of wound repair, by halofuginone, an inhibitor of collagen type I synthesis. Neoplasia 1: 321-329, 1999

    Google Scholar 

  42. Gross DJ, Reibstein I, Weiss L, Slavin S, Stein I, Neeman M, Abramovitch R, Benjamin LE: The antiangiogenic agent linomide inhibits the growth rate of von Hippel-Lindau paraganglioma xenografts to mice. Clin Cancer Res 5: 3669-3675, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel

    Michal Neeman

Authors
  1. Michal Neeman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Neeman, M. Preclinical MRI Experience in Imaging Angiogenesis. Cancer Metastasis Rev 19, 39–43 (2000). https://doi.org/10.1023/A:1026583911941

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026583911941

Search

Navigation