PURPOSE: Angiogenesis is a key event in the progression of glioblastomas (GBM). Our goal was to measure different anatomical and physiological parameters of GBM vessels using steady-state contrast-enhanced magnetic resonance imaging (SSCE-MRI), together with the assessment of biochemical parameters on GBM proliferation and angiogenesis using [(11)C]methyl-L-methionine (MET) and 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) and positron emission tomography (PET). We focused on how these anatomical and biochemical read-outs correlate with one another and with immunohistochemistry. METHODS: SSCE-MRI together with (11)C-MET and (18)F-FLT PET were performed 3 weeks after intracranial implantation of human GBM spheroids in nude rats (n = 8). Total cerebral blood volume (tCBV), blood volume present in microvessels (μCBV), vessel density and size were calculated. Rats were treated with bevacizumab (n = 4) or vehicle (n = 4) for 3 weeks. Imaging was repeated at week 6, and thereafter immunohistochemistry was performed. RESULTS: Three weeks after implantation, MRI showed an increase of vessel density and μCBV in the tumour compared to the contralateral brain. At week 6, non-treated rats showed a pronounced increase of (11)C-MET and (18)F-FLT tumour uptake. Between weeks 3 and 6, tCBV and vessel size increased, whereas vessel density and μCBV decreased. In rats treated with bevacizumab μCBV values were significantly smaller at week 6 than in non-treated rats, whereas the mean vessel size was higher. Accumulation of both radiotracers was lower for the treated versus the non-treated group. Most importantly, non-invasive measurement of tumour vessel characteristics and tumour proliferation correlated to immunohistochemistry findings. CONCLUSION: Our study demonstrates that SSCE-MRI enables non-invasive assessment of the anatomy and physiology of the vasculature of experimental gliomas. Combined SSCE-MRI and (11)C-MET/(18)F-FLT PET for monitoring biochemical markers of angiogenesis and proliferation in addition to vessel anatomy could be useful to improve our understanding of therapy response of gliomas.
PURPOSE: Angiogenesis is a key event in the progression of glioblastomas (GBM). Our goal was to measure different anatomical and physiological parameters of GBM vessels using steady-state contrast-enhanced magnetic resonance imaging (SSCE-MRI), together with the assessment of biochemical parameters on GBM proliferation and angiogenesis using [(11)C]methyl-L-methionine (MET) and 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) and positron emission tomography (PET). We focused on how these anatomical and biochemical read-outs correlate with one another and with immunohistochemistry. METHODS: SSCE-MRI together with (11)C-MET and (18)F-FLT PET were performed 3 weeks after intracranial implantation of human GBM spheroids in nude rats (n = 8). Total cerebral blood volume (tCBV), blood volume present in microvessels (μCBV), vessel density and size were calculated. Rats were treated with bevacizumab (n = 4) or vehicle (n = 4) for 3 weeks. Imaging was repeated at week 6, and thereafter immunohistochemistry was performed. RESULTS: Three weeks after implantation, MRI showed an increase of vessel density and μCBV in the tumour compared to the contralateral brain. At week 6, non-treated rats showed a pronounced increase of (11)C-MET and (18)F-FLTtumour uptake. Between weeks 3 and 6, tCBV and vessel size increased, whereas vessel density and μCBV decreased. In rats treated with bevacizumab μCBV values were significantly smaller at week 6 than in non-treated rats, whereas the mean vessel size was higher. Accumulation of both radiotracers was lower for the treated versus the non-treated group. Most importantly, non-invasive measurement of tumour vessel characteristics and tumour proliferation correlated to immunohistochemistry findings. CONCLUSION: Our study demonstrates that SSCE-MRI enables non-invasive assessment of the anatomy and physiology of the vasculature of experimental gliomas. Combined SSCE-MRI and (11)C-MET/(18)F-FLT PET for monitoring biochemical markers of angiogenesis and proliferation in addition to vessel anatomy could be useful to improve our understanding of therapy response of gliomas.
Authors: Thomas Viel; Krishna M Talasila; Parisa Monfared; Jian Wang; Jan F Jikeli; Yannic Waerzeggers; Bernd Neumaier; Heiko Backes; Narve Brekka; Frits Thorsen; Daniel Stieber; Simone P Niclou; Alexandra Winkeler; Bertrand Tavitian; Mathias Hoehn; Rolf Bjerkvig; Hrvoje Miletic; Andreas H Jacobs Journal: J Nucl Med Date: 2012-06-11 Impact factor: 10.057
Authors: Frederic G Dhermain; Peter Hau; Heinrich Lanfermann; Andreas H Jacobs; Martin J van den Bent Journal: Lancet Neurol Date: 2010-08-10 Impact factor: 44.182
Authors: Joachim Drevs; Ralph Müller-Driver; Christine Wittig; Stefan Fuxius; Norbert Esser; Harald Hugenschmidt; Moritz A Konerding; Peter R Allegrini; Jeanette Wood; Jürgen Hennig; Clemens Unger; Dieter Marmé Journal: Cancer Res Date: 2002-07-15 Impact factor: 12.701
Authors: P S Tofts; G Brix; D L Buckley; J L Evelhoch; E Henderson; M V Knopp; H B Larsson; T Y Lee; N A Mayr; G J Parker; R E Port; J Taylor; R M Weisskoff Journal: J Magn Reson Imaging Date: 1999-09 Impact factor: 4.813
Authors: Kyrre E Emblem; Christian T Farrar; Elizabeth R Gerstner; Tracy T Batchelor; Ronald J H Borra; Bruce R Rosen; A Gregory Sorensen; Rakesh K Jain Journal: Nat Rev Clin Oncol Date: 2014-08-12 Impact factor: 66.675
Authors: Philip J O'Halloran; Thomas Viel; David W Murray; Lydia Wachsmuth; Katrin Schwegmann; Stefan Wagner; Klaus Kopka; Monika A Jarzabek; Patrick Dicker; Sven Hermann; Cornelius Faber; Tim Klasen; Michael Schäfers; David O'Brien; Jochen H M Prehn; Andreas H Jacobs; Annette T Byrne Journal: Eur J Nucl Med Mol Imaging Date: 2016-03-15 Impact factor: 9.236