Non-invasive detection of tumor hypoxia by DCE-MRI

1. Research group name/project:
Non-invasive detection of tumor hypoxia by DCE-MRI

2. Group leader and some key members (incl. from other depts./inst.):
Einar K. Rofstad (prof.), Kjetil G. Brurberg (Post-doc), Ilana C. Benjaminsen (Post-doc), Jon-Vidar Gaustad (Ph.D. stud.), Tormod A.M. Egeland (Ph.D. stud.), Kristine Gulliksrud (Ph.D. stud.), Trude G. Simonsen (Ph.D. stud.), Christine Ellingsen (Ph.D. stud.), Camilla Mollatt (techn.), Berit Mathiesen (techn.), Kanthi Galappathi (techn.)


3. Home address on the internet:
http://radium.no/rofstad

4. Department/Institute:
Department of Biophysics, Institute for Cancer Research

4b. Hospital (HF):
Det norske radiumhospital HF

5. Main aim of research group:
Tumor hypoxia is the primary cause of radiation resistance in several histological types of cancer. The main aim of the project is to develop a non-invasive method for detection of hypoxic regions within tumors. Our hypothesis is that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may be a useful method.

6. Some important recent results (with a few key references):
Tumors have inadequate blood supply and show elevated respiratory activity, which may lead to significant intra- and intertumor heterogeneity in chronic (Rofstad and Måseide, Int. J. Radiat. Biol. 75:1377-1393, 1999) and acute (Brurberg et al, Br. J. Cancer 89:350-356, 2003; Brurberg et al, Int. J. Radiat. Oncol. Biol. Phys, in press, 2004) hypoxia. DCE-MRI may provide detailed information about the blood supply in tumors at the regional level (Lyng et al, Int. J. Cancer, 96:182-190, 2001). Moreover, high-resolution perfusion images may be obtained by DCE-MRI (Benjaminsen et al, Magn. Reson. Med., submitted, 2004). Data suggesting that DCE-MRI may provide useful images of tumor cell density and hence tumor respiratory activity have also been established. Future plans include comparative studies of tumor contrast enhancement measured by DCE-MRI, tumor pO2 distributions measured with pO2 electrodes, and the distribution of tumor hypoxia measured immunohistochemically by using pimonidazole as a hypoxia marker.

7. Methods in current use:
Amelanotic human melanomas xenografted into BALB/c-nu/nu mice are used as preclinical models of human cancer. Clinical studies are performed in canine tumors and human cervix carcinomas. DCE-MRI is performed at 1.5 T by using a clinical MR-tomograph. Gd-DTPA is used as contrast agent. Oxygen tension is measured by using oxygen electrodes and hypoxia markers (pimonidazole).

8. Available equipment:
Eppendorf and Oxylite oxygen electrode systems. Clinical 1.5 T MR-tomograph (General Electric).

9. Collaborators:
9.1. Among Helse Sør hospitals : Department of Radiology and Department of Medical Physics, The Norwegian Radium Hospital.

10. Is the group interested in joining a larger collaborative project in Helse Sør:
Yes

11. Tentative name of possible collaborative project(s):
Intensity-modulated radiation therapy (IMRT) guided by hypoxia imaging.

12. Some key search words:
DCE-MRI, radiation therapy, hypoxia, oxygen tension, tumor blood perfusion.