Molecular and Clinical Imaging
In order to individualize radiation therapy, our research has focused on imaging of different biologic tumour characteristics, like glucose metabolism, hypoxia and EGFR expression. Visualization of the biological characteristics of the different parts of the tumour using different tracers could result in guidance of delivered radiation or drug doses.
A. Clinical part
Positron emission tomography (PET) scans, mainly using 18 F-fluorodeoxyglucose (FDG) as a tracer, is currently widely accepted as a diagnostic tool in oncology. PET is used to evaluated staging and to define the target volume in radiation treatment planning in order to evaluate treatment response. We focused on issues concerning the role of PET in target volume delineation, both for primary tumor and regional lymph nodes (van Baardwijk et al. 2006).
We investigated for locally advanced non–small-cell lung cancer (n=23) the changes in tumor volume, motion, and breathing frequency during a radiotherapy course using CT-PET and RC-CT scanning before and after treatment. A striking heterogeneity of tumor volume changes was observed at all time points, but no significant changes in average tumor motion or breathing frequencies were observed during treatment (fig1) (Bosmans et al. 2006). This underscores the need for repeated imaging during the course of radiotherapy. However, the changes in tumor motion are small, which indicates that RC-CT does not appear to be necessary (Nagel et al. 2006, Bosmans et al, 2006).
B. Preclinical part
Besides PET, we used also fluorescent imaging to evaluate hypoxia in solid tumors. This was done using the Salmonella bacteria, where we followed fluorescent reporter gene expression driven off a hypoxia inducible promoter. The fluorescent signals correlated well with the amount of hypoxia (Mengesha, Dubois et al. 2006).
Recently, we also investigated the binding conditions for a fluorescent labeled sulfonamide against the hypoxia surrogate marker CA IX. Both in vitro and in vivo results indicate accumulation of the sulfonamide upon hypoxia exposure, indicating the possibility of non-invasive imaging of hypoxia trough its surrogate marker CA IX
Besides imaging of hypoxia of glucose metabolism, we investigated the possibility of imaging EGFR expression using its antibody Cetuximab, which we labeled with the radio-isotope Zirconium-89. In vivo µPET studies demonstrated clear uptake in an EGFR positive tumor (fig2) and this was confirmed by histopathology.
Selected publications
Nagel, C.C., Bosmans, G., Dekker, A.L., Ollers, M.C., De Ruysscher, D.K., Lambin, P., Minken, A.W., Lang, N. and Schafers, K.P.
Phased attenuation correction in respiration correlated computed tomography/positron emitted tomography.
Med Phys, 2006, 33(6):1840-1847
van Baardwijk, A., Baumert, B. G., Bosmans, G., van Kroonenburgh, M., Stroobants, S., Gregoire, V., Lambin, P. and De Ruysscher, D.
The current status of FDG-PET in tumour volume definition in radiotherapy treatment planning.
Cancer Treat Rev, 2006, 32(4):245-260
Bosmans, G., Buijsen, J., Dekker, A., Velders, M., Boersma, L., De Ruysscher, D., Minken, A. and Lambin, P.
An "in silico" clinical trial comparing free breathing, slow and respiration correlated computed tomography in lung cancer patients.
Radiother Oncol, 2006, 81(1):73-80
Bosmans, G., van Baardwijk, A., Dekker, A., Ollers, M., Boersma, L., Minken, A., Lambin, P. and De Ruysscher, D.
Intra-patient variability of tumor volume and tumor motion during conventionally fractionated radiotherapy for locally advanced non-small-cell lung cancer: A prospective clinical study.
Int J Radiat Oncol Biol Phys, 2006, 66(3):748-753
Mengesha A., Dubois L., Lambin P., Chiu R.K., Wouters B.G., Theys J.
Targeting of attenuated Salmonella to solid tumors by using hypoxia-inducible promoter elements.
Cancer Biol Ther 5, 2006: 1120-1128
Figure 1: Tumor volumes, as determined by computed tomography (CT), relative to the volume before treatment, were plotted vs. the dose. Thick black line is the average relative CT volume together with the standard deviation. Dotted lines represents patients in whom tumors increased more than 30%; dashed lines indicate patients in whom tumors decreased 30%.
Figure 2: (a) Western Blot to validate EGFR expression of EGFR positive cell line (A431) and negative cell line (T47D).
(b) A FACS saturation experiment has been done to analyze the specific binding of the Cetuximab Oregon Green 488 probe to the EGF receptor.
(c) Micro-PET image of a nude mouse, 48 hours after injection with Zirconium- Cetuximab, with an A431 tumor in the left flank, and a T47D tumor in the right flank.
Research group
Prof.dr. Philippe Lambin, project leader
Dr. Dirk De Ruysscher
Prof.dr. Bradly Wouters
Post-doctoral fellows
Dr. Guido Lammering
Dr. Andre Dekker
PhD students
Ludwig Dubois
Geert Bosmans
Angela van Baardwijk
Hugo Aerts
Technicians
Barry Jutten
Natasja Lieuwes
Students
Roel Straathof
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