Fusion of PET and Molecular Biology
Dynamic PET data reflect accurately molecular biological processes. For the a correlative analysis of PET and gene expression data two data sets are needed:
1. Dynamic PET data from a target volume, analysed using appropriate compartment and/or non-compartment models
2. Gene expression data, obtained from the same volume analysed by PET.
Our Approach
Several studies are performed in oncological patients undergoing surgery within two days after PET. Generally a dynamic PET examination is performed in all patients, focussed on the region of the primary tumor. Following PET, a quantitative analysis is performed, including the calculation of the SUV and compartment and non-compartment modeling. Thus, about 7 parameters is obtained, e.g. for a F-18-Deoxyglucose (FDG) study, which contain the major information about the tracer characteristics in a target volume. This procedure is peformed for the tumor volume prior to surgery and a reference area, which is usually analysed following surgery, based on the information obtained from the surgeon about the location where the specimen was removed. We use a dedicated software for the quantitative assessment of dynamic PET studies.
Following PET, a tissue specimen is removed during the surgery from the area where the PET data were obtained. Furthermore, also a specimen from a reference area is obtained, which is spatially correlated with the corresponding PET area. We use commercially available gene arrays (e.g. U133A, Affymetrix Inc.) for the quantitative assessment of gene expression. The expression data were normalised and combined with the corresponding PET data for further data analysis.
A dedicated software was developed from our group for the correlative assessment of PET and gene array data, named GenePET. Our primary interest was focussed on the glucose transporters and hexokinases, but also on genes related to angiogenesis, proliferation, and hypoxia. Methodological aspects of the GenePET software and results in patients with giant cell tumors and primary colorectal tumors are already published. The results demonstrate, that the FDG kinetics is modulated e.g. by genes associated with angiogenesis. Furthermore, for dedicated tumors it is possible to predict the expression of VEGF-A and angiopoietin-2 from the dynamic PET data. Thus, it seems to be possible to calculate an individual risk index for these patients, based on PET data.
Strauss LG, Dimitrakopoulou-Strauss A, Koczan D, Bernd L, Haberkorn U, Ewerbeck V, Thiesen HJ.18F-FDG kinetics and gene expression in giant cell tumors.
J Nucl Med. 2004 Sep;45(9):1528-35.
Strauss LG, Koczan D, Klippel S, Pan L, Cheng C, Willis S, Haberkorn U, Dimitrakopoulou-Strauss A.Impact of Angiogenesis-Related Gene Expression on the Tracer Kinetics of 18F-FDG in Colorectal Tumors.
J Nucl Med. 2008 Aug;49(8):1238-1244.
IEEE Trans Med Imaging. 2007 Jun;26(6):804-12.