Abstract ED4-2: Functional imaging: Getting beyond FDG-PET
Authors: de Vries EGE , Munnink T.H. Oude , Nagengast W.B. , Brouwers A.H. , Dieckx R.A. , Schröder C.P. , Lub-de Hooge M.N. 
Published: January 2011

Abstract
Molecular imaging of metabolism and drug targets in the tumor may well be of additional value in the treatment of cancer patients. It can potentially be used for screening, ((pre) operative) staging, restaging and guiding targeted therapies.
Molecular imaging is still in its infancy. It can be performed with various imaging modalities. Tracers used for this purpose can be labeled with either a contrast agent for magnetic resonance imaging (MRI), a fluorescent dye for optical imaging, or a radioactive nuclide for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging. We will focus on PET and SPECT imaging given their sensitivity and available results.
Most data are gathered on the visualization of general processes such as glucose metabolism and DNA synthesis. The PET-tracer [18F]fluorodeoxyglucose (FDG) is a glucose analogue and is used to visualize glucose metabolism, which is often increased in cancer cells. Increased DNA synthesis can be imaged with the pyrimidine analogue PET-tracer [18F]fluoro-L-thymidine (FLT), where FLT tumor uptake reflects the proliferation rate of cancer cells. With the increasing knowledge of the molecular processes that drive cancer and the introduction of the molecular targeted drugs, interest has been raised to image characteristics of tumor cells such as hormone receptors, growth factors and growth factor receptors. Molecular imaging of these characteristics can provide serial non-invasive information about the status of these characteristics within the tumor and its micro-environment and across lesions in the entire body when whole body imaging is performed. This is of interest as these characteristics can change over time and vary across lesions.
Molecular imaging of the ER with the PET tracer 16-α-[18F]fluoro-17-β-estradiol (FES) has shown a good correlation between FES tumor uptake and ER density. This tracer is currently being tested for various applications in clinical trials.
The field of visualizing growth factors and growth factor receptors is evolving rapidly. We imaged HER2 in breast cancer patients with the SPECT tracer 111In-trastuzumab and recently also with the PET tracer 89Zr-trastuzumab. With 111In-trastuzumab SPECT we showed that in 13 out of 15 patients with metastatic HER2 overexpressing disease more lesions were detected than with conventional staging procedures. Additionally the PET tracer 89Zr-trastuzumab shows excellent, quantifiable, and specific tumor uptake. In addition, we have developed 111In-bevacizumab for SPECT and 89Zr-bevacizumab for PET-imaging of vascular endothelial growth factor (VEGF) activity as an angiogenic marker. In melanoma patients small tumor lesions proved to be clearly visible with 111In-bevacizumab.
Apart from using these techniques for staging and determination of drug targets, it is possible to evaluate modulation of these targets by drugs. Both HER2 and VEGF are downregulated by inhibitors of the heat shock protein (HSP) 90 and imaging of their expression was preclinically in vivo an excellent readout for the early molecular tumor response to HSP90 inhibitors. This is currently translated to clinical trials. Lastly, tracers for the receptors EGFR, IGF-1R, and the ligand TGFβ and are under development. Supported by grants from Dutch Cancer Society, Pink Ribbon and Pink Ribbon Gala.
Citation Information: Clin Cancer Res 2010;16(7 Suppl):ED4-2