You are here:

Functional biological imaging

Research area 2

A concept of four-dimensional (4D) radiotherapy is emerging, in which the biological and anatomical changes occurring during the 6-7 weeks that are used to deliver curative radiotherapy, is taken into consideration. Considerable organ motion and tumour regression often occur during treatment, which may necessitate renewed target definition, especially if inhomogeneous dose distributions are used. Currently, little is known about the kinetics of significant radiobiological processes such as reoxygenation and repopulation which could be tackled by an adaptive irradiative approach.
In the CIRRO project, functional imaging will be evaluated: 1) for assessment of tumour topography, 2) for assessment of biological tumour characteristics, 3) for characterising dynamics in tumours during radiotherapy, and 4) as predictive parameter for response to treatment. The long-term objective is to relate our findings to clinical outcome and apply the knowledge for planning of individualized radiotherapy.
Operable patients (head and neck and cervical cancer) will undergo functional biological imaging performed immediately before surgery, thus allowing for the comparison between the functional imaging parameters and measurements from blood and tumour samples (WP04, IP01). Biological and anatomical changes over time will be assessed by repetitive functional biological imaging (MRI and PET-CT) performed both before, during and after treatment with radiotherapy (WP04, IP01, IP11). Preclinical studies (WP02) will include multitracer PET imaging with markers for: hypoxia (18FAZA, 18FMISO, 64Cu-ATSM, 62Cu-ATSM), perfusion (H215O), proliferation (18F-FLT) and metabolism (18FDG, 11C-methionine). The techniques involving the newly developed 18FAZA have already been established in preclinical settings.
We hypothesize that by characterizing multiple aspects of tumour physiology and their spatial and temporal linkage a more robust prognostic metabolic and/or microenvironment tumour signature can be generated. For clinical PET-CT studies the functional imaging agents will be choline (IP08), hypoxia-markers 18FAZA, 18FMISO and 64Cu-ATSM (WP02, WP04, IP01), IP11, IP13. New MRI protocols, spectroscopy and nano particle contrast agents will be applied (WP04, IP12): diffusion weighted MRI, 18F oximetry and first pass DCE-MRI tracer kinetics for obtaining information about different aspects of topography, hypoxia and vascularity, respectively. Susceptibility MRI using an iron oxide contrast agent provides other vascular information. At the experimental level, iron oxide particles are being targeted against specific proteins (e.g., angiogenetic factors). Prognostic/predictive value of functional imaging will be investigated in both pre-clinical (WP02) and clinical settings (IP01,IP11, IP13). Tools for image management (developed in WP03) will be used for advanced image fusion and for modeling of changes in morphology and biology.