Positron emission tomography (PET)

Research Group: Prof. Dr. Alfred Buck & Prof. Dr. Bruno Weber


Oxygen consumption is one of the very interesting parameters in many organisms and organs, both in physiology and pathology. Unfortunately, the non-invasive absolute quantification of the oxygen consumption is not easy. The Gold standard is positron emission tomography (PET) with labelled oxygen (15O2). The latter requires an on-site cyclotron, which is available only in a limited number of PET centres. The PET centre at the University Hospital Zurich has been operating since 1993, and includes a cyclotron for the required radioisotope production.
Normal FDG PET

In tumor therapy, the degree of oxygenation is of great importance for the success of radio- and chemotherapy. Hypoxic areas tend to be resistant to therapy. One of the aims of this project is to measure the oxygenation in tumors. A direct, but only semi-quantitative determination of oxygenation can be achieved with the hypoxia tracer 18F-MISO. However, this tracer is at present not available at the PET centre. We therefore chose a different approach. We will determine total glucose metabolism using 18F-fluorodeoxglucose (FDG) PET. In a second step total oxygen consumption in the tumors will be measured with 15O2 PET. From these 2 measurements the non-oxidative part of the tumor glucose metabolism will be determined. We hypothesize that this glycolytic part is directly related to the oxygenation of the tumor. Furthermore the amount of oxygen consumption itself may turn out to be a relevant parameter with respect to therapy response.

In work package 1, the methodology of 15O2 PET will be established at the PET centre of the University Hospital. To validate the method, we will examine 10 volunteers using a visual stimulation paradigm. The study is already approved by the ethics committee and the BAG and can therefore start soon. The validation phase will be finished at the end of 2013. Once the method is established the tumor projects will start. In a first clinical project, we will examine patients with head and neck or brain tumors before radiotherapy. In parallel, parameters related to oxygen metabolism will be measured using magnetic resonance techniques. Furthermore, hypoxic areas in tumors will be treated with higher radiation doses. Endpoints of this part are the relationship of the progression free survival period and tumor oxygen consumption, and the relationship between the PET and the MR measurements. The latter are much more available. Therefore, it would be advantageous if oxygen consumption related measurements could be performed with MR. Further, similar protocols will be followed in patients with head and neck tumors before undergoing surgery or chemotherapy.

The evaluation of total glucose metabolism using FDG PET is well established. The PET centre routinely performs 20-30 such PET scans each day. The oxygen consumption measurements using 15O2 PET have been used in many PET centres all over the world and there is a vast body of literature regarding the technical details of the scans and the data analysis. Most of the software needed for the data analysis is readily developed and installed. As mentioned above the first study is in healthy human volunteers, the second and third study will be performed in tumor patients.
The clinical group of the KFSP will refer the patients to us. Patient monitoring, treatment control etc. will be performed by the clinicians involved in the KFSP. Dr. Boss (Dept. of Radiology USZ) will use carbogen BOLD MRI to investigate tumor oxygenation. This is an alternative novel method that we will cross-validate with our measurements.

Significance
PET will provide essential information on the oxygenation and metabolism of tumors for many research projects within the KFSP Tumor Oxygenation.