Marika Nestor – Head and neck tumour targeting

The aim of our research is to find an efficient method for diagnosis and therapy of head and neck cancer. We focus on developing the use of radioactive nuclides for localising and treating metastasised tumours, with the aim to improve the survival of this group of patients.

In Sweden approximately 1000 cases of cancer in the mouth or throat are discovered each year. This is a type of cancer that is relatively difficult to treat since it often spreads to other parts of the body, and around 50 per cent of the patients eventually die from their disease. Radiation and/or surgery are standard therapies for these tumours but these methods are not sufficient for localising or treating metastasised tumour cells today.

Targeting tumours with radioactively labelled molecules

We are focusing on molecular targeting of head and neck tumours using radioactively labelled molecules. This is a promising method to selectively detect, localise and treat metastasised cancer cells.

To use this method both suitable targets on the tumour cells and appropriate targeting agents, that can detect the targets, are required. In addition, radioactive nuclides (also called radionuclides) are needed, that can be used to label the targeting agents. The radiolabelled molecules will then circulate in the body and bind to the tumour cells. The radioactivity enables us to either detect the radiolabelled molecules and subsequently show us where the tumour cells are by using PET or SPECT cameras, or to selectively kill the tumour cells, depending on which radionuclide we use.

The concept of radio-immunotargeting
A radiolabeled compound binds to a target that is overexpressed on the surface of tumor cells, while normal cells do not (or to very small extent) express the target. Thus, the radionuclide will accumulate on tumor cells but not in normal tissue.

Identifying target molecules

A basic requirement for targeting tumours is to identify suitable structures on the tumour cells that can be used as targets. Optimally such structures are present at high levels in tumours, and at low levels or not at all in normal tissues.

We are therefore studying the presence and distribution of specific proteins on the surface of tumour cells, for instance different forms of the protein CD44, which is overexpressed on tumour cells. Furthermore, these proteins can also be associated with different properties of the tumour cells, such as radio-resistance or metastatic potential. This is an important future part of individualized cancer therapy, where the tumour of a patient can first be characterized for the presence of these proteins, to help guide the choice of treatment that will best suit the individual patient.

Development of targeting agents

Antibodies have been used as tumour targeting agents for a long time but due to their large size they are not optimal for diagnostics using radionuclides. We are therefore investigating how antibody fragments and other small proteins can be used to target molecules on tumour cells.

Different radionuclides and labelling methods

We are also evaluating how different radioactive elements and labelling techniques can be used to label the targeting agents. Radionuclides with different half-lives and decays must match the targeting agent and the intended application. We also work with optimising the labelling reactions by varying e.g. pH, reaction time and temperature. It is important to find a labelling method that is fast and efficient, but that will not damage the binding properties of the targeting agent.

More information about our research projects