In this context, cancer specific receptors, which are over expressed ideally on the surface of cancer cells, have attracted considerable attention as tumour markers. If conjugated to contrast reagents or dyes, ligands for cancer specific receptors can guide marker moieties to a tumour site and allow the sensitive detection of cancer (see Fig. 1).

In this context our work addresses two major points:

1. Design and synthesis of ligands for established tumour markers such as the prostate specific membrane antigen (PSMA).

2. Development of new methods for studies of cell / small molecule interactions and their application to the search for new tumour markers on the surface of cancer cells.

Prostate cancer accounts for most cancer deaths in western industrialized countries. It has been found that about 30 % of all men above the age of 50 carry at least a latent prostate tumour (Robert Koch Institute). In this context, the sensitive detection of prostate tumours for early diagnosis or surgery of the disease is an unresolved problem.

We have designed high affinity (nM) low molecular weight ligands for PSMA based on conformationally constrained analogs of the natural PSMA-substrate N-Ac-aspartyl glutamate. These ligands are modular and can be conjugated to contrast agents for tumour imaging without loss of binding affinity.

We have developed new biomimetic multivalent platforms for prostate tumour targeting based on rigid scaffolds. The design of these platforms has been inspired by analogy to natural polyvalent cell surface binders such as the influenza virus and leads to fundamentally new rigid scaffolds based on adamantane. It improves pharmacokinetics and binding characteristics of low molecular weight ligands for the prostate specific membrane antigen, a well established marker on the surface of malignant prostate cancer cells.

In cooperation with Prof. John V. Frangioni (Harvard Medical School) we will transfer the concept into animal models and are finally aiming at the development of highly specific diagnostics for prostate cancer. As contrast agents we prefer NIR-fluorescence dyes, since they are non toxic, commercially available, water soluble and permit sufficient penetration into live tissues (up to a few centimetres).

Resolving one of the biggest drawbacks in current prostate cancer treatment, these devices will be particularly valuable for intraoperative prostate cancer imaging. They will thus improve problematic prostate cancer surgery and hopefully reduce the serious loss of life quality for surgery patients.