Faculty: Günter Allmaier
Radiopharmaceuticals, meaning drugs that contain radioactive isotopes, are mainly used for imaging applications (e.g. positron emission tomography, PET) in the diagnosis of tumors, metastases and neurological conditions. These imaging techniques are able to visualize dynamic metabolic processes, giving them advantage over classical x-ray examinations. Due to the short half-life of most commonly used positron emitters (18F: 108.9 min, 11C: 20.4 min) the production of radiopharmaceuticals is a challenging task and makes stock keeping of those medicinal agents impossible. The proposed project aims to address the problem of slow pharmocokinetics of available radiotracers by developing a pretargeted approach for PET imaging. Instead of using one radiolabeled probe, a two-stage imaging process will be applied:
- administration of a targeting marker (TM), which is specifically trapped in target tissue and
- administration of a radiolabeled pull down reagent (PDR) which selectively binds through a bioorthogonal reaction (click chemistry) to the non-radioactive TM in vivo.
Since substantially longer periods of time can be provided for enrichment of the TM in tumor areas, this novel method may lead to PET measurements with an unprecedented high image contrast in tumors compared to normal tissue (Figure). This approach will also enable the development of targeted radiotherapy, a prospective scientific breakthrough in the field of cancer research.
In parallel,mass spectrometry imaging (MSI) allowing the determination of the lateral distribution (low µm range by MALDI (matrix-assisted laser desorption ionization), high resolution mode compared to PET) of the TM in the specific tissues and organs on the molecular level before and after trapping (allowing also the determination of the macromolecules carrying the TM) will be performed. This will allow to evaluate at an early stage the suitability of selected TMs for later in vivo PET imaging. After the ligation of the PDR again IMS will be done to determine the distribution of the final reaction product and compare these data with PET images – allowing multimodal imaging which is of importance during the developmental stages of the outlined strategy.
- Synthesis of all compounds will be performed at the Institute of Applied Synthetic Chemistry (TU Vienna)
- Radiosynthesis, PET measurements and in vivo investigations with mice will be accomplished at the Austrian Institute of Technology (AIT). Cryosectioning of tumor-bearing mice treated with selected novel non-radioactive TM and radiolabeled PDR compounds will be done at AIT.
- The development of methods and strategies for subsequent molecular and elemental imaging will be done in collaboration with H. Hutter (TU Vienna).
- Combining PET and MSI data will be supported by R. Sablatnig (TU Vienna).