PET radiochemistry, in particular of pharmaceuticals

My research can be divided in three categories:

1. Immuno-PET of biopharmaceuticals

Immuno-PET imaging stands for PET imaging of antibodies and other emerging biopharmaceutical drugs and for this zirconium-89 (89Zr) is the preferred radionuclide that should be coupled stable and inertly to the biopharmaceutical via a so-called chelator. In recent years, my colleagues and I applied this in-house developed technique in numerous clinical trials supporting drug development and patient selection, and we further optimized the technology. To this end, we developed a new chelator for 89Zr, so-called DFO-star. Recently, we have shown in a preclinical setting that this new chelator is especially suited for PET imaging of antibodies used in Alzheimer’s Disease, when the antibodies are modified to be actively transported over the blood-brain-barrier (BBB). This is not possible when DFO, currently the gold standard for immuno-PET in oncology and inflammation, is used. Translational steps have been made to use this new chelator in three clinical phase I studies. Furthermore, we have developed methodologies for labeling oligonucleotides. Currently we are focussing on the labeling of new therapeutics such as cells.

2. New tracers for new targets.

At Tracer Center Amsterdam we focus on developing new PET tracers for emerging targets in oncology, neurology and immunology. The immune system plays a key role in disease progression and inflammatory targets are of great interest. In the past years my colleagues and I have successfully developed a pro-inflammatory microglial PET tracer targeting the P2X7 receptor from design to use in clinical research in MS and PD patients. In addition, we are developing a tracer targeting anti-inflammatory microglia. 

3. New radiochemistry methodologies

The radiochemistry possibilities to synthesize small molecule PET tracers are limited, and therefore not all molecules can be labeled, which hampers the use of PET during drug development. In recent years we have developed new ¹¹C-radiolabeled reagents and methods, as well as ¹⁸F-labelled triflyl fluoride, trifluoromethane and Ruppert-Prakash reagent to introduce ¹¹C or ¹⁸F in new efficient ways to access new PET tracers.