As the blood-brain barrier (BBB) seems to be a major hurdle in the treatment of children (and adults) with malignant brain tumors, research in the group focuses on new possibilities to circumvent or better cross this barrier. Several research projects in the Van Vuurden Group are currently exploring these new avenues of drug delivery
Focused Ultrasound Mediated Blood Brain Barrier Opening
KWF-STW project 15184 (PhD student: Rianne Haumann) studies the use of ultrasound waves, in combination with microbubbles in the bloodstream, to allow for temporary opening of the BBB. In this way, drugs that normally do not exit the blood, can enter the brain region of interest, and result in higher drug concentrations in the brain tumor.
KWF project 10911 (PhD student TBA) the same approach (microbubble and ultrasound-mediated BBB opening) in combination with radiotherapy, to increase the uptake of radiosensitizers: drugs that render tumor cells more vulnerable to radiation. In combining these different therapeutic modalities, the translational aim of this research is to develop a clinical trial for children and adults with high grade gliomas.
Furthermore, the Van Vuurden group is involved in a European research project (EuroNanoMed III), in which the abovementioned opening of the blood-brain barrier by the use of soundwaves is studied more in depth with different nanotechnological materials to package drugs. In combining these new technologies, the aim is to even better deliver medication to the tumor site in the brain.
Convection Enhanced Drug Delivery
The treatment of patients with DIPG seems to specifically suffer from highly impaired drug delivery due to an intact BBB. Therefore, near-future clinical studies that are being developed study the use of microcatheters into the DIPG tumor for drug delivery (PhD student: Fatma El-Khouly). Via these catheters, drugs are infused over a long time period. This technique is called convection-enhanced delivery (CED). The Princess Máxima Center has set up a collaboration with colleagues from the UK that have pioneered with this innovative technique. Research in the laboratory will identify the optimal drugs/drug combinations to be used via these catheters. In 2019, the first patients are expected to be treated with CED in the Máxima.
Molecular Drug Imaging
Especially with the BBB as an important hurdle for effective therapies in pediatric neuro-oncology, it is of great importance to ascertain whether drugs actually reach the brain tumor. Using radio-isotopes, microdoses of drugs can be labeled and tracked in the body. Previous research has shown that using 89Zr coupled to bevacizumab (Avastin) in DIPG, no to limited and only very local uptake of the drug was visualized in the tumor. This very likely reflects the inability of especially large molecules to enter the tumor when the BBB is intact. Current imaging studies (PhD student: Fatma El-Khouly) are investigating 89Zr-bevacizumab in non-brainstem HGG, and another exploring the uptake of microdoses of smaller molecules such as Erlotinib in brainstem tumors, using 11C. These studies are performed in collaboration with VU medical center. Future aim is to develop more drug imaging studies in pediatric oncology patients, to ultimately distinguish patients who are likely to benefit from a therapy (e.g. showing drug uptake in the tumor) from those who do not.