Ph ceremony: Ms. I. Farinha Antunes, 14.30 uur, Aula Academiegebouw, Broerstraat 5, Groningen
Disseration: Development and evaluation of PET tracers for imaging B-glucuronidase activity in cancer and inflammation
Promotor(s): prof. R.A.J.O.Dierckx, prof. H.G. Haisma, prof. P.H. Elsinga
Faculty: Medical Sciences
The ideal treatment should cure a disease without harming healthy tissues. Therefore, a new treatment strategy for cancer and certain inflammatory diseases has been developed called Prodrug therapy. In this approach, a toxic drug is “disguised” as a non-toxic compound called prodrug, which can be reactivated by an enzyme at the target site, releasing the drug only where it is needed. β-Glucuronidase is being explored as an enzyme to activate prodrugs. Not every patient possesses the same amount of β-glucuronidase at the target site. PET imaging of β-glucuronidase activity could allow monitoring β-glucuronidase activity over time. Provided that a suitable tracer is available, PET might give information about the levels of β-glucuronidase present in various tissues in a patient. Thus, PET might be used to predict which patients would benefit from β-glucuronidase prodrug therapy.
The aim of this project was to develop a PET tracer for imaging β-glucuronidase activity and to use it for evaluation of β-glucuronidase in animal models for various disorders. Our in vivo studies show that the PET tracer [18F]FEAnGA can detect and quantify extracellular β-glucuronidase activity in tumors, in sterile inflammatory lesions and in brain infection. We were also able to demonstrate with [18F]FEAnGA PET that a single dose of cytostatic drug can increase β-glucuronidase activity in tumors. This study may open the way to a two-step chemotherapy-prodrug approach, in which tumors are treated with a single dose of a cytostatic drug to increase the levels of β-glucuronidase prior the prodrug treatment.
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