Work Package 4
Target Analysis and Molecular Probe Design
Starting from known molecules binding to alternative targets WP4 will develop new potential radiopharmaceuticals and synthesise imaging probes recognising specific epitopes on GIST tumour cells. After in vitro evaluation of binding properties the body distribution of the potential radiotracers will be evaluated in vivo in specific animal models by using a small animal PET-CT. Different derivatisation/labelling strategies will be used based on the results of the in vivo and in silico evaluation. A biorepository of naïve and treated/resistant GIST samples will be generated in a viable, cryopreserved state. For patient derived tumourgrafts (PDT) a mouse model of imatinib-resistant GIST will be developed based on highly immunocompromised and/or humanized mice (NSG).
Contributing Partners: UNITO, CAGE, AAA, HM
Duration: Month 1 – 48
1st Year`s Achievements
First data of Imatinib distribution in GIST biopsies using MS-imaging technique have been collected. Furthermore, strategies for the synthesis of promising precursors targeting GIST were established. Their synthesis and first in vitro evaluations are in progress. Recently, a GIST specific mouse model using immune compromised mice was set up, which forwards the work flow regarding the upcoming investigation of the new tracers in vivo. The translation of expected absorbed doses and the suitability of the tracers in human will be performed by in silico simulations using physiologically based pharmacokinetic models.