Synthesis, in vitro and in vivo evaluation of F-fluoronorimatinib as radiotracer for Imatinib-sensitive gastrointestinal stromal tumors.

Introduction: Gastrointestinal stromal tumors (GIST) have a wide range of mutations, but can mostly be treated with Imatinib, until eventually resistance towards this tyrosine kinase inhibitor is acquired. Early and non-invasive determination of the sensitivity of the tumor and its metastases towards Imatinib by positron emission tomography (PET) would be beneficial for therapy planning and monitoring.

Methods: We developed a synthesis strategy towards the precursor molecule, performed the F-synthesis and in the following evaluated the radioligand in vitro regarding its lipophilicity, stability and biological activity (KIT binding properties) as well as its in vivo properties in GIST tumor-bearing mice.

Role of LIM and SH3 protein 1 (LASP1) in the metastatic dissemination of medulloblastoma.

Medulloblastoma is the most common malignant pediatric brain tumor and is one of the leading causes of cancer-related mortality in children. Treatment failure mainly occurs in children harboring metastatic tumors, which typically carry an isochromosome 17 or gain of 17q, a common hallmark of intermediate and high-risk medulloblastoma. Through mRNA expression profiling, we identified LIM and SH3 protein 1 (LASP1) as one of the most upregulated genes on chromosome 17q in tumors with 17q gain.