Axes de recherche
Increasing radiotracer uptake in neuroendocrine tumors via new signalling pathways and inducers: implementation into radio-theranostics
Background
Metastatic neuroendocrine tumors are rare neoplasm that are becoming more commonly detected with the progress of imaging techniques (123I-MIBG and somatostatin analogs scintigraphy). However, the progress of classical therapies have been disappointing with modest survival rate recorded at 5 years. Our findings have highlighted the rational of using several inducers of MIBG transporters and somatostatin receptors to improve radiopharmaceuticals uptake and binding on tumoral cells to improve theranostics (imaging and treatment) in patients affected by malignant neuroendocrine tumors. Our approach is based on preclinical model (cell lines and xenografted mice) with the aim to rapidly set up clinical trials.
Methods and proposed studies: The first step of this project consists of a continuation of the previous SNF project which involves experiments on different neuroendocrine tumor cells lines (MTT, MPC, NT-3 and TT cell lines) expressing MIBG transporters and somatostatin receptors (SSTRs). HDACi and inhibitors of the PI3K/Akt/mTOR signaling pathway (termed as “inducers”) will be tested on the cell lines for their ability to increase MIBG transporters and SSTRs. HPLC-MS/MS will be used to quantify the internalized MIBG and somatostatin analogs in the cell lines incubated with the identified inducer. Xenografted mouse model will be established (in collaboration with the Univ. of Basel, Prof. Fani) to confirm in vivo the increase in 123I-MIBG and somatostatin analogs uptake at tumor sites after (pre)treatment with the inducers identified. Biodistribution studies using 123I-MIBG and somatostatin analogs will be performed in different experimental settings. The therapeutic efficacy of a combined treatment using the inducers along with 131I-MIBG and somatostatin analogs will be assessed in the mouse model, by evaluating survival rate and toxicity (histopathologically) under the selected treatment protocol.
