Résumé
In nuclear medicine, the diagnosis and therapy, targeting G protein-coupled receptors (GPCRs) with radiolabeled peptides is a topic of major importance, because several receptors are overexpressed in many cancers. Indeed, since a metastatic disease can be successfully imaged by Positron Emission Tomography (PET), the patient might then benefit from targeted radionuclide therapy (TRT) using the same ligand, radiolabeled with a therapeutic radionuclide such as 177 Lu. In this field, the neurotensin receptor-1 (NTS1) has been identified as an excellent target within primary tumor and lymph nodes metastases for selected prostate and breast cancer patients with poorer prognosis. [1] For our contribution in this area, we have reported a promising class of radiopharmaceuticals based on neurotensin NT[8–13] analogue conjugates radiolabeled with 68Ga and stabilized in vivo by the non-natural silylated amino acid (L)-Trimethylsilylalanine (TMSAla) and sequence modifications, for PET imaging of tumors overexpressing NTS1[2] or NTS2[3] receptors. In continuation of this work, we are developing NT[8–13] analogues for labeling with 18F, because its halflife of 110 min allows late imaging to visualize more lesions with a better signal/noise ratio. Herein, a novel radiolabeling strategy based on the introduction of a new class of silylated amino acid as pre-marker for [18F]-fluorination, by formation of a Si-18F bond in the final step will be reported. Other analogues obtained by coupling to an arylsilane moiety at the N-terminus position of the sequence, or to the NOTA chelating agent for radiolabeling with aluminum fluoridewill also be described. In vitro characterization of the corresponding radiopharmaceuticals is undergoing in NTS1-expressing HT-29 colon cancer cell line.