Search results for "Neurotensin receptor"
showing 5 items of 5 documents
Positron Emission Tomography Imaging of Neurotensin Receptor-Positive Tumors with 68 Ga-Labeled Antagonists: The Chelate Makes the Difference Again
2021
Neurotensin receptor 1 (NTS1) is involved in the development and progression of numerous cancers, which makes it an interesting target for the development of diagnostic and therapeutic agents. A small molecule NTS1 antagonist, named [177Lu]Lu-IPN01087, is currently evaluated in phase I/II clinical trials for the targeted therapy of neurotensin receptor-positive cancers. In this study, we synthesized seven compounds based on the structure of NTS1 antagonists, bearing different chelating agents, and radiolabeled them with gallium-68 for PET imaging. These compounds were evaluated in vitro and in vivo in mice bearing a HT-29 xenograft. The compound [68Ga]Ga-bisNODAGA-16 showed a promising biod…
Neurotensin up-regulation is associated with advanced fibrosis and hepatocellular carcinoma in patients with MAFLD
2020
Background & aims: Neurotensin (NTS), a 13-aminoacid peptide localized in central nervous system and gastrointestinal tract, is involved in lipid metabolism and promotes various cancers onset mainly by binding to neurotensin receptor 1 (NTSR1). Increased plasma levels of pro-NTS, the stable NTS precursor, have been associated with type 2 diabetes (T2D), cardiovascular diseases and metabolic associated fatty liver disease (MAFLD). We aimed to evaluate 1) the impact of NTS rs1800832 and NTSR1 rs6090453 genetic variants on liver damage in 1166 MAFLD European individuals, 2) the relation between NTS variant and circulating pro-NTS and 3) the hepatic NTS expression by RNAseq transcriptomic a…
Design of Bimodal Ligands of Neurotensin Receptor 1 for Positron Emission Tomography Imaging and Fluorescence-Guided Surgery of Pancreatic Cancer
2020
International audience; Neurotensin receptor 1 (NTSR1) is overexpressed in most human pancreatic ductal adenocarcinomas. It makes it an attractive target for the development of pancreatic cancer imaging agents. In this study, we sought to develop a bimodal PET-fluorescent imaging agent capable of specifically targeting these receptors. Starting from the structure of a known NTSR1 agonist, a series of tracers was synthesized, radiometalated with gallium-68 and evaluated in vitro and in vivo, in mice bearing an AsPC-1 xenograft. PET imaging allowed us to identify the compound [ 68 Ga]Ga-NODAGA-Lys(Cy5**)-AEEAc-[Me-Arg 8 , Tle 12 ]-NT(7-13) as the one with the most promising biodistribution pr…
From Bench to Bedside—The Bad Berka Experience With First-in-Human Studies
2019
Precision oncology is being driven by rapid advances in novel diagnostics and therapeutic interventions, with treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations. Inherent in the theranostics paradigm is the assumption that diagnostic test results can precisely determine whether an individual is likely to benefit from a specific treatment. As part and integral in the current era of precision oncology, theranostics in the context of nuclear medicine aims to identify the appropriate molecular targets in neoplasms (diagnost…
Regulation of NT Receptors after Chronic Treatment with Typical and Atypical Neuroleptic Drugs
1991
Neurotensin is a tridecapeptide, which produces central effects such as hypotension, hypothermia, muscle relaxation, analgesia, antinociception, and reduces locomotor activity (Nemeroff et al., 1977). In the recent years, several lines of evidences indicated the great importance of the dopamine (DA)- neurotensin (NT) interaction taking place mostly in the mesolimbocortical areas, both at cell bodies (A10 DA-ergic group located in the ventral tegmental area -VTA-) and nerve terminal level (cerebral cortex, n. accumbens, olfactory tubercle, ventral n. caudato-putamen) (Quirion, 1983; Nemeroff, et al., 1984; Nemeroff, 1986). Immunocytochemical data indicated the presence of NT-like immunoreact…