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Preclinical and evaluation of [C]ORM-13070 as PET ligand for alpha-2C adrenergic receptor occupancy using PET imaging in non-human primates.
J Cereb Blood Flow Metab
October 2024
Bayer AG, Wuppertal, Germany.
This paper describes the preclinical validation of the radioligand [C]ORM-13070 and its tritiated analog for addressing selectivity and occupancy of the selective alpha-2C adrenergic receptor (αR) antagonist BAY 292 in the cynomolgus brain. BAY 292 is a novel drug candidate being developed for the treatment of obstructive sleep apnea (OSA) via binding to central αR. autoradiography studies with sections from non-diseased post-mortem human caudate revealed an excellent specific binding window (>80%) using [H]ORM-13070.
View Article and Find Full Text PDFInfluence of tritium exposure route on vegetation types at the Savannah River Site.
Environ Sci Process Impacts
October 2024
Savannah River National Laboratory, Aiken, SC 29808, USA.
Plant, soil, water, and other media from various locations at the Savannah River Site were measured for total tritium (T) content and T speciation to characterize T in these areas, as well as investigate its uptake behavior and the transport of T species in these media. This characterization included the isolation and measurement of T in tritiated water (HTO), and (when possible) exchangeable organic bound T (E-OBT) and non-exchangeable organic bound T (NE-OBT). Two areas of interest were investigated: (1) a holding pond with T-contaminated water and (2) open basins or streams with low to background levels of T.
View Article and Find Full Text PDFDeuteration and Tritiation of Pharmaceuticals by Non-Directed Palladium-Catalyzed C-H Activation in Heavy and Super-Heavy Water.
Angew Chem Int Ed Engl
November 2024
Department of Chemistry, Indian Institute of Technology Bombay Powai, Mumbai, 400076, India.
Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non-directed homogeneous Pd-catalysis. Aromatic C-H activation is achieved by a commercially available pyridine ligand.
View Article and Find Full Text PDFIntestinal absorption of sphingosine: new insights on generated ceramide species using stable isotope tracing in vitro.
J Lipid Res
June 2024
CarMeN Laboratory, Inserm U1060, INRAE UMR1397, Univ-Lyon, Université Claude Bernard Lyon-1, Pierre Bénite, France. Electronic address:
Dietary sphingomyelin (SM) has been reported to favorably modulate postprandial lipemia. Mechanisms underlying these beneficial effects on cardiovascular risk markers are not fully elucidated. Rodent studies showed that tritiated SM was hydrolyzed in the intestinal lumen into ceramides (Cer) and further to sphingosine (SPH) and fatty acids (FA) that were absorbed by the intestine.
View Article and Find Full Text PDFInfluence of irrigation approaches and spatial geolocation on tritium speciation, uptake and depuration.
Chemosphere
February 2024
Savannah River National Laboratory Aiken, SC, 29808, USA.
Article Synopsis
- Pine needles and tree cores from a tritium-contaminated forest at the Savannah River Site were analyzed to understand tritium levels and forms in different vegetation.
- The study found that tree ages ranged from 9 to 14 years, reflecting over half of the site’s 20 years of remediation efforts, while pine needles provided data from the last 1-2 years.
- Irrigation at the Mixed Waste Management Facility significantly increased tritium concentrations in pine needles compared to non-irrigated samples, with tree cores retaining different forms of tritium than the predominantly water-bound tritium found in pine needles.
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