We describe the application of macroautoradiography, a relatively simple, quantifiable method for the evaluation of positron-emitting and gamma-emitting radiopharmaceuticals. We have investigated the response properties of two types of film to positron (F-18) and negatron (C-14) emitters. Variations in the response of film to increasing film-to-source distance are described, along with the effects of different intensifying screens and mounting tape. Digitization of whole-body autoradiograms (WBARG) in small animals was performed by using a videodensitometry system (videocamera interfaced to a computer). Quantitation was derived from analysis of a series of step-wedge standards that covered the range of radioactivities in the sample. By using a close-up lens on the videocamera, a 2- by 2-cm field is digitized as a 128 X 128 array, each pixel representing 156 X 156 micron. The effect of chlorpromazine (CPZ) on glucose metabolism in mice was studied by giving C-14 2DG followed by CPZ and F-18 FDG in the same animal. Muscle activity decreased and brown-fat activity increased. The high spatial resolution of this technique enables quantification in structures as small as the basal ganglia in mice. The use of dual-nuclide ARG permits each animal to be its own control, which greatly increases the utility of this method.
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Prog Neurobiol
December 2024
Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich 52425, Germany; C. & O. Vogt Institute for Brain Research, Heinrich-Heine-University, Dusseldorf 40225, Germany.
Neurotransmitter receptors are key molecules in signal transmission in the adult brain, and their precise spatial and temporal balance expressions also play a critical role in normal brain development. However, the specific balance expression of multiple receptors during hippocampal development is not well characterized. In this study, we used quantitative in vivo receptor autoradiography to measure the distributions and densities of 18 neurotransmitter receptor types in the mouse hippocampal complex at postnatal day 7, and compared them with the expressions of their corresponding encoding genes.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Holy Stone Healthcare, Preclinical and Development Div Hsinchu, Taipei, Taiwan.
Introduction: CA102N is a novel anticancer drug developed by covalently linking H-Nim (N-(4-Amino-2-phenoxyphenyl methanesulfonamide) to Hyaluronic Acid to target CD44 receptor-rich tumors. The proposed approach seeks to enhance the efficacy and overcome limitations associated with H-Nim, including poor solubility and short half-life.
Methods: The study aimed to evaluate the pharmacokinetics, biodistribution, metabolism, and tumor permeability of [14C] CA102N in xenograft mice following a single intravenous dose of 200 mg/kg.
PLoS One
December 2024
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Background: In tissue distribution studies of radiopharmaceuticals, quantitative whole-body autoradiography (QWBA) and oxidative combustion (OC) analysis are the two important methods that have not been compared using the same drug. Sprague-Dawley (SD) and Long-Evans (LE) rats, both of which are commonly used rodents in tissue distribution studies, have also not been compared using the same drug. Comparative studies are important for aiding the selection of appropriate experimental methods and animals.
View Article and Find Full Text PDFPsychoneuroendocrinology
January 2025
Core Centre for Molecular Morphology, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Clin Transl Sci
October 2024
Laboratory of Clinical Pharmacology, Yokohama University of Pharmacy, Yokohama-shi, Kanagawa, Japan.
The dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (LNG) exhibits target-mediated drug disposition (TMDD) in clinical settings, characterized by saturable binding to plasma soluble DPP-4 (sDPP-4) and tissue transmembrane DPP-4 (tDPP-4). Previous studies have indicated that saturable renal reabsorption of LNG contributes to its nonlinear urinary excretion observed in humans and wild-type mice, but not in Dpp-4 knockout mice. To elucidate the mechanisms underlying these complex phenomena, including DPP-4-related renal reabsorption of LNG, we employed physiologically-based pharmacokinetic (PBPK) modeling combined with a cluster Gauss-Newton method (CGNM).
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