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Physics for medical imaging
Published in Ken Holmes, Marcus Elkington, Phil Harris, Clark's Essential Physics in Imaging for Radiographers, 2021
A good example of an atom with a number of isotopes is carbon, which has a total of 15 known isotopes. Carbon 12 is by far the commonest accounting for over 99% of all the carbon on earth. Three other well known isotopes of carbon are carbon 11, carbon 13 and carbon 14. These and other isotopes of carbon are unstable and undergo radioactive decay.
Case Investigation
Published in Kevin L. Erskine, Erica J. Armstrong, Water-Related Death Investigation, 2021
Carbon-14 or radiocarbon dating is a naturally occurring isotope of the element carbon, continually being formed in the atmosphere. Trace amounts of radioactive carbon are found in the natural environment. It is unstable and minutely radioactive. Carbon-14 dating was first used by archaeologists to estimate the age of certain objects between 500 and 50,000 years old. Radiocarbon content of terrestrial organisms is not the same as those of marine organisms because of the marine reservoir effect. Correction factors of the marine reservoir effect for different oceans in the world are established and recorded in a database. This procedure has recently found its way into technology to identify skeletal remains or other unidentified human remains. Nuclear weapons testing over the past 60 years has stirred up environmental levels of Carbon-14. From 1955 to 1963, levels almost doubled, and since that period of time, the levels have been tapering off to more normal.
Introduction and Method
Published in Christopher Cumo, Ancestral Diets and Nutrition, 2020
C3 and C4 pathways use different carbon isotopes. Isotopes of an element have identical chemical properties because the number of protons is constant but different masses because the numbers of neutrons differ. Most carbon, known as 12C, has 12 grams per mole, with a mole being a standard, huge number of atoms (6 × 1023). These 12 grams, the atomic mass, are the sum of carbon’s six protons and six neutrons in its nucleus. Carbon (13C) with seven neutrons has an atomic mass of thirteen, and carbon (14C) with eight neutrons has a mass of fourteen. Of these isotopes, 12C and 13C are stable and far more abundant in nature than 14C. Being unstable 14C decays into nitrogen. Being more numerous, 12C and 13C are available to form molecules, including the carbon dioxide that plants absorb, with other elements. Because C3 plants absorb more 12C than do C4 plants, whatever eats more C3 than C4 plants fixes more 12C in bones and teeth. Consequently, people who ingest more C3 than C4 plants or more animals with this pattern of consumption yield skeletons and teeth with greater ratios of 12C to 13C. Such information, for example, distinguishes barley from millet eaters.
The metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C] cetagliptin in healthy volunteers
Published in Xenobiotica, 2022
Jinmiao Lu, Yicong Bian, Hua Zhang, Dong Tang, Xusheng Tian, Xinyi Zhou, Zengyan Xu, Yating Xiong, Zheming Gu, Zhenwen Yu, Tong Wang, Juping Ding, Qiang Yu, Jinsong Ding
When drugs are administered to living organisms, they undergo a series of events such as absorption, distribution, metabolism and excretion (ADME) and these events modulate the efficacy and toxicity of drugs. Understanding the clearance mechanism, distribution and the metabolic fate of a drug candidate in humans is a key factor in new drug development, registration and ultimate use. in addition to good pharmacological activity, ADME properties are crucial determinants of the ultimate clinical success of a drug candidate. Labelling compounds with carbon-14 or H-3 (tritium) is by far the most widely used technique and the choice is usually between these two isotopes when planning a human mass balance study (Penner et al. 2009). However, the pros of the tritium use are outweighed by the cons, notably, the lack of biological stability and isotopic effect (switching biotransformation pathway due to reaction kinetics) (Shaffer et al. 2006). In a drug development setting, 14C-labelling is used in the majority of ADME studies (Penner et al. 2009).
Remyelination therapies for multiple sclerosis: optimizing translation from animal models into clinical trials
Published in Expert Opinion on Investigational Drugs, 2021
Rujapope Sutiwisesak, Terry C. Burns, Moses Rodriguez, Arthur E. Warrington
In 2019, two studies raised controversy as to the cells of oligodendrocyte lineage that participate in remyelination within human MS lesions. Yeung and colleagues showed that there were few new oligodendrocytes born within human MS shadow plaques using carbon 14 dating [10]. This study suggests that remyelination in patients with MS is achieved by surviving oligodendrocytes, not from OPCs are typically targeted in animal models. Single nuclear RNA-seq analysis from postmortem MS lesions demonstrated wide heterogeneity of oligodendrocyte-lineage cells. The number of OPCs was lower, not only within MS lesions, but also within normal appearing white matter of patients with progressive MS [24]. To date, clinical trials of candidate remyelination-promoting agents have proven disappointing. The carbon 14 dating data may suggest two possible explanations. First, MS pathophysiology disrupts normal OPC function. Second, whatever limited remyelination occurs in pattern I and II lesions is mediated by surviving mature oligodendrocytes rather than OPCs.
Pharmacokinetics of the selective prostacyclin receptor agonist selexipag in rats, dogs and monkeys
Published in Xenobiotica, 2018
Tomohiko Ichikawa, Tetsuhiro Yamada, Alexander Treiber, Carmela Gnerre, Kiyoko Nonaka
After a single oral dose of [14C]selexipag to rats, the amount of radioactivity eliminated in the urine and faeces in the period 0–168 h after administration accounted for 5.8 and 89% of the dose, respectively (Table 1). After a single intravenous dose of [14C]MRE-269 to rats, the radioactivity in the urine and faeces accounted for 4.9 and 94% of the dose, respectively. In all groups, the mean total recovery of radioactivity, including the cage washings up to 168 h, was in the range of 95–99%. The radioactivity in the expired air was less than 0.1% after intravenous administration, demonstrating that the carbon-14 was in a metabolically stable position of the molecule. Biliary excretion was the major elimination pathway after intravenous administration of [14C]selexipag, accounting for 92% of the dose (Table 2). After oral administration, the biliary route was responsible for the clearance of 72% of the systemically available drug, as determined from the combined radioactivity in the bile and urine. Renal excretion was in the range of 3–6% irrespective of the dosing route. Cumulative excretion was in excess of 95% at the end of the 168-h collection period. The potential for enterohepatic recirculation of MRE-269 was investigated after intravenous administration of [14C]MRE-269 to bile-duct-cannulated rats (Table 3). Bile was collected from dosed (donor) animals for 3 h and re-infused into the duodenum of bile-duct-cannulated (receiver) animals. Almost 55% of the radioactivity administered was reabsorbed by the receiver rats.