China
Africa
Explore chapters and articles related to this topic
Use of Radioactivity in Drug Disposition Studies
Published in Francis L. S. Tse, James M. Jaffe, Preclinical Drug Disposition, 2017
Francis L. S. Tse, James M. Jaffe
Liquid scintillation counting is the most popular technique for the detection and measurement of radioactivity. In order to count a liquid specimen such as plasma, urine, or digested blood or tissues directly in a liquid-scintillation spectrometer, an aliquot of the specimen is first mixed with a liquid scintillant. Aliquots of blood, feces, or tissue homogenates are air-dried on ash-free filter papers and combusted in a sample oxidizer provided with an appropriate absorption medium and a liquid scintillant prior to counting. The liquid scintillant plays the role of an energy transducer, converting energy from nuclear decay into light. The light generates electrical signal pulses which are analyzed according to their timing and amplitude, and are subsequently recorded as a count rate, e.g.,counts per minute (cpm). Based on the counting efficiency of the radionuclide used, the count rate is then converted to the rate of disintegration, e.g., disintegrations per minute (dpm), which is a representation of the amount of radioactivity present in the sample.
Scintillation Counting
Published in Graham Lappin, Simon Temple, Radiotracers in Drug Development, 2006
This chapter describes the theory and practice behind the detection and measurement of radioactivity using scintillation counting. Both positron emission tomography (PET) and γ-scintigraphy utilize scintillation effects but these are rather specialized techniques and so they are dealt with separately (Chapter 11 and Chapter 12, respectively). Scintillation counting is inextricably linked to the instrumentation, with different manufacturers developing their own technologies and methods of data processing. Indeed, many innovations have arisen in the field of scintillation counting as a result of fierce competition among the manufacturers. The present chapter however, as far as possible, deals with the general principles of scintillation counting. The development, history, and idiosyncrasies of the instrumentation are covered in Chapter 8. The reader should be familiar with Section 2.3, which describes modes of radioactive decay. Sample preparation is covered in Chapter 9 and the statistics behind scintillation counting are covered in Chapter 7.
Preparation of Samples for Liquid Scintillation and Gamma Counting
Published in Howard J. Glenn, Lelio G. Colombetti, Biologic Applications of Radiotracers, 2019
Solubility in toluene or xylene imposes severe limitations on the liquid scintillation counting system. These limitations have sometimes been overcome by the use of the gel counting technique. In general, a sample of uniform particle size is prepared and suspended in a liquid scintillation solvent system containing a gelling agent such as Hylene TM-65, Armeen® L-11, aluminum stearate, thixin, or Cab-O-Sil®. Thixin (ricinoleic acid) is a castor oil derivative; Cab-O-Sil® is a uniformly finely divided silica. Cab-O-Sil® is most commonly used in 3.5% to 4.0% concentration, at which maximum counting efficiencies are obtained. Above this concentration range, the silica particles interfere with light transmission; below this concentration the gel is unstable. For solids, the sample should be finely powdered. It should not be partially soluble in the scintillation fluid; otherwise, the dissolved material is counted at a different efficiency than the suspended material. Advantages of this method of sample preparation for liquid scintillation counting are: (a) simplicity; (b) the ability to count large amounts of sample; and (c) minimum solvent quenching because the sample is not in solution. Inconsistency in counting efficiency may be caused by (a) suspension settling causing an immeasurable departure from 4π counting geometry; (b) medium opacity that increases light scattering; and (c) self-absorption, which makes the direct determination of counting efficiency impossible. Self-absorption causes a loss in emitted radiation, thereby decreasing the amount of radiation available for interaction with the liquid scintillant. For samples that are not uniform in particle size, the amount of self-absorption will vary between samples. Samples of this nature must therefore be ground and sieved to uniform particle size, a procedure that is time consuming and may give rise to much radioactive contamination. Two counting efficiencies must be determined; that of the emitted radiation that does react with the scintillator and that caused by self-absorption radiation loss. The latter may only be estimated by counting in suspension a material of known specific activity, and the loss in counting obtained by difference. The former, the counting efficiency of radiation that does react with the scintillant, may be determined by any of the methods used for homogeneous solution counting. The ratio of efficiency of suspension counting to that of homogeneous counting is known as the f-value,10 which varies with the particle size and the specific radioactivity of the suspended material. Suspension counting with f-values as high as 0.99 and as low as 0.12 has been reported.41
Predictive value of HDL function in patients with coronary artery disease: relationship with coronary plaque characteristics and clinical events
Published in Annals of Medicine, 2022
Marco Magnoni, Daniele Andreini, Angela Pirillo, Patrizia Uboldi, Roberto Latini, Alberico L. Catapano, Aldo P. Maggioni, Giuseppe D. Norata
To evaluate SR-BI-mediated cholesterol efflux, Fu5AH cells were grown to subconfluence, then incubated for 24 h with DMEM containing 5% FCS, 3H-cholesterol (1 µCi/ml), and 2 µg/ml ACAT inhibitor Sandoz 58-035. After washing, cells were incubated overnight in fresh DMEM containing 0.2% BSA and 2 µg/ml Sandoz 58-035. For efflux, cells were incubated with 1.5% plasma diluted in a serum-free medium for 4 h. The media were collected, centrifuged, and aliquots were used for liquid scintillation counting. Cell monolayers were lysed with 0.1 N NaOH and aliquots were used for liquid scintillation counting. The efflux of 3H‐cholesterol was calculated as the ratio of radioactivity released into the medium to the total (medium-plus intracellular) radioactivity. To correct for inter-assay variation across plates, a pooled plasma control from two healthy volunteers was included in each plate, and values for plasma samples from patients were normalised to this pooled value in all analyses. Intra- and inter-assay coefficients of variation for SR-BI-mediated cholesterol efflux were 4.7% and 14.3%, respectively.
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
Radioactivity in plasma and urine was analysed by liquid scintillation counting (LSC) on a liquid scintillation analyser (Tri-Carb 4910TR, PerkinElmer Life and Analytical Sciences, Downers Grove, IL). Plasma and urine were mixed with scintillant and counted directly. Radioactivity in whole blood and faeces was also assessed by LSC. Whole blood samples and faecal homogenates were combusted in a biological oxidiser (HTC-501, Hualida Laboratory Equipment Co., Ltd.). The [14C]-labelled carbon dioxide released was trapped in scintillation fluid. Radioactivity was determined by liquid scintillation counting as specified above. Lower limits of quantification (LOQ) of total radioactivity were expressed as nanogram equivalent [14C] cetagliptin per gram of blank matrix. They accounted for 306 ng Eq./g (faeces), 91.8 ng Eq./g (urine), 184 ng Eq./g (whole blood) and 46.8 ng Eq./g (plasma).
Assessment of drug-drug interactions of CC-90001, a potent and selective inhibitor of c-Jun N-terminal kinase
Published in Xenobiotica, 2021
Zeen Tong, Allison Gaudy, Daniel Tatosian, Francisco Ramirez-Valle, Hong Liu, Jian Chen, Matthew Hoffmann, Sekhar Surapaneni
CC-90001 was also assessed for inhibitory potential on OAT1, OAT3, OCT2, OATP1B1, and OATP1B3 using transporter-expressing cell lines. Incubations with prototypical substrates [3H]p-aminohippuric acid (PAH, 1 µM) for OAT1 (2 min), [3H]estrone sulphate (ES, 50 nM) for OAT3 (2 min), [14C]metformin (10 µM) for OCT2 (5 min), and [3H]Estradiol 17β-D-glucuronide (E217βG, 50 nM) for OATP1B1 and OATP1B3 (2 min) were performed in the presence or absence of CC-90001 (0.1, 0.3, 3, 10, 30 and 100 µM). Known inhibitors of each transporter (100 µM probenecid for OAT1 and OAT3, 300 µM quinidine for OCT2, and 10 µM rifampicin for OATP1B1 and OATP1B3) were included as positive controls. In studies using radiolabeled drugs and reagents, radioactivity was measured using a Tricarb 4910TR liquid scintillation counting (LSC) (PerkinElmer, Shelton, CT).