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Preparation of Samples for Liquid Scintillation and Gamma Counting
Published in Howard J. Glenn, Lelio G. Colombetti, Biologic Applications of Radiotracers, 2019
When equilibrium has been obtained, the labeled bound antigen must be separated from the free labeled antigen by one of a large number of laboratory techniques, and either or both fractions assayed for radioactivity.51, 52 A standard curve must be developed using known amounts of antigen, and the unknown samples run at the same time under identical laboratory conditions. The test is an aqueous in vitro test, but the samples all contain proteinic substances. If liquid scintillation counting is used to measure the radioactivity in each sample, all the problems of sample solubility, quenching, and counting efficiency must be taken into account. Once the laboratory steps of separating the bound from the free radioactivity have been completed, the aqueous samples must be solubilized in liquid scintillation fluid using a high water capacity scintillant solution or sample precombustion or emulsion formation techniques.
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.
The Study of Drug Metabolism Using Radiotracers
Published in Graham Lappin, Simon Temple, Radiotracers in Drug Development, 2006
The volume of distribution is a useful parameter in the design of in vivo radiotracer studies. The volume of distribution for the parent drug may well be known from clinical trials or animal studies by the time the metabolism studies are performed. Let us say, for argument’s sake, that the volume of distribution for a particular drug was 100 L. If 3.7 MBq (2.22 × 108 dpm) was administered intravenously, then the plasma concentration at time zero (assumed to be the first sampling point after intravenous administration) will be 3.7 MBq in 100 L or 2220 dpm/mL. This radioactive concentration is easily detectable by liquid scintillation counting (Chapter 6). Imagine a situation, however, where 370 KBq of a drug with a volume of distribution of 1500 L was administered. Here the plasma concentration will be 14.8 dpm/mL, and this is likely to be too low to measure with liquid scintillation counting; another technique, such as accelerator mass spectrometry (Chapter 10), may be necessary.
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).