Determination Of Half-life Research Articles

Calculation of chemical elimination half-life from blood with an ongoing exposure source: The example of perfluorooctanoic acid (PFOA)

Determination of the chemical clearance rate from human blood is a critical component of toxicokinetic exposure assessment. Analysis of temporal biomonitoring data without consideration of ongoing exposure results in calculation of apparent elimination half-life values that are longer than the intrinsic value. The intrinsic elimination half-life is solely a function of the rate of elimination while the apparent elimination half-life reflects the processes of both elimination and ongoing exposure. Confusion between intrinsic and apparent half-life values can lead to misinterpretation of biomonitoring data and can result in exaggerated predictions in subsequent modeling efforts. This work provides a review of the first-order equations that have been developed to calculate intrinsic and apparent half-life values and the potential bias that can result from confusing these two values. Published human biomonitoring data for perfluorooctanoic acid (PFOA) are analyzed using these equations to provide examples of low, medium and high bias in determination of the intrinsic elimination half-life from plasma or serum, the components of blood typically analyzed for PFOA. An approach is also provided to estimate the extent of exposure reduction that is indicated by declining longitudinal or cross-sectional biomonitoring data. Based on the evaluation methodology presented in this work, the intrinsic elimination half-life of PFOA in humans is 2.4years, representing the average of independent estimates of 2.5years (95% CI, 2.4–2.7) and 2.3years (95% CI, 2.1–2.4). The declining concentration of PFOA in blood of the general USA adult population represents an estimated exposure reduction of 20–30% over the period 1999–2008.

A new determination of the 209Po half-life

A substantial 25% error in the then-known and accepted (102 ± 5) year half-life of 209Po was reported on in 2007. This error was detected from decay data from two separate primary standardizations of a 209Po solution standard, which were performed approximately 12 years apart. Despite author claims that this observation was not a new half-life determination, it was nevertheless included in subsequent nuclear data evaluations and compilations to obtain a currently tabulated value of (115 ± 13) a, computed from the median and range of the two half-life reports. A third primary standardization on the identical 209Po solution has since been performed to derive a new half-life value of (125.2 ± 3.3) a. This half-life determination was obtained from 30 distinct data sets over a period of 20.7 years, encompassing over 700 liquid scintillation measurements with nearly 50 counting sources all prepared from the same solution, and as obtained over a very broad range of measurement conditions (composition of cocktails, characteristics of counters, time sequencing) during five periods in 1993, 1994, 2005, and 2013.

Purification of a 166mHo solution by successive high-performance liquid chromatography and gravitational chromatography for half-life determination

A methodology to purify a 166mHo solution has been developed by a combination of activity and mass concentration measurements in order to further determine the 166mHo half-life. The isobaric interference at m/q ≃ 166 requires Ho purification from non-natural Er with a high purification degree due to the large amount of Ho as opposed to Er. The Ho/Er separation was achieved using high-performance liquid chromatography on a semi-preparative column followed by purification on gravitational chromatography. The efficiency of the separation was evaluated after precise determination of the Er isotopic composition. The purification methodology enabled to separate Ho from Er.

Sodium selenite enhances thyroid uptake of iodine-131 and regulates thyroid function in rats.

The aim of the present study was to evaluate the role of selenium (Se) on the thyroid uptake and retention of radioiodine ((131)I) and on the serum levels of thyroid hormones. Experimental rats were divided into four groups with 10 animals in each group viz: untreated controls, (131)II-treated, Se-treated and (131)I+Se-treated. Group II and Group IV animals were injected intraperitoneally with 3.7MBq of (131)I. Group III and Group IV animals received Se in the form of sodium selenite, everyday at a dose of 1ppm in drinking water. Thyroidal (131)II uptake measurements, determination of biological half life of (131)I and estimation of serum of tri-iodothyronine (T3) and tetra-iodothyronine (T4) and thyroid stimulating hormone (TSH) were carried out at two time intervals after 2 and 4 weeks. The statistical significance of the data was determined by using one-way analysis of variance (ANOVA) followed by Newman-Keuls test. The results showed lower serum levels of T3 and T4 and higher TSH levels in rats treated with (131)I when compared to untreated rats. Furthermore, the biological half life (Tbiol) of (131)I in thyroid and thyroidal (131)I uptake values at 2h and 24h were significantly lower in rats treated with (131)I compared with untrated control. Selenium treatment of (131)I treated rats resulted in a significant increase in the thyroid uptake as well as Tbiol of (131)I which indicated its increased retention. Moreover, normalization of the elevated serum TSH levels and a significant increase in the T3 and T4 levels was evident when Se was administered to the (131)I treated rats. In conclusion, this study indicates that Se when given to rats in the form of sodium selenite, at a dose of 1ppm in drinking water enhances the uptake and retention of (131)I in the thyroid as well as regulates thyroid hormone levels.

Alpha-decay of 184Os revealed by radiogenic 180W in meteorites: Half life determination and viability as geochronometer

The decay of the rare nuclide 184Os by alpha emission to 180W has been theoretically predicted, but was previously never observed in experiments. Variable excesses of 180W were recently observed for iron meteorites, but the contribution to these excesses by 184Os-decay was regarded as insignificant. Here, we present combined 180W and Os–W concentration data for meteorites and terrestrial rocks, now indicating that the 180W heterogeneities can be explained by α-decay of 184Os. A combined 184Os–180W isochron for iron meteorites and chondrites yields a decay constant value of λ184Os(α) of 6.49±1.34×10−14 a−1 (half life 1.12±0.23×1013 yr), in good agreement with theoretical estimates. The 184Os–180W decay system may constitute a viable tracer and chronometer for important geological processes like core formation, silicate differentiation or late accretion processes. This is illustrated by a measured 180W-deficit in terrestrial basalts relative to chondrites by 1.16±0.69 parts in 10 000, consistent with core formation ∼4.5 Ga ago.

Results of the EURAMET.RI(II)-K2.Ho-166m activity comparison

In 2013, five laboratories took part in the EURAMET.RI(II)-K2.Ho-166m comparison of activity concentration measurements of 166mHo. The activity measurements of this comparison are part of the joint research project 'Metrology for Radioactive Waste Management' of the European Metrology Research Programme (EMRP). One aim of this project is a new determination of the 166mHo half-life.The results were found to be in good agreement and no outlier could be identified. A comparison reference value (CRV) has been calculated as the power-moderated mean (PMM) of all final laboratory results and was found to be 119.27(10) kBq g-1. Preliminary degrees of equivalence based on the Comparison Refeence Value were also calculated for each reporting laboratory. The Key Comparison Reference Value and final degrees of equivalence will be calculated by the BIPM from the data contained herein and data from measurements made in the International Reference System (SIR). Main text.To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

Theory of nuclear half-life determination by statistical sampling

A remarkable method for measuring half-lives of radioactive nuclei was proposed several years ago that entailed statistical sampling of the source activity. A histogram of half-life estimates, calculated from pairs of activity measurements separated in time, took the unexpected form of a nearly perfect Cauchy distribution, the midpoint of which corresponded very closely to the true value of the half-life. No theoretical justification of the method was given. In this article I derive the exact probability density function (pdf) of the two-point half-life estimates, show how (and under what conditions) a Cauchy distribution emerges from the exact pdf —which, mathematically, shows no resemblance to a Cauchy function— and discuss the utility of the statistical sampling method. The analysis shows that the exact pdf, under the conditions leading to an empirical Cauchy lineshape, is an unbiased estimator of the true half-life.

Reprint of: Half-life determination for short-lived radioisotopes 52V, 66Cu and 28Al

In this work, the half lives of 52V, 66Cu and 28Al were measured using a non-paralyzable dead-time correction to the regular exponential decay. For 28Al, a physical dead-time correction was also employed to allow a verification of the mathematical correction used. The resulting values were 3.734(3)min for 52V and 5.061(6)min for 66Cu; as for 28Al, the results were 2.233(9) min using the non-paralyzable correction and 2.228(5)min using the secondary correction, thus validating the mathematical approach.

Quantitative pharmacological analyses of the interaction between flumazenil and midazolam in monkeys discriminating midazolam: Determination of the functional half life of flumazenil

The duration of action of a drug is commonly estimated using plasma concentration, which is not always practical to obtain or an accurate estimate of functional half life. For example, flumazenil is used clinically to reverse the effects of benzodiazepines like midazolam; however, its elimination can be altered by other drugs, including some benzodiazepines, thereby altering its half life. This study used Schild analyses to characterize antagonism of midazolam by flumazenil and determine the functional half life of flumazenil. Four monkeys discriminated 0.178mg/kg midazolam while responding under a fixed-ratio 10 schedule of stimulus-shock termination; flumazenil was given at various times before determination of a midazolam dose–effect curve. There was a time-related decrease in the magnitude of shift of the midazolam dose–effect curve as the interval between flumazenil and midazolam increased. The potency of flumazenil, estimated by apparent pA2 values (95% CI), was 7.30 (7.12, 7.49), 7.17 (7.03, 7.31), 6.91 (6.72, 7.10) and 6.80 (6.67, 6.92) at 15, 30, 60 and 120min after flumazenil administration, respectively. The functional half life of flumazenil, derived from potency estimates, was 57±13min. Thus, increasing the interval between flumazenil and midazolam causes orderly decreases in flumazenil potency; however, across a broad range of conditions, the qualitative nature of the interaction does not change, as indicated by slopes of Schild plots at all time points that are not different from unity. Differences in potency of flumazenil are therefore due to elimination of flumazenil and not due to pharmacodynamic changes over time.

What's your age again? Determination of human neutrophil half-lives revisited

Neutrophils are the most abundant white blood cells and are indispensable for host defense. Recently, they have also been implicated in immune regulation and suppression. The latter functions seem hard to reconcile with the widely held view that neutrophils are very short-lived, with a circulatory half-life of <7 h. To reopen the discussion on the average neutrophil half-life, we review and discuss experiments performed in the 1950s, 1960s, and 1970s, as well as recent in vivo labeling experiments. We reappraise the current knowledge on neutrophil half-lives, including their production in the bone marrow, their residency in the circulation and marginated pool, and their exit from the circulation.

Proteome-Wide Measurement of Protein Half-Lives and Translation Rates in Vasopressin-Sensitive Collecting Duct Cells

Vasopressin regulates water excretion, in part, by controlling the abundances of the water channel aquaporin-2 (AQP2) protein and regulatory proteins in the renal collecting duct. To determine whether vasopressin-induced alterations in protein abundance result from modulation of protein production, protein degradation, or both, we used protein mass spectrometry with dynamic stable isotope labeling in cell culture to achieve a proteome-wide determination of protein half-lives and relative translation rates in mpkCCD cells. Measurements were made at steady state in the absence or presence of the vasopressin analog, desmopressin (dDAVP). Desmopressin altered the translation rate rather than the stability of most responding proteins, but it significantly increased both the translation rate and the half-life of AQP2. In addition, proteins associated with vasopressin action, including Mal2, Akap12, gelsolin, myosin light chain kinase, annexin-2, and Hsp70, manifested altered translation rates. Interestingly, desmopressin increased the translation of seven glutathione S-transferase proteins and enhanced protein S-glutathionylation, uncovering a previously unexplored vasopressin-induced post-translational modification. Additional bioinformatic analysis of the mpkCCD proteome indicated a correlation between protein function and protein half-life. In particular, processes that are rapidly regulated, such as transcription, endocytosis, cell cycle regulation, and ubiquitylation are associated with proteins with especially short half-lives. These data extend our understanding of the mechanisms underlying vasopressin signaling and provide a broad resource for additional investigation of collecting duct function (http://helixweb.nih.gov/ESBL/Database/ProteinHalfLives/index.html).

Determination of the half-life of213Fr with high precision

High-precision measurement of half-life and ${Q}_{\ensuremath{\alpha}}$ value of neutral and highly charged $\ensuremath{\alpha}$ emitters is a major subject of investigation currently. In this framework, we recently pushed half-life measurements of neutral emitters to a precision of a few per mil. This result was achieved by using different techniques and apparatuses at Istituto Nazionale di Fisica Nucleare Laboratori Nazionali del Sud (INFN-LNS) and GSI Darmstadt. Here we report on ${}^{213}$Fr half-life determination [${T}_{1/2}$(${}^{213}$Fr) = 34.14$\phantom{\rule{0.16em}{0ex}}\ifmmode\pm\else\textpm\fi{}\phantom{\rule{0.16em}{0ex}}$0.06 s] at INFN-LNS, detailing the measurement protocol used. Direct comparison with the accepted value in the literature shows a discrepancy of more than three sigma. We propose this new value as a reference, discussing previous experiments.

On the Accuracy of a One-Compartment Approach for Determination of Drug Terminal Half-Life

The drug terminal half-life (t(1/2)) is commonly predicted by a simplified one-compartment approach (t(1/2) = ln 2V(ss)/CL), where V(ss) and CL are the steady-state volume of distribution and the total body clearance of drug, respectively. The analysis of the accuracy of this approach is provided. It turns out that most often a simplified one-compartment calculation underestimates t(1/2) by no more than 25% for human, 26% for dog, 20% for monkey, 19% for rat, and 23% for mouse. Thus, the application of a one-compartment calculation of t(1/2) is well justifiable, except for the rare cases of very high drug clearance (CL/(rQ) ≳ 0.5), where r is the equilibrium blood-plasma concentration ratio, and Q is the cardiac output.

Quantification of 60Fe atoms by MC-ICP-MS for the redetermination of the half-life

In many scientific fields, the half-life of radionuclides plays an important role. The accurate knowledge of this parameter has direct impact on, e.g., age determination of archeological artifacts and of the elemental synthesis in the universe. In order to derive the half-life of a long-lived radionuclide, the activity and the absolute number of atoms have to be analyzed. Whereas conventional radiation measurement methods are typically applied for activity determinations, the latter can be determined with high accuracy by mass spectrometric techniques. Over the past years, the half-lives of several radionuclides have been specified by means of multiple-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) complementary to the earlier reported values mainly derived by accelerator mass spectrometry. The present paper discusses all critical aspects (amount of material, radiochemical sample preparation, interference correction, isotope dilution mass spectrometry, calculation of measurement uncertainty) for a precise analysis of the number of atoms by MC-ICP-MS exemplified for the recently published half-life determination of 60Fe (Rugel et al, Phys Rev Lett 103:072502, 2009).

Half-life determination for short-lived radioisotopes 52V, 66Cu and 28Al

In this work, the half lives of 52V, 66Cu and 28Al were measured using a non-paralyzable dead-time correction to the regular exponential decay. For 28Al, a physical dead-time correction was also employed to allow a verification of the mathematical correction used. The resulting values were 3.734(3)min for 52V and 5.061(6)min for 66Cu; as for 28Al, the results were 2.233(9) min using the non-paralyzable correction and 2.228(5)min using the secondary correction, thus validating the mathematical approach.

High Diagnostic Utility of Second-Day Factor VIII Levels to Assess Pediatric Hemophilia A Pharmacokinetics

AbstractAbstract 3368 Background:The role of pharmacokinetic (PK) assessment of factor VIII (fVIII) plasma levels in hemophilia A patients (pts) is evolving. For two decades at our center and many others, full or “modified” PK studies were based on multiple levels drawn before and for several hours following infusion. This required IV access for frequent sampling as well as substantial staff, patient, and parent time. A practical consequence was that PK assessment was reserved for pts with concern for poor factor survival. Recently Björkman, Collins et al reported use of population-based PK sampling to obtain accurate half-life (t1/2) determination by limited blood sampling (2 levels only, 12–36 hours post dose, “Day 2”) in adults with hemophilia A [Haemophilia 16:597, 2010]. The aim of this study was to evaluate the applicability and practical use of these principles in a large pediatric hemophilia clinic, with a long-term goal of individualizing factor VIII dosing. Methods:For this IRB-approved chart review, 27 pts were identified through Hemophilia Center records and a hospital EMR search strategy, who had fVIII PK studies since 2002 at Boston Children’s Hospital. Four of 27 had an inhibitor at the time of assessment and were excluded from analysis. Maximum post-infusion fVIII concentrations (Cmax) were estimated from the TCI Works Program [Björkman, Haemophilia 17:e239, 2011]. Graphical and statistical analyses were conducted in GraphPad Prism 5.01. Graphical models in Prism used non-linear least squares fit to a one phase exponential decay curve with the “terminal plateau” parameter arbitrarily constrained to 0.5% (0.005U/ml fVIII) for severe hemophilia A. Results:Forty sets of PK studies were analyzed from 23 pts, median age 7.9 years, and including 8/23 patients (35%) with former inhibitors. The median z-score for BMI was +0.3; obesity was rare. All FDA approved recombinant fVIII brands were represented. The average t1/2 of fVIII in our pts was 6.8 ± 2.1 hours. 52% (12/23) of patients had PK values only within the first 8 hours after an infusion (plus pre-infusion “trough”). Eight non-inhibitor pts contributed multiple sets of PK to the study, over a maximum time interval of 8 years, with negligible variability over time. Due to the commonly observed rapid early fVIII clearance (“biphasic kinetics”), estimates of t1/2 based on Day 2 time points (after 12–24 h when available) are longer than estimates based on points within the first several hrs post infusion (“Day 1”) for pts in which both “Days” were available. Figure A demonstrates this effect in one pt, and shows t1/2 estimated from early vs. late samples. An example of Day 2 sampling alone is shown in Figure B. Conclusions:Second-day fVIII sampling shows promise in pediatric hemophilia A pts as published for adult pts. Testing our entire prophylaxis population by this method has significant implications for individualized vs. fixed dose prophylactic dosing strategies. In non-inhibitor pts, our center has historically used every-other-day prophylactic fVIII dosing at 25 U/kg usually not modified for individual PK. The recognition that Day 2 sampling is equal or superior to detailed first-day testing could result in manifold improvements in (a) pt satisfaction; (b) ability to test all prophylaxis pts rather than those with perceived bleeding risk; (c) ability to individualize treatment models based on PK assessments; (d) reduced testing cost per pt; and (e) potential large savings on a population basis for factor utilization. Individualized dose tailoring and kinetic analyses offer the potential for better pt health and decreased cost of hemophilia treatment. [Display omitted] Disclosures:Saxena:Bayer: Research Funding; Novo Nordisk: Research Funding. Neufeld:Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Bayer: DSMB membership, DSMB membership Other; Baxter: Research Funding.

Precision half-life determination of a mirror β transition: The decay of 31S

The half-life of the mirror \(\beta\) decay of 31S has been measured at the IGISOL facility at the University of Jyvaskyla. The value obtained is \(T_{1/2}(^{31}S)=(2553.4\pm 1.8)\) ms, in agreement with previous measurements, but with a precision that is better by a factor of ten than the literature value previously adopted. When the new result is combined with the QEC value measured recently at JYFLTRAP, a precision of better than \(10^{-3}\) is obtained for the ft value.

Precision measurement of the6He half-life and the weak axial current in nuclei

Studies of 6He beta decay along with tritium can play an important role in testing ab initio nuclear wave-function calculations and may allow for fixing low-energy constants in effective-field theories. Here, we present an improved determination of the 6He half-life to a relative precision of 3×10(-4). Our value of 806.89±0.11(stat)(-0.19syst)(+0.23) ms resolves a major discrepancy between previous measurements. Calculating the statistical rate function we determined the ft value to be 803.04(-0.23)(+0.26) s. The extracted Gamow-Teller matrix element agrees within a few percent with ab initio calculations.

Determination of rate constants and half-lives for the simultaneous biodegradation of several cyanobacterial metabolites in Australian source waters

The fate of five cyanobacterial metabolites was assessed in water sourced from Lake Burragorang (Warragamba Dam) in New South Wales, Australia. All of the studied metabolites were shown to be biodegradable in this water source. For some metabolites, biodegradation was influenced by factors, including temperature, location (within the water body) and seasonal variations. The biodegradation of the metabolites was shown to follow pseudo-first-order kinetics with rate constants ranging from 8.0 × 10−4 to 1.3 × 10−2 h−1. Half-lives of the metabolites were also estimated and ranged from 2.2 to 36.1 d. The order of ease of biodegradability in this water source followed the trend: microcystin-LR ≥ cylindrospermopsin > saxitoxins > geosmin ≥ 2-methylisoborneol. The lack of detection of the mlrA gene during microcystin biodegradation suggests that these toxins may be degraded via a different pathway. While no metabolite-degrading organisms were isolated in this study, the inoculation of previously isolated geosmin- and microcystin-degrading bacteria into Lake Burragorang water resulted in efficient biodegradation of the respective metabolites. For example, microcystin-degrading isolate TT25 was able to degrade three microcystin variants to concentrations below analytical detection within 24 h, suggesting that inoculation of such bacteria has the potential to enhance biodegradation in Lake Burragorang.

High-Precision Measurement of theNe19Half-Life and Implications for Right-Handed Weak Currents

We report a precise determination of the (19)Ne half-life to be T(1/2)=17.262±0.007 s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current standard model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.