Radioactive Half-life Research Articles

Two-proton radioactivity within Coulomb and proximity potential model * *Supported by the National Natural Science Foundation of China (12175100, 11975132), the Construct Program of the Key Discipline in Hunan Province, the Research Foundation of Education Bureau of Hunan Province, China (18A237), the Natural Science Foundation of Hunan Province, China (2015JJ3103, 2018JJ2321), the Innovation Group of Nuclear and Particle Physics in

Considering the preformation probability of the two emitted protons in the parent nucleus, we extend the Coulomb and proximity potential model (CPPM) to systematically study two-proton (2p) radioactivity half-lives of the nuclei close to proton drip line. The proximity potential chosen is Prox. 81 proposed by Blocki et al. in 1981. Furthermore, we apply this model to predict the half-lives of possible 2p radioactive candidates whose 2p radioactivity is energetically allowed or observed but not yet quantified in the evaluated nuclear properties table NUBASE2016. The predicted results are in good agreement with those from other theoretical models and empirical formulas, namely the effective liquid drop model (ELDM), generalized liquid drop model (GLDM), Gamow-like model, Sreeja formula and Liu formula.

Systematic study of laser-assisted proton radioactivity from deformed nuclei

In the present work, we systematically study the effect of ultra-intense laser fields on proton radioactivity of deformed proton emitters with the state-of-the-art Gaussian laser and the latest evaluated nuclear properties table. The calculated results indicate that ultra-intense laser fields affect the proton radioactivity half-life by changing the proton radioactivity penetration probability to some small but finite extent, and the $^{108}\mathrm{I}$ is the most sensitive parent nuclei to the strong laser pulse. Moreover, we found that the released energy of proton radioactivity is negatively related to the rate of change of the proton radioactivity penetration probability. Finally, we investigate the effect of the asymmetric chirp-laser pulse on the average rate of change in proton radioactivity penetration probability. It is shown that the rational use of positive chirp is equivalent to increasing the laser intensity by two orders of magnitude.

Validation of a System xc– Functional Assay in Cultured Astrocytes and Nervous Tissue Samples

Disruption of the glutamatergic homeostasis is commonly observed in neurological diseases and has been frequently correlated with the altered expression and/or function of astrocytic high-affinity glutamate transporters. There is, however, a growing interest for the role of the cystine-glutamate exchanger system xc– in controlling glutamate transmission. This exchanger is predominantly expressed in glial cells, especially in microglia and astrocytes, and its dysregulation has been documented in diverse neurological conditions. While most studies have focused on measuring the expression of its specific subunit xCT by RT-qPCR or by Western blotting, the activity of this exchanger in tissue samples remains poorly examined. Indeed, the reported use of sulfur- and carbon-radiolabeled cystine in uptake assays shows several drawbacks related to its short radioactive half-life and its relatively high cost. We here report on the elaborate validation of a method using tritiated glutamate as a substrate for the reversed transport mediated by system xc–. The uptake assay was validated in primary cultured astrocytes, in transfected cells as well as in crude synaptosomes obtained from fresh nervous tissue samples. Working in buffers containing defined concentrations of Na+, allowed us to differentiate the glutamate uptake supported by system xc– or by high-affinity glutamate transporters, as confirmed by using selective pharmacological inhibitors. The specificity was further demonstrated in primary astrocyte cultures from transgenic mice lacking xCT or in cell lines where xCT expression was genetically induced or reduced. As such, this assay appears to be a robust and cost-efficient solution to investigate the activity of this exchanger in physiological and pathological conditions. It also provides a reliable tool for the screening and characterization of new system xc– inhibitors which have been frequently cited as valuable drugs for nervous disorders and cancer.

Radiolabeling of PSMA-617 with 89Zr: A novel use of DMSO to improve radiochemical yield and preliminary small-animal PET results

IntroductionNovel diagnostic and therapeutic options are urgently needed for patients with metastatic castration-resistant prostate cancer (CRPC). PSMA-617 is one of the most promising ligands that bind to prostate specific membrane antigen (PSMA), the cell surface biomarker of CRPC. Of the radiolabeled PSMA ligands developed to date, [68Ga]Ga-PSMA-617 is most commonly used for PSMA positron emission tomography (PET) prior to radioligand therapy (RLT) with [177Lu]Lu-PSMA-617. However, the presence of 68Ga radioactivity (half-life 68 m) in urine at the early PET imaging time point complicates optimization of the therapeutic dose of PSMA-617 labeled with 177Lu (half-life 6.7 d). Thus, PET imaging with the long-lived positron emitter 89Zr (half-life 3.3 d) would be better suited in order to optimize the dose of [177Lu]Lu-PSMA-617 as 89Zr PET allows scans after excretion of the radioactive urine. Until now, PSMA-617 could not be radiolabeled with 89Zr with high radiochemical yield due to poor incorporation of 89Zr into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Here we report a novel method for radiolabeling PSMA-617 with 89Zr and the preliminary results of small-animal PET with [89Zr]Zr-PSMA-617. MethodsWe labeled PSMA-617 with 89Zr in a 1:1 mixture of DMSO and HEPES buffer at 90 °C for 30 min, followed by quality control analysis by HPLC. We then determined the dissociation constant (Kd) and logD values of [89Zr]Zr-PSMA-617. We obtained PET images of [89Zr]Zr-PSMA-617 at 24 h in mice bearing both LNCaP (PSMA-positive) and PC-3 (PSMA-negative) tumors (N = 5). The ex vivo [89Zr]Zr-PSMA-617 biodistribution was then examined separately using tissue samples of LNCaP-bearing mice at 2 h (N = 4) and 24 h (N = 4). Results[89Zr]Zr-PSMA-617 was prepared with a radiochemical yield of 70 ± 9%. The Kd value was 6.8 ± 3.5 nM. The logD value was −4.05 ± 0.20. PET images showed the highest uptake in LNCaP tumors (maximum standardized uptake value, SUVmax = 0.98 ± 0.32) and low uptake in kidneys (SUVmax = 0.18 ± 0.7) due to the absence of urine radioactivity. Conclusion[89Zr]Zr-PSMA-617 was successfully prepared using DMSO and HEPES buffer. [89Zr]Zr-PSMA-617 visualized PSMA-positive LNCaP tumors in the absence of radioactive urine 24 h p.i. Advances in knowledge and implications for patient careThis method of radiolabeling PSMA-617 with 89Zr using DMSO would be suitable for future clinical trials. Prediction of radiation dose by using [89Zr]Zr-PSMA-617 leads to the safe and effective RLT with [177Lu]Lu-PSMA-617.

Theoretical studies on two-proton radioactivity

The Coulomb and proximity potential model for deformed nuclei (CPPMDN) have been used to compute half-lives of two-proton ($2p$) radioactivity of $^{6}\mathrm{Be}$, $^{12}\mathrm{O}$, $^{16}\mathrm{Ne}$, $^{19}\mathrm{Mg}$, $^{45}\mathrm{Fe}$, $^{48}\mathrm{Ni}$, $^{54}\mathrm{Zn}$, and $^{67}\mathrm{Kr}$, and the values are compared with the experimental data. The predicted half-life values are also compared with six theoretical models and two empirical formulas. The standard deviation is least for the model CPPMDN ($\ensuremath{\sigma}=1.03$), compared to other theoretical models and formulas, which indicates that CPPMDN is the apt model for studying $2p$ radioactivity. I extended the model to predict half-lives of other 15 even-Z nuclei for which $2p$ radioactivity is energetically possible with released energy, ${Q}_{2p}>0$, and hope that the predictions may serve as a guide for future experimental investigations. The observed linear nature of the new Geiger-Nuttall plot of ${log}_{10}[{T}_{1/2}(s)]$ computed using CPPMDN versus $({Z}_{d}^{0.8}{\ensuremath{\ell}}^{0.25}){Q}_{2p}^{\ensuremath{-}1/2}$, stresses the reliability of the model in predicting $2p$ radioactivity half-lives.

Pharmacokinetics, Mass Balance, and Metabolism of the Novel Urate Transporter 1 Inhibitor [14C]HR011303 in Humans: Metabolism Is Mediated Predominantly by UDP-Glucuronosyltransferase.

HR011303, a promising selective urate transporter 1 inhibitor, is currently being studied in a phase III clinical trial in China for the treatment of hyperuricemia and gout. In the current study, the pharmacokinetics, mass balance, and metabolism of HR011303 were examined in six healthy Chinese male subjects who received a single oral dose of 10 mg of [14C]HR011303 (80 µCi). The results showed that HR011303 was rapidly absorbed with a median time to reach C max of 1.50 hours postdose, and the arithmetic mean half-life of total radioactivity was approximately 24.2 hours in plasma. The mean blood-to-plasma radioactivity concentration ratio was 0.66, suggesting the preferential distribution of drug-related components in plasma. At 216 hours postdose, the mean cumulative excreted radioactivity was 91.75% of the dose, including 81.50% in urine and 10.26% in feces. Six metabolites were identified, and the parent drug HR011303 was the most abundant component in plasma and feces, but a minor component in urine. Glucuronidation of the carboxylic acid moiety of HR011303 was the primary metabolic pathway in humans, amounting to 69.63% of the dose (M5, 51.57% of the dose; M5/2, 18.06% of the dose) in the urine; however, it was not detected in plasma. UDP-glucuronosyltransferase (UGT) 2B7 was responsible for the formation of M5. Overall, after a single oral dose of 10 mg of [14C]HR011303 (80 µCi), HR011303 and its main metabolites were eliminated via renal excretion. The major metabolic pathway was carboxylic acid glucuronidation, which was catalyzed predominantly by UGT2B7. SIGNIFICANCE STATEMENT: This study determined the absorption and disposition of HR011303, a selective urate transporter (URAT) 1 inhibitor currently in development for the treatment of hyperuricemia and gout. This work helps to characterize the major metabolic pathways of new URAT inhibitors and identify the absorption and clearance mechanism.

Systematic study of cluster radioactivity half-lives based on a modified Gamow-like model

In this study, taking into account of the contribution of the centrifugal potential on half-life and the effect of electrostatic shielding, we modify the Gamow-like model proposed by Zdeb et al [2013 Phys. Rev. C 87, 024 308] to systematically investigate the cluster radioactivity half-lives of nuclei ranging from 221Fr to 238U. The calculated results can reproduce the experimental data well. Additionally, this modified Gamow-like model is applied to predict the half-lives of cluster radioactivity nuclei whose experimental half-lives have the lower limit. It is found that the predicted results are in good agreement with the ones obtained by using the Gamow-like model and a Viola-Seaborg type formula.

Proton radioactivity and α-decay of neutron-deficient nuclei

Proton radioactivity and α-decay half-lives of neutron-deficient nuclei have been systematically studied. The proton-nucleus interaction potential is developed by single folding the density distribution of the daughter nuclei with the effective M3Y-Paris nucleon-nucleon (NN) interaction. The penetrability is calculated with the Wentzel-Kramers-Brillouin approximation. The applicability of the universal decay law on the proton decay half-lives has been examined and a new set of parameters has been identified. The competition between α-decay and proton radioactivity of neutron-deficient nuclei has been investigated. The proton radioactivity is found to be the dominant mode of decay for nuclides located very close to the proton drip-line. The effect of using different microscopic proton and neutron density distributions on the half-lives for these two decay modes is studied. It is found that the calculated half-lives with the microscopic densities that obtained from the self-consistent Hartree–Fock-Bogoliubov method successfully reproduce the experimental data. The impact of nuclear deformation on the half-lives is investigated for these two decay modes. The influence of nonlocality through the finite-range exchange part of the NN interaction on the α-decay process is elucidated. Our theoretical calculations have been confirmed experimentally and satisfactory agreement has been achieved.

Two-proton radioactivity of ground and excited states within a unified fission model * *Supported by the National Natural Science Foundation of China (U1832120, 11675265), the Natural Science Foundation for Outstanding Young Scholars of Hebei Province of China (A2020210012, A2018210146), the Natural Science Foundation of Hebei Province of China (A2021210010), the Continuous Basic Scientific Research Project (WDJC-2019-13) and the Leading Innovation

A unified fission model is extended to study two-proton radioactivity of the ground states of nuclei, and a good agreement between the experimental and calculated half-lives is found. The two-proton radioactivity half-lives of the ground states of some probable candidates are predicted within this model by inputting the released energies taken from the AME2020 table. It is shown that the predictive accuracy of the half-lives is comparable to those of other models. Then, two-proton radioactivity of the excited states of 14O, 17,18Ne, 22Mg, 29S, and 94Ag is discussed within the unified fission model and two analytical formulas. It is found that the experimental half-lives of the excited states are reproduced better within the unified fission model. Furthermore, the two formulas are not suitable for the study of two-proton radioactivity of excited states because their physical appearance deviates from the mechanism of quantum tunneling, and the parameters involved are obtained without including experimental data from the excited states.

Systematic study of two-proton radioactivity half-lives using the two-potential and Skyrme-Hartree-Fock approaches * *Supported in part by the National Natural Science Foundation of China (11205083, 11505100, 11705055), the Construct Program of the Key Discipline in Hunan Province, the Research Foundation of Education Bureau of Hunan Province, China (18A237), the Natural Science Foundation of Hunan Province, China (2018JJ2321), the Innovation Group

In this work, we systematically study the two-proton ( ) radioactivity half-lives using the two-potential approach, and the nuclear potential is obtained using the Skyrme-Hartree-Fock approach and the Skyrme effective interaction of SLy8. For true radioactivity ( 0 and 0, where and are the released energies of the one-proton and two-proton radioactivity, respectively), the standard deviation between the experimental half-lives and our theoretical calculations is 0.701. In addition, we extend this model to predict the half-lives of 15 possible radioactivity candidates with 0 obtained from the evaluated atomic mass table AME2016. The calculated results indicate a clear linear relationship between the logarithmic radioactivity half-lives ( ) and coulomb parameters [( + ) ] considering the effect of orbital angular momentum proposed by Liu [Chin. Phys. C 45, 024108 (2021)]. For comparison, the generalized liquid drop model (GLDM), effective liquid drop model (ELDM), and Gamow-like model are also used. Our predicted results are consistent with those obtained using other relevant models.

Cluster approach to spontaneous fission of even-even isotopes of U, Pu, Cm, Cf, Fm, No, Rf, Sg, and Hs

For even isotopes of nuclei U, Pu, Cm, Cf, Fm, No, Rf, Sg, and Hs, spontaneous fission and $\ensuremath{\alpha}$-decay half-lives are calculated within the dinuclear system model and compared with existing experimental data. Cluster radioactivity half-lives are also described for even U, Pu, and Cm isotopes. All these processes are considered for the evolution of a nucleus in the charge (mass) asymmetry coordinate and in the relative distance between the centers of clusters formed. The important roles of the driving potential and mass parameter in the charge asymmetry coordinate are shown for spontaneous fission. The global isotopic trends of spontaneous fission and $\ensuremath{\alpha}$-decay half-lives are studied. Drastic changes in the functional dependence of spontaneous fission half-life on the neutron number and in the absolute values of half-lives in the U--No and Rf--Hs nuclear groups are explained.

Systematic study of two-proton radioactivity with a screened electrostatic barrier * *Supported in part by the National Natural Science Foundation of China (11205083, 11505100, 11705055), the Construct Program of the Key Discipline in Hunan Province, the Research Foundation of Education Bureau of Hunan Province, China (18A237), the Natural Science Foundation of Hunan Province, China (2018JJ3324), the Innovation Group of Nuclear

In this study, a phenomenological model is proposed based on Wentzel-Kramers-Brillouin (WKB) theory and applied to investigate the two-proton ( ) radioactive half-lives of nuclei near or beyond the proton drip line. The total diproton-daughter nucleus interaction potential is composed of the Hulthen-type electrostatic term and the centrifugal term. The calculated radioactive half-lives can accurately reproduce the existing 10 experimental datasets of five true radioactive nuclei with σ = 0.736. In addition, we extend this model to predict the half-lives of possible radioactive nuclei whose radioactivity is energetically allowed or observed but not yet quantified in NUBASE2016. The predicted results are in agreement with those obtained using the Gamow-like model, generalized liquid drop model, Sreeja formula, and Liu formula.

Systematic study of two-proton radioactivity half-lives based on a modified Gamow-like model

In this work, we systematically study the two-proton ([Formula: see text]) radioactivity half-lives of nuclei close to the proton drip line within a modified Gamow-like model. Using this model, the calculated [Formula: see text] radioactivity half-lives can well reproduce the experimental data. Moreover, we blackuse this model to predict the [Formula: see text] radioactivity half-lives of 22 candidates blackwhose [Formula: see text] radioactivity is energetically allowed or observed but not yet quantized in evaluated nuclear properties table NUBASE2016. blackThe predicted results are in good agreement with the ones obtained by using Gamow-like model, effective liquid drop model (ELDM), generalized liquid drop model (GLDM) as well as a four-parameter formula.

Bisindole [3]arenes—Indolyl Macrocyclic Arenes Having Significant Iodine Capture Capacity

Bisindole [3]arenes—Indolyl Macrocyclic Arenes Having Significant Iodine Capture Capacity

Excretion and Distribution of the 60-kDa PEG Moiety Used in BAY 94-9027 in Male Wistar Rats

Introduction: PEGylation is a widely used method to prolong the half-life of therapeutic proteins. Long-acting factor VIII (FVIII) products developed through PEGylation may potentially reduce the burden associated with prophylaxis in patients with hemophilia A. BAY 94-9027 is a prolonged-half-life FVIII product modified through site-specific addition of a 60-kDa (2 × 30-kDa branched) PEG via a maleimide linker to a cysteine amino acid. BAY 1025662 is the 60-kDa PEG moiety used for PEGylation including linker and cysteine (PEG-60-Mal-Cys). In toxicology studies, BAY 94-9027 and BAY 1025662 were not associated with any adverse events or PEG-related cellular vacuolation (Ivens et al. Haemophilia. 2013;19:11-20). The rate-limiting clearance of the PEG part of PEGylated proteins after metabolism is expected to be similar to that when the corresponding PEG is administered alone (Baumann et al. Drug Discov Today . 2014;19:1623-1631). The study objective was to investigate the pharmacokinetics and mass balance of total radioactivity in male Wistar rats after a single intravenous (IV) administration of [14C]-labeled BAY 1025662, including size exclusion chromatography profiles of urine at selected time points.Methods: Radiolabeled BAY 1025662 ([prop-14C]BAY 1025662) was synthesized using a 2-step process resulting in a maleimide linker bearing the [14C] label at the propionic acid moiety. Radioactivity following a single IV dose of 11 mg/kg (the estimated maximal human PEG dose over ~30 years' treatment with BAY 94-9027) was determined in body fluids, organs and tissues, and in excreta by liquid scintillation counting after appropriate sample preparation and by quantitative whole-body autoradiography during and at the end of the study.Results: Single-dose mass balance studies using [prop-14C]BAY 1025662 showed that 30.4% of administered radioactivity was excreted within 1 week (23.7% in urine and 6.3% in feces); cumulative excretion at day 168 via urine and feces was 82.6% of the administered dose (68.4% via urine, 13.8% via feces). High-performance liquid chromatography profiling analysis of rat urine suggested that BAY 1025662 is excreted nearly unchanged (74% of total radioactivity, corresponding to 17.6% of dose, present unchanged in urine in the 0- to 168-hour interval). Radioactivity was continuously, albeit slowly, eliminated throughout the study; elimination half-life was 23 and 24 days in blood and plasma, respectively. The corresponding elimination half-lives of radioactivity were 33, 31, 39, 54, and 68 days in the liver, skin, carcass, testes, and kidneys, respectively. Elimination was almost complete at the end of experiment, with a total recovery of radioactivity (cumulative excretion plus residues in animals) of 89% on day 168. Following [prop-14C]BAY 1025662 administration, radioactivity was slowly distributed from blood to peripheral organs, reaching maximum concentration 2 hours postdose; highest maximum concentration was observed in blood, followed by lung and liver. At day 168, only ~4% of the administered radioactive dose was still present in the animal body, partially localized in endocrine/exocrine glands and lymphatic organs. No residual radioactivity was observed in the brain, indicating no crossing of the blood-brain barrier.Conclusions: Following single-dose administration of [prop-14C]BAY 1025662, elimination was almost complete by the end of the experiment on day 168. These results suggest that there are excretion processes in place for high-molecular-weight PEGs such as the PEG 60 moiety used in BAY 94-9027. Two clearance processes are proposed for large PEGs (>30 kDa), as indicated by a faster initial excretion over the first 1-2 weeks, followed by a nonspecific uptake into cells by pinocytosis leading to a longer elimination half-life. The PEG moiety can be recycled from inside the cells back to the plasma, possibly by exocytosis, to then undergo further (mainly renal) excretion (Baumann et al. Drug Discov Today . 2014;19:1623-1631). DisclosuresBaumann:Bayer AG: Employment. Schwarz:Bayer AG: Employment. Hucke:Bayer AG: Employment. Piel:Bayer AG: Employment. Sandmann:Bayer AG: Employment.

Two-proton radioactivity of exotic nuclei beyond proton drip-line

To search for new candidates of the true and simultaneous two-proton (2p) radioactivity, the 2p decay energies (Q 2p ) are extracted by the Weizsäcker–Skyrme-4 (WS4) model, the finite-range droplet model (FRDM), the Koura–Tachibana–Uno–Yamada (KTUY) model and the Hartree–Fock–Bogoliubov mean-field model with the BSk29 Skyrme interaction (HFB29). Then, the 2p radioactivity half-lives are calculated within the generalized liquid drop model by inputting the four types of Q 2p values. By the energy and half-life constraints, it is found that the probable 2p decay candidates are the nuclei beyond the proton-drip line in the region of Z ≤ 50 based on the WS4 and KTUY mass models. For the FRDM mass model, the probable 2p decay candidates are found in the region of Z ≤ 44. However, the 2p-decaying candidates are predicted in the region of Z ≤ 58 by the HFB29 mass model. It means that the probable 2p decay candidates of Z > 50 are only predicted by the HFB29 mass model. Finally, the competition between the true 2p radioactivity and α-decay for the nuclei above the N = Z = 50 shell closures is discussed. It is shown that 101Te, 111Ba and 114Ce prefer to 2p radioactivity and the dominant decay mode of 107Xe and 116Ce is α-decay.

Proton radioactivity within the generalized liquid drop model with various versions of proximity potentials

In the present work, we systematically investigate the proton radioactivity half-lives of spherical proton emitters adopting a generalized liquid drop model (GLDM) with 16 different proximity potentials, of which the proximity potential Prox.77-13 gives the closest results to the experimental data. Combined with the previous conclusion that the GLDM with proximity potential Prox.77-13 can also best describe α decay half-lives, which makes the model more uniform and consistent. Further, we use the proximity potential Prox.77-13 in GLDM to predict the proton radioactivity half-lives of 14 spherical proton emitters that are allowed energetically but not yet observed experimentally or specifically quantified. Finally, we research the Geiger−Nuttall law for proton radioactivity. The results reveal that the Geiger−Nuttall law can also be well used to study the proton radioactivity half-lives of isotopes with the same orbital angular momentum l.

Imaging Somatostatin Positive Tumors with Tyr3-Octreotate/Octreotide Conjugated to Desferrioxamine B Squaramide Radiolabeled with either Zirconium-89 or Gallium-68.

Radiolabeled derivatives of Tyr3-octreotide and Tyr3-octreotate, synthetic analogues of the peptide hormone somatostatin, can be used for positron emission tomography (PET) imaging of somatostatin receptor expression in neuroendocrine tumors. In this work, a squaramide ester derivative of desferrioxamine B (H3DFOSq) was used attach either Tyr3-octreotide or Tyr3-octreotate to the metal binding ligand to give H3DFOSq-TIDE and H3DFOSq-TATE. These new peptide-H3DFOSq conjugates form stable complexes with either of the positron-emitting radionuclides gallium-68 (t1/2 = 68 min) or zirconium-89 (t1/2 = 3.3 days). The new complexes were evaluated in an AR42J xenograft model that has endogenous expression of SSTR2. All four agents displayed good tumor uptake and produced high-quality PET images. For both radionuclides, the complexes formed with H3DFOSq-TATE performed better, with higher tumor uptake and retention than the complexes formed with H3DFOSq-TIDE. The versatile ligands presented here can be radiolabeled with either gallium-68 or zirconium-89 at room temperature. The long radioactive half-life of zirconium-89 makes distribution of pre-synthesized tracers produced to certified standards feasible and could increase the number of clinical centers that can perform diagnostic PET imaging of neuroendocrine tumors.

Bomb 137Cs in modern honey reveals a regional soil control on pollutant cycling by plants

137Cs is a long-lived (30-year radioactive half-life) fission product dispersed globally by mid-20th century atmospheric nuclear weapons testing. Here we show that vegetation thousands of kilometers from testing sites continues to cycle 137Cs because it mimics potassium, and consequently, bees magnify this radionuclide in honey. There were no atmospheric weapons tests in the eastern United States, but most honey here has detectable 137Cs at >0.03 Bq kg−1, and in the southeastern U.S., activities can be >500 times higher. By measuring honey, we show regional patterns in the biogeochemical cycling of 137Cs and conclude that plants and animals receive disproportionally high exposure to ionizing radiation from 137Cs in low potassium soils. In several cases, the presence of 137Cs more than doubled the ionizing radiation from gamma and x-rays in the honey, indicating that despite its radioactive half-life, the environmental legacy of regional 137Cs pollution can persist for more than six decades.

Predictability of Elimination and Excretion of Small Molecules in Animals and Humans, and its Impact on Dosimetry for human ADME Studies with Radiolabeled Drugs.

We assessed the extent to which urinary and fecal excretion of 14C-labeled drug material in animal ADME studies was predictive of human ADME studies. We compared observed plasma elimination half-lives for total drug-related radioactivity in humans to pre-study predictions, and we estimated the impact of any major differences on human dosimetry calculations. We included 34 human ADME studies with doses of 14C above 0.1 MBq. We calculated ratios of dosimetry input parameters (percentage fecal excretion in humans versus animals; observed half-life in humans versus predicted pre-study) and output parameters (effective dose post-study versus pre-study) and assessed their relationship. A quantitative correlation assessment did not show a statistically significant correlation between the ratios of percentages of 14C excreted in feces and the ratios of dosimetry outcomes in the entire dataset, but a statistically significant correlation was found when assessing the studies that were based on ICRP 60/62 (n=19 studies; P=0.0028). There also appeared to be a correlation between the plasma half-life ratios and the ratios of dosimetry results. A quantitative correlation assessment showed that there was a statistically significant correlation between these ratios (P<0.0001). In all cases where the plasma elimination half-life for 14C in humans was found to be longer than the predicted value, the radiation burden was still within ICRP Category IIa. Containment of the actual radiation burden below the limit of 1.00 mSv appeared to be determined partly also by our choice to limit 14C doses to 3.7 MBq.