Improved detection and measurement of low levels of [18F]fluoride metabolized from [18F]-labeled pyrimidine nucleoside analogues in biological samples

IntroductionIt is important to identify all circulating metabolites, including free fluoride, for accurate pharmacokinetic modeling of [¹⁸F]-labeled radiotracers. We sought to determine the most efficient method to detect and quantify low levels of free [¹⁸F]fluoride in biological samples.MethodsLow levels of [¹⁸F]fluoride were analyzed using two methods: (A) an ion-exchange cartridge and gamma counting, and (B) radio-HPLC, to compare the detection limits of these two analytical methods. Twenty microliters of [¹⁸F]fluoride solution was loaded onto an ion-exchange cartridge, then eluted with 20% MeCN/water (5 ml) and radioactivity trapped in the cartridge counted on a gamma counter. [¹⁸F]Fluoride was also determined in plasma and urine from mice injected with [¹⁸F]-labeled thymidine analogues using Method A.ResultsThe detection sensitivity of Method A was 9.4-fold higher than that of Method B (0.075±0.004 vs. 0.71±0.02 nCi). With Method A, [¹⁸F]fluoride was determined in plasma for [¹⁸F]FLT, [¹⁸F]FMAU, [¹⁸F]FEAU and N³-[¹⁸F]FPrT as 1.4±0.31% (n=4), 0.17±0.49% (n=3), 4.88±1.62% (n=3) and 12.94±0.48% (n=4), respectively. The amount of [¹⁸F]fluoride determined in the urine was 11.49±1.60% (n=4) from [¹⁸F]FLT, 5.36±2.34% (n=3) from [¹⁸F]FMAU, 13.57±1.96% (n=3) from [¹⁸F]FEAU and 11.19±1.98% (n=4) from N³-[¹⁸F]FPrT.ConclusionLow levels of [¹⁸F]fluoride in biological samples can be detected and quantified using an ion-exchange cartridge and gamma counting. This methodology is simple, accurate and superior to the standard use of radio-HPLC on a C₁₈ column for metabolite analysis, and it should be useful in pharmacokinetic modeling for animal imaging studies using an [¹⁸F]-labeled radiotracer and PET.     

Evaluation of F-18-labeled 5-iodocytidine (18F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging

Objective

Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2′-deoxy-2′-[¹⁸F]fluoro-β-d-arabinofuranosyl)-5-iodocytosine (¹⁸F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2’-deoxy-2’-[¹⁸F]fluoro-5-iodo-1-β-D-arabinofuranosyluracil (¹⁸F-FIAU) and 2’-deoxy-2’-[¹⁸F]fluoro-5-ethyl-1-β-D-arabinofuranosyluracil(¹⁸F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model.

Methods

A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of ¹⁸F-FIAC, ¹⁸F-FIAU and ¹⁸F-FEAU were conducted to characterize the biological properties of these tracers.

Results

Highly specific uptake of ¹⁸F-FIAC, ¹⁸F-FIAU and ¹⁸F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(−) cellular uptake ratio after a 2-h incubation was 66.6±25.1, 76.3±18.2 and 247.2±37.2, respectively. In biodistribution studies, ¹⁸F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(−) tumor uptake ratio at 2 h postinjection) comparable with ¹⁸F-FIAU (15.8) but lower than ¹⁸F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor.

Conclusion

Our findings suggested that the cytidine analogue ¹⁸F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. ¹⁸F-FIAC may be regarded as the prodrug of ¹⁸F-FIAU in vivo.     

G-6A polymorphism of angiotensinogen gene modulates the effect of blood pressure on carotid intima-media thickness. The Bogalusa Heart Study

BACKGROUND: The adverse association between blood pressure and carotid artery intima-media thickness (IMT), a surrogate measure of subclinical atherosclerosis, is well-known. However, whether the G-6A polymorphism of the angiotensinogen (AGT) gene, a candidate gene of hypertension and vascular remodeling, modulates this relationship is unknown. METHODS: In 662 white and black subjects aged 25 to 43 years (73.4% white, 39.7% male), common carotid IMT was measured by B-mode ultrasonography. RESULTS: The variant A-6 allele frequency was higher in blacks than in whites (0.850 v 0.448, P < .0001). In a bivariate analysis, there were no differences in mean arterial blood pressure and common carotid IMT between carriers and noncarriers of the G allele in whites, blacks, or the total sample, after adjusting for gender, age, and race. In a multivariable regression analysis that included the status of the G allele (carriers versus noncarriers) along with gender, age, mean arterial blood pressure, body mass index, LDL cholesterol, triglycerides:HDL cholesterol ratio, homeostasis model assessment of insulin resistance, smoking, and race (in the total sample), mean arterial blood pressure was significantly and adversely associated with common carotid IMT in whites, blacks, and the total sample. This adverse positive relationship between mean arterial blood pressure and common carotid IMT was noted among noncarriers but not carriers of the G allele (comparison of slopes, P = .02) in the total sample. Although the interaction was not significant (P = .2 and P = .05 in whites and blacks, respectively), a trend similar to that in the total sample was found in both races. CONCLUSIONS: In a recessive manner, the genetic variant (G-6A) of the AGT gene modulates the association between blood pressure and carotid IMT in young adults.     

Fetal heart rate monitoring based on independent component analysis

In this paper, an algorithm based on independent component analysis (ICA) for extracting the fetal heart rate (FHR) from maternal abdominal electrodes is presented. Three abdominal ECG channels are used to extract the FHR in three steps: first preprocessing procedures such as DC cancellation and low-pass filtering are applied to remove noise. Then the algorithm for multiple unknown source extraction (AMUSE) algorithm is fed to extract the sources from the observation signals include fetal ECG (FECG). Finally, FHR is extracted from FECG. The method is shown to be capable of completely revealing FECG R-peaks from observation leads even with a SNR=-200dB using semi-synthetic data.     

Flocculant-disinfectant point-of-use water treatment for reducing arsenic exposure in rural Bangladesh

We introduced flocculant-disinfectant water treatment for 12 weeks in 103 households in Bangladesh to assess if drinking water would be chemically and microbiologically improved and the body burden of arsenic reduced. The median concentration of arsenic in tubewell water decreased by 88% after introduction of the flocculant-disinfectant from 136 μg/l at baseline to 16 (p < 0.001). The median concentration of total urinary arsenic decreased 42% from 385 μg/g creatinine at baseline to 225 μg/g creatinine after intervention (p < 0.001). Among 206 post-intervention drinking water samples that were reportedly treated on the date the sample was collected, 99 (48%) lacked residual free chlorine and 100 (49%) were contaminated with thermotolerant coliforms. The flocculant-disinfectant markedly reduced arsenic in drinking water, but treated drinking water was frequently contaminated with fecal organisms. The lesser reduction in urinary arsenic compared to water arsenic and the health consequences of this reduction require further research.     

Living on the Extreme Margin: Social Exclusion of the Transgender Population (Hijra) in Bangladesh

The transgender people (hijra), who claim to be neither male nor female, are socially excluded in Bangladesh. This paper describes social exclusion of hijra [The term is used in this abstract both in singular and plural sense] focusing on the pathway between exclusion and sexual health. In an ethnographic study, 50 in-depth interviews with hijra, 20 key-informant interviews, and 10 focus-group discussions (FGDs), along with extensive field observations, were conducted. The findings revealed that hijra are located at the extreme margin of exclusion having no sociopolitical space where a hijra can lead life of a human being with dignity. Their deprivations are grounded in non-recognition as a separate gendered human being beyond the male-female dichotomy. Being outside this norm has prevented them from positioning themselves in greater society with human potential and security. They are physically, verbally, and sexually abused. Extreme social exclusion diminishes self-esteem and sense of social responsibility. Before safer sex interventions can be effective in a broader scale, hijra need to be recognized as having a space on society''s gender continuum. Hijra, as the citizens of Bangladesh and part of society''s diversity, have gender, sexual and citizenship rights, that need to be protected.Key words: Hijra, HIV, Social exclusion, Bangladesh     

A new simple screening method for the diagnosis of medium chain acyl-CoA dehydrogenase deficiency

We describe a simple inexpensive method for the detection of octanoyl-carnitine in urine by reverse-phase high performance thin-layer chromatography of the p-bromophenacyl derivative. This method provides a rapid and reliable means for the diagnosis of medium-chain acyl-CoA dehydrogenase deficiency which is suitable for routine laboratory use.     

Thermal conductivity of polyurethane sheets containing beryllium oxide nanofibers

Polyvinyl alcohol/beryllium sulfate/polyethyleneimine (PVA/BeSO₄/PEI) precursor nanofibers (NFs) was first fabricated to obtain PVA/BeSO₄/PEI electrospun NFs by electrospinning technology, finally manufactured beryllium oxide (BeO) NFs followed by various heat treatment methods. The minimum calcination temperature for pure BeO NFs was 1000 °C, and the minimum specific surface area (5.1 m² g⁻¹) and pore volumes (0.0128 cm³ g⁻¹) were at 1300 °C. 46.18% Be and 53.82% O was measured in BeO NFs by X-ray photoelectron spectroscopy. BeO NFs were then impregnated with polyurethane (PU) aqueous solution to make PU/BeO NFs heat-dissipating sheet. This heat-dissipating sheet showed superior thermal conductivity (14.4 W m⁻¹ K⁻¹) at 41.4 vol% BeO NFs content. The electrical insulating properties of the heat-dissipating sheet were likewise excellent (1.6 × 10¹² Ω □⁻¹). In this study, the author attempted to create a thermally conductive but electrically insulating PU/BeO NFs heat-dissipating sheet that could effectively eliminate generated heat from electric equipment.

The BeO NFs’ elongated shape, which provides excellent heat pathways for the BeO NFs in the resin.