Dose-response relationship between toothpaste soluble fluoride absorbed in the gastrointestinal tract and saliva fluoride secretion

Aim: This study aimed to evaluate if there is a dose-response relationship between toothpaste chemically soluble fluoride absorbed in the gastrointestinal tract and fluoride secreted by saliva, giving support to the use of saliva as surrogate for plasma fluoride. Methods: A 4-phase single blind study was conducted, in which 10 participants were subjected in each phase to one of the assigned treatment groups: group I: fresh sample of a Na2FPO3/CaCO3-based toothpaste with 1,334 µg F/g of total soluble fluoride (TSF) and groups II­IV: aged samples of this toothpaste presenting TSF concentrations of 1,128, 808, and 687 µg F/g, respectively. In all phases, the participants ingested an amount of toothpaste equivalent to 70.0 µg F/Kg body weight, as total fluoride (TF). Saliva and blood samples were collected before (baseline) and up to 180 min after toothpaste ingestion as indicator of fluoride bioavailability. F concentration in saliva and blood plasma was determined with a fluoride ion-specific electrode. The areas under the curve (AUC) of F concentration versus time (AUC = ng F/mL × min) and the peaks of fluoride concentration (Cmax) in saliva and plasma were calculated. Results: A significant correlation between mg of TSF ingested and the AUC (r=0.47; p<0.01), and Cmax (r=0.59; p<0.01) in saliva was found; for TF, the correlation was not significant (p>0.05). In addition, the correlations between plasma and saliva fluoride concentrations were statistically significant for AUC (r=0.55; p<0.01) as for Cmax (r=0.68; p<0.01). Conclusion: The findings support that saliva can be used as a systemic biomarker of bioavailable fluoride present in Na2FPO3/CaCO3-based toothpaste

Fluoride release from two types of fluoride-containing orthodontic adhesives: Conventional versus resin-modified glass ionomer cements-An in vitro study.

INTRODUCTION: Development of white spot lesions (WSLs) during orthodontic treatment is a common risk factor. Fixation of the orthodontic appliances with glass ionomer cements could reduce the prevalence of WSL's due to their fluoride release capacities. The purpose of this study was to evaluate differences of fluoride release properties from resin-modified and conventional glass ionomer cements (GICs). METHODS: The resin-modified GICs Fuji ORTHO LC (GC Orthodontics), Meron Plus QM (VOCO), as well as the conventional GICs Fuji ORTHO (GC Orthodontics), Meron (VOCO) and Ketac Cem Easymix (3M ESPE) were tested in this study. The different types of GICs were applied to hydroxyapatite discs according to the manufacturer's instructions and stored in a solution of TISAB III (Total Ionic Strength Adjustment Buffer III) and fluoride-free water at 37°C. Fluoride measurements were made after 5 minutes, 2 hours, 24 hours, 14 days, 28 days, 2 months, 3 months and 6 months. One factor analysis of variance (ANOVA) was used for the overall comparison of the cumulative fluoride release (from measurement times of 5 minutes to 6 months) between the different materials with the overall level of significance set to 0.05. Tukey's post hoc test was used for post hoc pairwise comparisons in the cumulative fluoride release between the different materials. RESULTS: The cumulative fluoride release (mean ± sd) in descending order was: Fuji ORTHO LC (221.7 ± 10.29 ppm), Fuji ORTHO (191.5 ± 15.03 ppm), Meron Plus QM (173.0 ± 5.89 ppm), Meron (161.3 ± 7.84 ppm) and Ketac Cem Easymix (154.6 ± 6.09 ppm) within 6 months. Analysis of variance detected a significant difference in the cumulative fluoride release between at least two of the materials (rounded p-value < 0.001). Pairwise analysis with Tukey's post hoc test showed a significant difference in the cumulative fluoride release for all the comparisons except M and MPQM (p = 0.061) and KCE and M (p = 0.517). CONCLUSION: Fluoride ions were released cumulatively over the entire test period for all products. When comparing the two products from the same company (Fuji ORTHO LC vs. Fuji ORTHO from GC Orthodontics Europe GmbH and Meron Plus QM vs. Meron from VOCO GmbH, Mannheim, Germany), it can be said that the resin-modified GICs have a higher release than conventional GICs. The highest individual fluoride release of all GICs was at 24 hours. A general statement, whether resin-modified or conventional GICs have a higher release of fluoride cannot be made.

Synthesis of [18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics.

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, ß-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E's biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[18F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([18F]F-γ-T-3) was prepared for this purpose. [18F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [18F]fluoride in DMF/K222. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [18F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [18F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [18F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.

On the release of fluoride from biofilm reservoirs during a cariogenic challenge: an in situ study.

Biofilm fluoride reservoirs may be a source of fluoride to the fluid phase during a sugar challenge reducing tooth mineral loss. However, the evidence for that is conflicting and has not been studied in biofilms containing different fluoride levels. In order to test fluoride release from biofilms with distinct fluoride concentrations, biofilms were grown in situ exposed to a combination of placebo, calcium and fluoride rinses forming biofilms with no (fluoride-free rinses), low (fluoride-only rinses) or high (calcium followed by fluoride rinses) fluoride concentrations, and collected before and 5 min after a sucrose challenge. Rinsing with fluoride increased fluoride concentration in the biofilm (p < 0.05), mainly when a calcium pre-rinse was used before the fluoride (p < 0.05). However, after a sugar challenge, no significant increase in the biofilm fluid fluoride concentration was observed, even in the fluoride-rich biofilms (p > 0.05). Fluoride-rich biofilms do not release fluoride to the fluid phase during a sugar challenge.

A Janus upconverting nanoplatform with biodegradability for glutathione depletion, near-infrared light induced photodynamic therapy and accelerated excretion.

The major limitations of photodynamic therapy (PDT) are the poor tissue penetration of excitation light and the neutralization of reactive oxygen species (ROS) generated by overexpressed glutathione (GSH) in cancer cells. Despite tremendous efforts to design nanoplatforms, PDT still suffers from unsatisfactory effects. Furthermore, the residual of nanomaterials in the body has restricted their clinical application. To address these issues, Janus nanocomposites containing an Yb/Er codoped NaYF4 upconverting nanocrystal head and a disulfide-bridged mesoporous organosilicon body (UCN/MON) with loaded chlorin e6 (Ce6) were designed. On one hand, the upconverting nanocrystal head can convert near-infrared (NIR) light into visible light to activate Ce6 to release ROS. On the other hand, the silica body can be degraded though a redox reaction with GSH, to not only improve the tumor selectivity of the photosensitizer by redox- and pH-triggered Ce6 release, but also diminish the concentration of GSH in cancer cells to reduce the depletion of ROS. Thereby, an enhanced PDT triggered by NIR irradiation was achieved. Furthermore, UCN/MONs showed a higher clearance rate after therapeutic actions than nonbiodegradable UCN/MSNs due to their biocompatibility. Taken together, this work revealed the potential of UCN/MONs for highly efficient and NIR-induced PDT, highlighting the prospects of UCN/MONs in the clinic.

A randomised oral fluoride retention study comparing intra-oral kinetics of fluoride-containing dentifrices before and after dietary acid exposure.

OBJECTIVE: This exploratory, randomised, single-blind, crossover, study evaluated fluoride and calcium ion concentrations and pH following use of one of two 1450 ppm fluoride (NaF), 5% w/w KNO3 dentifrices: (1) test dentifrice (with cocamidopropyl betaine) with an orange juice (OJ) rinse; (2) test dentifrice with a deionized (DI) water rinse or (3) comparator dentifrice (with sodium lauryl sulphate and tetrasodium pyrophosphate) with an OJ rinse. DESIGN: Eighteen participants used their assigned dentifrice, rinsed with DI water, then expectorate was collected. Sixty min post-brushing, participants rinsed with OJ or DI water then expectorate was collected. Saliva samples were collected pre-brushing and at 1, 5, 10, 15, 30 and 60 min post-brushing and following the 60 min OJ/DI water rinse. The pH of samples was taken. RESULTS: Significant differences (p < 0.05) were found in salivary fluoride ion concentrations between test and comparator dentifrices at 30 and 60 min and following the 60 min OJ rinse, favouring the former. Significant differences were also found between test and comparator dentifrices for salivary calcium ion concentration at 1, 5 and 10 min (p < 0.0001), favouring the former, and between test or comparator + OJ rinse and test + water rinse (p < 0.005), favouring the latter. No pH differences were shown prior to OJ/water rinse. Products were generally well-tolerated. CONCLUSIONS: Results confirmed that acid-labile fluoride is released from the oral cavity following a dietary acid challenge and showed that formulation excipients may impact on retention of such.

The synergistic effects of SrF2 nanoparticles, YSZ nanoparticles, and poly-ε-l-lysin on physicomechanical, ion release, and antibacterial-cellular behavior of the flowable dental composites.

Resin-based pit-and-fissure sealants (flowable resin composites) were formulated using bisphenol-A-glycerolatedimethacrylate (Bis-GMA)-triethylene glycol dimethacrylate-(TEGDMA)-diurethanedimethacrylate (UDMA) mixed monomers and multiple fillers, including synthetic strontium fluoride (SrF2) nanoparticles as a fluoride-releasing and antibacterial agent, yttria-stabilized zirconia (YSZ) nanoparticles as an auxiliary filler, and poly-ε-l-lysin (ε-PL) as an auxiliary antibacterial agent. Based on the physical, mechanical and initial antibacterial properties, the formulated nano-sealant containing 5 wt% SrF2, 5 wt% YSZ and 0.5 wt% ε-PL was selected as the optimal specimen and examined for ion release and cytotoxicity. The results showed an average release rate of 0.87 µg·cm-2·day-1 in the aqueous medium (pH 6.9) and 1.58 µg·cm-2·day-1 in acidic medium (pH 4.0). The maximum cytotoxicity of 20% toward human bone marrow mesenchymal stem cells (hMSCs) was observed according to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) cytotoxicity assay and acridine orange staining test. A synergy between SrF2 nanoparticles and ε-PL exhibited a better antibacterial activity in terms of colony reduction compared to the other samples. However, the inclusion of SrF2 and ε-PL caused mechanically weakening of the sealants that was partly compensated by incorporation of YSZ nanoparticles (up to 10 wt%).

Environmental exposure of arsenic and fluoride and their combined toxicity: A recent update.

Environmental exposure to arsenic (As) and fluoride (F) in the recent year has been increased because of excessive use of naturally contaminated ground water. Surface water is also regularly contaminated with these elements in various industrial areas. Arsenicosis and fluorosis upon individual exposure of As and F are reported in many studies. A syndrome of endemic As poisoning and fluorosis occurs during concurrent exposure of As and F. Previous reports showed synergistic, antagonistic and independent effects of these two compounds, although few recent reports also revealed antagonistic effects after co-exposure. Interaction during intestinal absorption and influence of F on As metabolism might be the cause of antagonism. The synergism/antagonism is thought to depend on the dose and duration of the co-exposure. However, the detailed mechanism is still not fully understood and needs further studies. Removal technologies of As and F from contaminated water is available but removal of such contaminants from food is yet to be developed. Antioxidants are useful to mitigate the toxic effects of As and F. This review focused on the effect of co-exposure, amelioration as well as removal techniques of As and F.

Synthetic hydroxyapatite: a recruiting platform for biologically active molecules.

Background and purpose - Targeted delivery of drugs is important to achieve efficient local concentrations and reduce systemic side effects. We hypothesized that locally implanted synthetic hydroxyapatite (HA) particles can act as a recruiting moiety for systemically administered drugs, leading to targeted drug accretion.Methods - Synthetic HA particles were implanted ectopically in a muscle pouch in rats, and the binding of systemically circulating drugs such as zoledronic acid (ZA), tetracycline and 18F-fluoride (18F) was studied. The local biological effect was verified in an implant integration model in rats, wherein a hollow implant was filled with synthetic HA particles and the animals were given systemic ZA, 2-weeks post-implantation. The effect of HA particle size on drug binding and the possibility of reloading HA particles were also evaluated in the muscle pouch.Results - The systemically administered biomolecules (ZA, tetracycline and 18F) all sought the HA moiety placed in the muscle pouch. Statistically significant higher peri-implant bone volume and peak force were observed in the implant containing HA particles compared with the empty implant. After a single injection of ZA at 2 weeks, micro HA particles showed a tendency to accumulate more 14C-zoledronic acid (14C-ZA) than nano-HA particles in the muscle pouch. HA particles could be reloaded when ZA was given again at 4 weeks, showing increased 14C-ZA accretion by 73% in microparticles and 77% in nanoparticles.Interpretation - We describe a novel method of systemic drug loading resulting in targeted accretion in locally implanted particulate HA, thereby biologically activating the material.

Fluoride content in children's dentifrices marketed in Lima, Peru.

The aim of the present study was to determine the concentration of total fluoride (TF) and total soluble fluoride (TSF) in children's dentifrices marketed in the city of Lima, Peru. Three samples of 23 dentifrices (4 without fluoride and 19 with fluoride) were purchased in different pharmacies in Lima, Peru. The TF and TSF concentrations found in the dentifrices were determined by ion-selective electrode, expressed in ppm F (µg F/g of dentifrice). The TF concentration in the majority of the fluoride toothpastes matched that shown on the label, except for one declared as 1450 ppm F by the manufacturer, whereas only 515.1 ppm F was found. The concentration of TSF found in the fluoride toothpastes ranged from 457.5 to 1134.8 ppm F. All the dentifrices were formulated with silica, but one also presented calcium carbonate. In conclusion, 83% of the children's dentifrices marketed in Lima, Peru, were fluoridated, but only 53% contained a TSF concentration greater than 1000 ppm F, the minimum concentration required to provide an anticaries effect.

Differential fluoride uptake induces variable physiological damage in a non-aromatic and an aromatic indica rice cultivar.

The current study illustrates the systemic damages caused by increasing concentration of fluoride in non-aromatic rice variety, IR-64 and aromatic rice Gobindobhog (GB). Analysis of the physiological parameters like shoot length, root length and electrolyte leakage along with crucial damage indices like chlorophyll, malondialdehyde, H2O2 and protease activity indicated higher fluoride adaptation in GB compared to IR-64. IR-64 exhibited unregulated fluoride bioaccumulation when exposed to 25 mg L-1 NaF stress, whereas fluoride uptake in GB was much regulated. Gene expression studies proposed that CLC2 rather than CLC1 mediated the fluoride import. Fluoride also triggered higher P-H+/ATPase accumulation in GB compared to IR-64, thus highlighting efficient homeostasis in stressed GB. Unlike IR-64, GB could maintain photosynthesis (RuBisCo expression), sugar metabolism (α-amylase expression and activity), glycolysis and Krebs cycle even under high concentration of fluoride stress. Fluoride also inhibited nitrate reductase activity in both the cultivars. The present research illustrates differential phytotoxicity emerging out of fluoride accumulation in rice seedlings, highlighting that IR-64 is a highly susceptible variety, whereas GB exhibits physiological plasticity and is better adapted to higher concentrations of fluoride.

Long-term exposure to fluoride as a factor promoting changes in the expression and activity of cyclooxygenases (COX1 and COX2) in various rat brain structures.

BACKGROUND: Sixty percent of the mammalian brain is composed of lipids including arachidonic acid (AA). AA released from cell membranes is metabolised in the cyclooxygenase (COX) pathway to prostanoids - biologically active substances involved in the regulation of many processes including inflammation. It has been shown that long-term exposure to fluoride in pre and neonatal period is dangerous because this element is able to penetrate through the placenta and to cross the blood-brain barrier. Exposure to fluoride during the development affects metabolism and physiology of neurons and glia which results in the impairment of cognitive functions but the exact mechanisms of fluoride neurotoxicity are not clearly defined. OBJECTIVE: The aim of this study was to determine whether exposure to fluoride during the development affects COXes activity and the synthesis of prostanoids. MATERIAL AND METHODS: Pre- and postnatal toxicity model in Wistar rats was used. Experimental animals received 50 mg/L of NaF in drinking water ad libitum, while control animals received tap water. In cerebral cortex, hippocampus, cerebellum and striatum were measured fluoride concentration, COX1 and COX2 genes expression, immunolocalization of the enzymatic proteins and concentration of PGE2 and TXB2. RESULTS: of this study showed statistically significant changes in the concentration of fluoride in brain structures between study group and control animals. Moreover, significant changes in the expression level of COX1 and COX2, and in the concentration of PGE2 and TXB2 were observed. CONCLUSION: Exposure to fluoride in the prenatal and neonatal period result in the increase in COX2 activity and increase in PGE2 concentration in rats brain, which may lead to disturbances in central nervous system homeostasis.‬‬.

Kinetic [18F]-Fluoride of the Knee in Normal Volunteers.

PURPOSE: [F]-sodium fluoride ([F]NaF) is a well-established bone-seeking agent that has shown promise to assess bone turnover in a variety of disorders, but its distribution in healthy knee joints has not been explored. This study aimed to investigate parametric values for [F]NaF uptake in various bone tissues types of the knee and their spatial distributions. METHODS: Twelve healthy subjects were hand-injected with 92.5 MBq of [F]NaF and scanned on a 3-T PET/MRI system. Listmode PET data for both knees were acquired for 50 minutes from injection simultaneously with MRI Dixon and angiography data. The image-derived input function was determined from the popliteal artery. Using the Hawkins model, Patlak analysis was performed to obtain Ki (Ki) values and nonlinear regression analysis to obtain Ki, K1, k3/(k2 + k3), and blood volume. Comparisons for the measured kinetic parameters, SUV, and SUVmax were made between tissue types (subchondral, cortical, and trabecular bone) and between regional subsections of subchondral bone. RESULTS: Cortical bone had the highest [F]NaF uptake differing significantly in all measured parameters when compared with trabecular bone and significantly higher SUVmax and K1 than subchondral bone. Subchondral bone also had significantly higher SUV, SUVmax, and Ki than trabecular bone tissue. Regional differences were observed in K1 and k3/(k2 + k3) values. CONCLUSIONS: Quantitative [F]NaF PET is sensitive to variations in bone vascularization and metabolism in the knee joint.

Bioaccumulation of arsenic and fluoride in vegetables from growing media: health risk assessment among different age groups.

The current study was conducted to evaluate the arsenic (As) and fluoride (F-) concentrations in growing media (stored rainwater and soil), of district Tharparkar, Pakistan. The bioaccumulation/transportation of As and F from growing media to different types of vegetables (wild cucumis, Indian squish and cluster bean) was evaluated. Total concentrations of As and F- in stored rainwater samples were observed up to 585 µg/L and 32.4 mg/L, respectively, exceeding many folds higher than WHO provisional guideline values. The As and F- contents in soil samples of nine agricultural sites were found in the range of 121-254 mg/kg and 115-478 mg/kg, respectively. The highest contents of As and F- were observed in wild cucumis as compared to Indian squish and cluster bean (p < 0.05), grown in the same agricultural field. The bioaccumulation factors of As and F- were to be > 4.00, indicating the high rate of transportation of As and F- from growing media to vegetables. A significant positive correlation of As and F- in vegetables with their concentrations in soil and water was observed (r > 0.60 with p < 0.05). The risk assessment elucidated that the population of different age group consuming local vegetables and drinking water contaminated with As and F- may have adverse health effects.

Defluoridation of synthetic and industrial wastewater by using acidic activated alumina adsorbent: characterization and optimization by response surface methodology.

Excessive contamination of fluoride in wastewater is the cause of several chronic health problems. For this purpose, an adsorbent was prepared from alumina by acidic activation using sulfuric acid. The current research aims to find the maximum fluoride adsorption (%) from synthetic and industrial wastewater at optimum process parameters by using response surface methodology (RSM). All batch scale experiments were carried out according to the statistical-design order. Central composite design (CCD) was applied to ascertain the effect of adsorbent dose, pH, initial fluoride concentration and temperature on fluoride adsorption (%). Maximum fluoride removal was predicted based on the quadratic model developed. Validation of the model was done with negligible error. The regression coefficient of the model was found to be 0.96. From the analysis of variance (ANOVA), the factors with the greatest effect on the adsorption of fluoride were identified. Under optimized condition, the adsorbent dose 13.89 g L-1, pH 5.52, temperature 25 °C and initial fluoride concentration 18.67 mg L-1 resulted in 96% of maximum fluoride adsorption. Under the same optimized parameters, the fluoride adsorption from industrial wastewater found to be 92.10%.

Fluoride content in children's dentifrices marketed in Lima, Peru

Abstract The aim of the present study was to determine the concentration of total fluoride (TF) and total soluble fluoride (TSF) in children's dentifrices marketed in the city of Lima, Peru. Three samples of 23 dentifrices (4 without fluoride and 19 with fluoride) were purchased in different pharmacies in Lima, Peru. The TF and TSF concentrations found in the dentifrices were determined by ion-selective electrode, expressed in ppm F (μg F/g of dentifrice). The TF concentration in the majority of the fluoride toothpastes matched that shown on the label, except for one declared as 1450 ppm F by the manufacturer, whereas only 515.1 ppm F was found. The concentration of TSF found in the fluoride toothpastes ranged from 457.5 to 1134.8 ppm F. All the dentifrices were formulated with silica, but one also presented calcium carbonate. In conclusion, 83% of the children's dentifrices marketed in Lima, Peru, were fluoridated, but only 53% contained a TSF concentration greater than 1000 ppm F, the minimum concentration required to provide an anticaries effect.

A mini review of fluoride-induced apoptotic pathways.

Fluorine or fluoride can have toxic effects on bone tissue and soft tissue at high concentrations. These negative effects include but not limited to cytotoxicity, immunotoxicity, blood toxicity, and oxidative damage. Apoptosis plays an important role in fluoride-induced toxicity of kidney, liver, spleen, thymus, bursa of Fabricius, cecal tonsil, and cultured cells. Here, apoptosis activated by high level of fluoride has been systematically reviewed, focusing on three pathways: mitochondrion-mediated, endoplasmic reticulum (ER) stress-mediated, and death receptor-mediated pathways. However, very limited reports are focused on the death receptor-mediated apoptosis pathways in the fluoride-induced apoptosis. Therefore, understanding and discovery of more pathways and molecular mechanisms of fluoride-induced apoptosis may contribute to designing measures for preventing fluoride toxicity.

Tolerance strategies of two Mediterranean native xerophytes under fluoride pollution in Tunisia.

A field study was conducted along a fluorine gradient of soil pollution in Tunisia from Gabes, the most polluted site, to Smara, the reference site. Variations of fluoride (F) concentrations in soils were detected over 1 year in Gabes, Skhira, and Smara. F concentrations in the aerial part of two native plant species, i.e., Erodium glaucophyllum and Rhanterium suaveolens, were above the usual background concentrations. Bioaccumulation factors ranged from 0.08 to 1.3. With F concentrations in aerial parts up to 355 mg kg-1, both species may be described as F accumulators. Both species showed an earlier vegetative growth in Gabes than in Smara. However, some difference between their strategies could be observed, i.e., E. glaucophyllum shortening the period of its vegetative growth with an escape strategy and R. suaveolens decreasing its ratio of alive/dead parts potentially lowering the F toxicity by storage in dead cells. However, at a tissue level, mechanisms of tolerance were similar. Leaf section micrographs of both species showed a higher calcium accumulation in leaf midveins at Gabes than at Smara, confirming the role of calcium in plant F tolerance strategies.

Direct fluorine-18 labeling of heat-sensitive biomolecules for positron emission tomography imaging using the Al18F-RESCA method.

Positron emission tomography (PET) is a quickly expanding, non-invasive molecular imaging technology, and there is high demand for new specific imaging probes. Herein, we present a generic protocol for direct radiolabeling of heat-sensitive biomolecules with the positron-emitting radioisotope fluorine-18 (18F) using the aluminum fluoride restrained complexing agent (Al18F-RESCA) method. The Al18F-RESCA method combines the chemical advantages of a chelator-based radiolabeling method with the unique physical properties of the radionuclide of choice, fluorine-18. Proteins of interest can be conjugated to RESCA via amine coupling using (±)-H3RESCA-TFP, followed by purification using size-exclusion chromatography (SEC). Next, RESCA-derivatized biomolecules can be labeled in one step, at room temperature (~20 °C) in an aqueous medium with aluminum fluoride (Al18F). Al18F-labeled proteins can be obtained with moderate (12-17 GBq/µmol) to good (80-85 GBq/µmol) apparent molar activity, depending on the starting activity of 18F-. In addition, satisfactory radiochemical yields (35-55%, non-decay corrected) and high radiochemical purity (>98%, using gel filtration or solid-phase purification) are obtained. The mild radiolabeling procedure takes 0.5 h to complete and can be used for direct labeling of vector molecules such as peptides, protein scaffolds, and engineered antibody fragments.

F-18 fluoride uptake in primary breast cancer.

OBJECTIVE: Bone-specific radiotracers are known to accumulate in breast lesions. Tc-99m diphosphonates have been widely studied in differentiating breast lesions. In this retrospective study, we aimed to assess the uptake of the bone-specific PET radiotracer, F-18 fluoride (NaF), in primary breast cancers to determine its sensitivity and to identify any differences in NaF uptake between calcified and non-calcified tumors, histological subtypes, and patients with or without axillary lymphadenopathy. METHODS: NaF positron emission tomography/computed tomography (PET/CT) images of 69 newly diagnosed breast cancer patients were reviewed. F-18 fluoride uptake as maximum standardized uptake value (NaF SUVmax) was measured in the primary tumor, enlarged axillary lymph nodes and contralateral normal/non-tumoral breast tissue. Low-dose CT images were reviewed to locate the primary tumor and grossly assess its calcification and check for ipsilateral axillary lymphadenopathy. Whole body NaF PET/CT images were reviewed to search for bone metastases. Eighteen patients also underwent F-18 fluorodeoxyglucose (FDG) PET/CT study. RESULTS: The primary breast tumor was clearly seen as focal or diffuse uptake on NaF PET images in 27 of 69 patients (39%) (mean NaF SUVmax: 2.0 ± 1.0). In the rest, there was only mild bilateral diffuse breast uptake. When analyzing images per histological subtype (42 patients, 43 tumors), 14 of 31 invasive ductal carcinomas (IDC) (45%) and 3 of 4 ductal carcinoma in situ (DCIS) were visible on PET. Five invasive lobular carcinomas, 2 invasive mammary carcinomas, and 1 mucinous carcinoma were not visible on PET. Mean NaF SUVmax of contralateral normal/non-tumoral breast tissue was 1.0 ± 0.4. There was no significant difference in mean NaF SUVmax of primary tumor in cases with and without calcification or with and without axillary lymphadenopathy (p 0.892 and 0.957). There was no correlation between NaF SUVmax and FDG SUVmax values of the primary tumors (r 0.072, p 0.797, Pearson correlation). CONCLUSION: NaF PET has relatively low sensitivity in detecting breast cancer. However, abnormal breast uptake on NaF PET requires further evaluation. F-18 fluoride uptake in the primary breast tumor does not seem to be correlated with axillary lymphadenopathy (metastasis potential), gross tumor calcification or metabolic activity of the tumor.