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1.
Metallomics ; 14(10)2022 10 18.
Article in English | MEDLINE | ID: mdl-36201445

ABSTRACT

Non-invasive imaging techniques to dynamically map whole-body trafficking of essential metals in vivo in health and diseases are needed. Despite 62Zn having appropriate physical properties for positron emission tomography (PET) imaging (half-life, 9.3 h; positron emission, 8.2%), its complex decay via 62Cu (half-life, 10 min; positron emission, 97%) has limited its use. We aimed to develop a method to extract 62Zn from a 62Zn/62Cu generator, and to investigate its use for in vivo imaging of zinc trafficking despite its complex decay. 62Zn prepared by proton irradiation of natural copper foil was used to construct a conventional 62Zn/62Cu generator. 62Zn was eluted using trisodium citrate and used for biological experiments, compared with 64Cu in similar buffer. PET/CT imaging and ex vivo tissue radioactivity measurements were performed following intravenous injection in healthy mice. [62Zn]Zn-citrate was readily eluted from the generator with citrate buffer. PET imaging with the eluate demonstrated biodistribution similar to previous observations with the shorter-lived 63Zn (half-life 38.5 min), with significant differences compared to [64Cu]Cu-citrate, notably in pancreas (>10-fold higher at 1 h post-injection). Between 4 and 24 h, 62Zn retention in liver, pancreas, and kidney declined over time, while brain uptake increased. Like 64Cu, 62Zn showed hepatobiliary excretion from liver to intestines, unaffected by fasting. Although it offers limited reliability of scanning before 1 h post-injection, 62Zn-PET allows investigation of zinc trafficking in vivo for >24 h and hence provides a useful new tool to investigate diseases where zinc homeostasis is disrupted in preclinical models and humans.


Subject(s)
Thiosemicarbazones , Zinc Radioisotopes , Animals , Citrates , Copper , Copper Radioisotopes , Humans , Mice , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography/methods , Protons , Reproducibility of Results , Tissue Distribution , Tomography, X-Ray Computed , Zinc
2.
Curr Radiopharm ; 14(4): 325-339, 2021.
Article in English | MEDLINE | ID: mdl-32867656

ABSTRACT

The present review describes the methodological aspects and prospects of the production of Positron Emission Tomography (PET) radiometals in a liquid target using low-medium energy medical cyclotrons. The main objective of this review is to delineate and discuss the critical factors involved in the liquid target production of radiometals, including type of salt solution, solution composition, beam energy, beam current, the effect of irradiation duration (length of irradiation) and challenges posed by in-target chemistry in relation with irradiation parameters. We also summarize the optimal parameters for the production of various radiometals in liquid targets. Additionally, we discuss the future prospects of PET radiometals production in the liquid targets for academic research and clinical applications. Significant emphasis has been given to the production of 68Ga using liquid targets due to the growing demand for 68Ga labeled PSMA vectors, [68Ga]- Ga-DOTATATE, [68Ga]Ga-DOTANOC and some upcoming 68Ga labeled radiopharmaceuticals. Other PET radiometals included in the discussion are 86Y, 63Zn and 89Zr.


Subject(s)
Cyclotrons , Gallium Radioisotopes/chemistry , Positron-Emission Tomography , Radiochemistry/methods , Radioisotopes/chemistry , Radiopharmaceuticals/chemical synthesis , Yttrium Radioisotopes/chemistry , Zinc Radioisotopes/chemistry , Zirconium/chemistry
3.
Chemosphere ; 254: 126863, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32957281

ABSTRACT

In urban set up, increasing combustion and processing activities have contaminated the air with toxic heavy metals which are generally enriched on atmospheric particulate matter. Vegetation around urban area act as a sink where such metal enriched particles generally deposit on the foliar surfaces, however, role of vegetation in uptake of metals adhered on the atmospheric particulate matter is yet not explored properly and is important to study to evaluate their role as bio-remediator. The undertaken work examines the foliar surface of Morus alba for its potential to deposit and accumulate atmospheric heavy metals. Further, to understand foliar uptake mechanism and translocation of atmospheric metal enriched on particulate matter a simulated experiment was conducted by labeling the known particle size (45 µm and 120 µm) with radio labeled 65Zn, applied on the tagged leaf with two particle loads, 25 mg and 50 mg. The study showed that owing to its rough foliar surface with trichomes and grooves, Morus alba efficiently trap heavy metal enriched particles and was capable of accumulating metals from particulate matter into different plant parts. It was recorded that 65Zn adhered on different size particles was taken up by tagged leaf of mulberry and majorly translocated to the lower stem and roots. It was also inferred from the study that both particle size and particle load significantly affect the foliar uptake and translocation of atmospheric heavy metal. The study focuses on the fact that urban avenue trees are capable of taking up atmospheric heavy metals and can play a crucial role in improving air quality.


Subject(s)
Air Pollutants/metabolism , Morus/metabolism , Particulate Matter/pharmacokinetics , Zinc/pharmacokinetics , Air Pollutants/pharmacokinetics , Air Pollution , Biodegradation, Environmental , Particle Size , Particulate Matter/analysis , Particulate Matter/chemistry , Plant Leaves/metabolism , Plant Roots/metabolism , Radioactive Tracers , Zinc Radioisotopes/pharmacokinetics
4.
J Radiol Prot ; 40(3): 848-860, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32575092

ABSTRACT

Collimating apertures are used in proton therapy to laterally conform treatment fields to the target volume. While this is a standard technique in passive spreading treatment heads, patient-specific apertures can supplement pencil-beam scanning (PBS) techniques to sharpen the lateral dose fall-off. A radiation protection issue is that proton-induced nuclear reactions can lead to the formation of radionuclides in the apertures. In the experiments of the current study, cylindrical, thick brass targets were irradiated with quasi-monoenergetic proton fields of 100.0 MeV and of 226.7 MeV in PBS mode. The radioactivation of these two brass samples was characterised with a low-level gamma-ray spectrometer. The activation products were scored in a Monte Carlo simulation, too, and compared with the experimental activities. For the high-energy field, 63Zn, 60Cu, and 61Cu were the most important short-lived isotopes regarding the measured specific activity. After irradiation with the 100.0 MeV field, 62Cu, 63Zn, and 60Cu had the highest activity. Regarding long-lived isotopes, which determine the storage time of the used apertures, the isotopes 57Co, 65Zn, 54Mn, 56Co had the largest contribution to the activity. The relative difference of activities between simulation and experiment was typically between 10%-20% for short-lived nuclides and were up to a factor of five larger for long-lived nuclides. Summarising experiments and simulations for both incident proton energies, 62Cu was the most important detected residual nucleus regardless if specific activity or equivalent dose is considered.


Subject(s)
Copper/chemistry , Proton Therapy/methods , Radiation Protection/methods , Zinc/chemistry , Copper Radioisotopes , Humans , Monte Carlo Method , Radiometry/instrumentation , Radiotherapy Dosage , Spectrometry, Gamma , Zinc Radioisotopes
5.
Dalton Trans ; 49(19): 6249-6258, 2020 May 19.
Article in English | MEDLINE | ID: mdl-32329503

ABSTRACT

Copper-based radiopharmaceuticals are of high interest these days owing to the decay properties of copper radioisotopes. In contrast, labeled zinc compounds have been less studied for applications in nuclear medicine. In this study, the stability of labeled zinc and copper complexes with two azacrown ether ligands was investigated and compared. Then, the in vitro and in vivo stability of the studied zinc complexes was demonstrated, with the complexes showing promise for biomedical applications. In contrast, analogous copper complexes quickly dissociated in the presence of serum proteins. Furthermore, a simple method for the production of radiochemically pure 65Zn was proposed, and the opportunity for its use as a surrogate radionuclide for research into potential zinc-containing radiopharmaceuticals was demonstrated.


Subject(s)
Coordination Complexes/chemistry , Copper/chemistry , Crown Ethers/chemistry , Zinc/chemistry , Animals , Coordination Complexes/blood , Coordination Complexes/urine , Crystallography, X-Ray , Ligands , Magnetic Resonance Spectroscopy , Male , Mice , Mice, Inbred BALB C , Molecular Conformation , Zinc Radioisotopes/chemistry
6.
J Environ Radioact ; 217: 106220, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32217252

ABSTRACT

Abnormal particulate radionuclides (65Zn, 134Cs and 137Cs) were detected at the CTBTO RN58 station which is located near North Korea between 12 and March 14, 2016. Detection ratio for caesium (134Cs/137Cs) shows that the product origin was nuclear explosion and dilution factors at RN58, released from DPRK test site, show clear correlation with radioactivity concentration of two samples. The detected radionuclides may be originated from the third nuclear test, February 2013. Half-life, radionuclides fractionation, MDC, and device design are attributed to no detection of other nuclides. Most of radionuclides have been decayed away and relatively long half-life nuclides might be in the third test site but they were displaced deep inside the area by fractionation during the explosion. Considering 65Zn activity ratio to 137Cs which is higher than historical ratios at Brunswick in 1968, there is a possibility that the third DPRK nuclear test was a "salted" nuclear bomb test using zinc as jacket instead of fissionable 238U around the secondary stage fusion fuel.


Subject(s)
Fukushima Nuclear Accident , Radiation Monitoring , Radioactivity , Air Pollutants, Radioactive , Cesium Radioisotopes , Democratic People's Republic of Korea , Zinc , Zinc Radioisotopes
7.
Sci Total Environ ; 653: 131-139, 2019 Feb 25.
Article in English | MEDLINE | ID: mdl-30408661

ABSTRACT

To understand the potential risks of dietary metals to marine bivalves, it is important to study the interaction between dietary metal bioaccumulation and bivalve feeding behavior. Key processes in affecting the dietary metal influx are the selection of different particles during the ingestion process as well as the differential assimilation of metals during the digestion process. In this study, we quantified the influences of seston quality and quantity on the dietary assimilation of Cd and Zn as well as pre-ingestion particle selectivity in a razor clam Sinonovacula constricta following feeding on radiolabeled diatoms and sediments with different mixtures at four food concentrations. Bioavailability of 109Cd and 65Zn from seston was measured by assimilation efficiency (AE) using a pulse-chase feeding technique. The AEs of Cd and Zn were significantly affected by the seston quantity and quality (higher for Zn than they were for Cd and higher for diatoms than for suspended sediments), but were independent of the presence of other particles during the feeding process. Dual gamma radiotracer technique was further employed to study pre-ingestion particle selectivity. Particle selectivity was weak during pre-ingestion in razor clams, although there was evidence that clams might be able to differentiate particles during the process of pseudofeces production. Our study demonstrated that seston composition and quantity substantially affected the bioavailability of Cd and Zn to the razor clams. The results are important to understand the bioaccumulation of metals in clams living in dynamic food environments of estuary.


Subject(s)
Bivalvia/metabolism , Cadmium Radioisotopes/metabolism , Environmental Monitoring , Water Pollutants, Chemical/metabolism , Zinc Radioisotopes/metabolism , Animals , Biological Availability , Diet , Estuaries , Tissue Distribution
8.
Environ Sci Pollut Res Int ; 25(22): 22120-22135, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29802617

ABSTRACT

A comparative study between two nanosorbents, nanopolyaniline (NPANI) and nanopolyaniline coated with nanosilver oxide (NPANI-NAg2O) is explored to dispose the divalent species of Zn/Co from water and radioactive isotopes 65Zn/60Co from radioactive wastewater using batch and column techniques. NPANI-NAg2O nanocomposite was synthesized via solid-solid reaction. Characterization was achieved using FT-IR, TGA, XRD, SEM, HR-TEM, and surface area analysis. The images of SEM and HR-TEM confirmed the success of the modification process and the particle size was found in the range 28.78-68.28 nm (NPANI) and 25.74-85.71 nm (NPANI-NAg2O), respectively. Solution pH, contact time, solid dosage, and ionic concentration of the metals were studied as fundamental factors. The obtained results indicated that the optimum conditions to dispose Zn/Co divalent species using NPANI were pH 7 and 30-33 min, while NPANI-NAg2O exhibited the optimum conditions at pH 7 and 20-30 min. The maximum removal capacities were 100.1 and 139.75 mg/g for Zn(II) and 57.93 and 112.1 mg/g for Co(II) using NPANI and NPANI-NAg2O, respectively. Graphical abstract ᅟ.


Subject(s)
Aniline Compounds/chemical synthesis , Cobalt Radioisotopes/chemistry , Nanocomposites/chemistry , Oxides/chemistry , Silver Compounds/chemistry , Water Pollutants, Radioactive/isolation & purification , Zinc Radioisotopes/chemistry , Adsorption , Green Chemistry Technology , Particle Size , Spectroscopy, Fourier Transform Infrared , Wastewater/chemistry , Water Purification/methods , Zinc
9.
Ecotoxicol Environ Saf ; 145: 665-673, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28843201

ABSTRACT

A novel material was designed using layer-by-layer functionalization of nanobentonite with nanopolyaniline and oleic acid to produce an efficient NBent-NPA-OA nanosorbent to adsorb the divalent ionic Zn/Co and their radioisotopes 65Zn/60Co from tap water and radioactive wastewater. The new nanosorbent was characterized by Fourier-transform-infrared (FT-IR), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM) and determination of surface area. The NBent-NPA-OA particle size was ranged between 9.45 and 33.60nm according to HR-TEM analysis. The FT-IR exhibited several characteristic absorption peaks due to the existence of deposited layers of nanopolyaniline and oleic acid on the surface of nanobentonite surface. Different experimental parameters including, initial pH, contact time, nanosorbent, initial concentration of the target metals and interfering ions were varied, investigated and optimized to evaluate the removal efficiency of the divalent ionic Zn/Co from their solutions by the action of NBent-NPA-OA nanosorbent. The collected batch equilibrium results confirmed the efficiency of newly functionalized NBent-NPA-OA nanosorbent to uptake the divalent ionic Zn/Co from their solutions (10.0mL of 0.01mol/L) with maximum capacity values 2.916 and 1.960mmolg-1, respectively using 5.0mg nanosorbent, pH 6.0 and 20min contact reaction time. The multistage microcolumn system was successfully implemented to remove the divalent ionic Zn/Co from tap water in addition to their radioisotopes 65Zn/60Co from radioactive wastewater. The current study refers to an excellent recovery and the removal percent of the radioisotopes 65Zn (96.4) and 60Co (92.7%) using NBent-NPA-OA nanosorbent.


Subject(s)
Aniline Compounds/chemistry , Bentonite/chemistry , Nanoparticles/chemistry , Oleic Acid/chemistry , Wastewater/chemistry , Water Pollutants, Radioactive/analysis , Water Purification/methods , Adsorption , Cations, Divalent/analysis , Cobalt/analysis , Cobalt Radioisotopes , Water Pollutants, Chemical/analysis , Zinc/analysis , Zinc Radioisotopes
10.
Chemosphere ; 183: 503-509, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28570893

ABSTRACT

Trophic transfer of Zn in fish is affected by the type of food and environmental variables such as temperature. However, there is still a lack of knowledge regarding the effects of such factors on Zn organotropism. For this reason, a series of experimental studies have investigated how the distribution and the concentration of Zn is affected by some environmentally-relevant factors (food quality, food availability, water pH, and temperature) in turbot Scophthalmus maximus using radiotracer techniques. In three different experiments, Zn distribution in seven body compartments of juvenile turbot and the calculation of Zn concentration index (IC) for each compartment were compared. Its distribution as well as its concentration in the body compartments of juvenile turbots were not affected by the experimental conditions tested. This apparent consistency in the Zn organotropism can be explained by the ability of the fish to maintain Zn homeostasis at non-toxic Zn concentrations in their diet. These results are important to better understand the trophic transfer of Zn in fish under realistic environmental conditions.


Subject(s)
Diet , Flatfishes/metabolism , Water Pollutants, Chemical/metabolism , Zinc/metabolism , Animal Feed , Animals , Feeding Behavior , Food Chain , Food Quality , Hydrogen-Ion Concentration , Organ Specificity , Seafood , Temperature , Tissue Distribution , Water Pollutants, Chemical/pharmacokinetics , Water Pollutants, Chemical/toxicity , Zinc/pharmacokinetics , Zinc/toxicity , Zinc Radioisotopes
11.
Environ Toxicol Chem ; 36(5): 1227-1234, 2017 05.
Article in English | MEDLINE | ID: mdl-27704601

ABSTRACT

Diet is an important pathway for metal uptake in marine organisms, and assimilation efficiency is one of the most relevant parameters to quantify trophic transfer of metals along aquatic food webs. The most commonly used method to estimate this parameter is pulse-chase feeding using radiolabeled food. This approach is, however, based on several assumptions that are not always tested in an experimental context. The present study aimed to validate the approach by assessing single-feeding and multiple-feeding approaches, using a model species (the turbot Scophthalmus maximus). Using the kinetic data obtained from the single-feeding experiment, the reconstruction of a multi-feeding experiment was tested for consistency with data provided by an actual multi-feeding performed under the same experimental conditions. The results validated the single-feeding approach. Environ Toxicol Chem 2017;36:1227-1234. © 2016 SETAC.


Subject(s)
Diet , Flatfishes/metabolism , Metals/metabolism , Animals , Cadmium Radioisotopes/chemistry , Cadmium Radioisotopes/metabolism , Cobalt Radioisotopes/chemistry , Cobalt Radioisotopes/metabolism , Isotope Labeling , Kinetics , Metals/chemistry , Zinc Radioisotopes/chemistry , Zinc Radioisotopes/metabolism
12.
Mol Imaging ; 152016.
Article in English | MEDLINE | ID: mdl-27941122

ABSTRACT

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B (11C-PiB) and 18F-fluorodeoxyglucose (18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-ß plaque burden (11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-ß pathology, warranting further imaging studies of zinc homeostasis in patients with AD.


Subject(s)
Alzheimer Disease/diagnostic imaging , Citrates/administration & dosage , Positron-Emission Tomography/methods , Radiopharmaceuticals/administration & dosage , Zinc Radioisotopes/chemistry , Aged , Aged, 80 and over , Alzheimer Disease/metabolism , Brain/diagnostic imaging , Brain/metabolism , Citrates/chemistry , Citrates/pharmacokinetics , Female , Fluorodeoxyglucose F18 , Healthy Volunteers , Humans , Male , Middle Aged , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution , Urine/chemistry
13.
Appl Radiat Isot ; 105: 20-25, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26226219

ABSTRACT

The proton beam energy of an isochronous 18MeV cyclotron was determined using a novel version of the stacked copper-foils technique. This simple method used stacked foils of natural copper forming 'thick' targets to produce Zn radioisotopes by the well-documented (p,x) monitor-reactions. Primary beam energy was calculated using the (65)Zn activity vs. depth profile in the target, with the results obtained using (62)Zn and (63)Zn (as comparators) in close agreement. Results from separate measurements using foil thicknesses of 100, 75, 50 or 25µm to form the stacks also concurred closely. Energy was determined by iterative least-squares comparison of the normalized measured activity profile in a target-stack with the equivalent calculated normalized profile, using 'energy' as the regression variable. The technique exploits the uniqueness of the shape of the activity vs. depth profile of the monitor isotope in the target stack for a specified incident energy. The energy using (65)Zn activity profiles and 50-µm foils alone was 18.03±0.02 [SD] MeV (95%CI=17.98-18.08), and 18.06±0.12MeV (95%CI=18.02-18.10; NS) when combining results from all isotopes and foil thicknesses. When the beam energy was re-measured using (65)Zn and 50-µm foils only, following a major upgrade of the ion sources and nonmagnetic beam controls the results were 18.11±0.05MeV (95%CI=18.00-18.23; NS compared with 'before'). Since measurement of only one Zn monitor isotope is required to determine the normalized activity profile this indirect yet precise technique does not require a direct beam-current measurement or a gamma-spectroscopy efficiency calibrated with standard sources, though a characteristic photopeak must be identified. It has some advantages over published methods using the ratio of cross sections of monitor reactions, including the ability to determine energies across a broader range and without need for customized beam degraders.


Subject(s)
Cyclotrons/statistics & numerical data , Protons , Zinc Radioisotopes , Copper , Humans , Radiometry/statistics & numerical data , Zinc Radioisotopes/analysis
14.
Cancer Biother Radiopharm ; 29(8): 310-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25226565

ABSTRACT

This study was conducted to investigate the role of curcumin and zinc on the biokinetics and biodistribution of (65)Zn during colon carcinogenesis. Male wistar rats were divided into five groups, namely normal control, 1,2-dimethylhydrazine (DMH) treated, DMH + curcumin treated, DMH + zinc treated, and DMH + curcumin + zinc treated. Weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks initiated colon carcinogenesis. Curcumin (100 mg/kg body weight orally) and ZnSO4 (227 mg/L in drinking water) were supplemented for 16 weeks. This study revealed a significant depression in the fast (Tb1) and slow component (Tb2) of biological half-life of (65)Zn in the whole body of DMH-treated rats, whereas liver showed a significant elevation in these components. Further, DMH treatment showed a significant increase in the uptake values of (65)Zn in colon, small intestine, and kidneys. Subcellular distribution depicted a significant increase in (65)Zn uptake values in mitochondrial, microsomal, and postmicrosomal fractions of colon. However, curcumin and zinc supplementation when given separately or in combination reversed the trends and restored the uptake values close to normal range. Our study concludes that curcumin and zinc supplementation during colon carcinogenesis shall prove to be efficacious in regulating the altered zinc metabolism.


Subject(s)
Colonic Neoplasms/metabolism , Curcumin/pharmacology , Zinc Radioisotopes/pharmacokinetics , Zinc/pharmacology , 1,2-Dimethylhydrazine , Animals , Carcinogenesis , Carcinogens , Male , Rats , Rats, Wistar
15.
J Nucl Med ; 55(8): 1348-54, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25047329

ABSTRACT

UNLABELLED: Abnormalities of zinc homeostasis are indicated in many human diseases. A noninvasive imaging method for monitoring zinc in the body would be useful to understand zinc dynamics in health and disease. To provide a PET imaging agent for zinc, we have investigated production of (63)Zn (half-life, 38.5 min) via the (63)Cu(p,n)(63)Zn reaction using isotopically enriched solutions of (63)Cu-copper nitrate. A solution target was used for rapid isolation of the (63)Zn radioisotope from the parent (63)Cu ions. Initial biologic evaluation was performed by biodistribution and PET imaging in normal mice. METHODS: To produce (63)Zn, solutions of (63)Cu-copper nitrate in dilute nitric acid were irradiated by 14-MeV protons in a low-energy cyclotron. An automated module was used to purify (63)Zn from (63)Cu in the target solution. The (63)Cu-(63)Zn mixture was trapped on a cation-exchange resin and rinsed with water, and the (63)Zn was eluted using 0.05 N HCl in 90% acetone. The resulting solution was neutralized with NaHCO3, and the (63)Zn was then trapped on a carboxymethyl cartridge, washed with water, and eluted with isotonic 4% sodium citrate. Standard quality control tests were performed on the product according to current good manufacturing practice, including radionuclidic identity and purity, and measurement of nonradioactive Zn(+2), Cu(+2), Fe(+3), and Ni(+2) by ion-chromatography high-performance liquid chromatography. Biodistribution and PET imaging studies were performed in B6.SJL mice after intravenous administration of (63)Zn-zinc citrate. (63)Cu target material was recycled by eluting the initial resin with 4N HNO3. RESULTS: Yields of 1.07 ± 0.22 GBq (uncorrected at 30-36 min after end of bombardment) of (63)Zn-zinc citrate were obtained with a 1.23 M (63)Cu-copper nitrate solution. Radionuclidic purity was greater than 99.9%, with copper content lower than 3 µg/batch. Specific activities were 41.2 ± 18.1 MBq/µg (uncorrected) for the (63)Zn product. PET and biodistribution studies in mice at 60 min showed expected high uptake in the pancreas (standard uptake value, 8.8 ± 3.2), liver (6.0 ± 1.9), upper intestine (4.7 ± 2.1), and kidney (4.2 ± 1.3). CONCLUSION: A practical and current good manufacturing practice-compliant preparation of radionuclidically pure (63)Zn-zinc citrate has been developed that will enable PET imaging studies in animal and human studies. (63)Zn-zinc citrate showed the expected biodistribution in mice.


Subject(s)
Citrates , Positron-Emission Tomography/methods , Zinc/metabolism , Animals , Biomarkers/metabolism , Citrates/pharmacokinetics , Humans , Male , Mice , Tissue Distribution , Zinc Radioisotopes
16.
Ann Nucl Med ; 28(9): 880-90, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25023233

ABSTRACT

OBJECTIVE: The development of a new tracer based on the cyclic sulfonamides (sultams) was investigated. METHODS: 3-(Methoxy-phenyl-methyl)-1,6-dimethyl-1H benzo[c][1,2] thiazine 2,2-dioxide (benzo-δ-sultam) was synthesized and characterized by elemental analysis, FT-IR spectroscopy and single crystal X-ray structure determination. The prepared cyclic sulfonamide was labeled with non-commercial (62)Zn radioisotope for fast in vivo targeting and Coincidence imaging purposes (radiochemical purity 97 % ITLC, 96 % HPLC, specific activity 20-23 GBq/mmol). In vivo biodistribution of the final complex was investigated in Sprague Dawley(®) rats bearing fibro sarcoma tumor after 2, 4 and 8 h post injection and compared with free Zn(+2) cation. RESULTS: Using instant paper chromatography method, the physicochemical properties of labeled compounds were found sufficiently stable in organic phases, e.g. a human serum, to be reliably used in bioapplications. CONCLUSIONS: The complex exhibited a rapid as well as high tumor uptake (tumor to blood ratio 4.38 and tumor to muscle ratio 9.63) resulting in an efficient tumor targeting agent.


Subject(s)
Naphthalenesulfonates , Positron-Emission Tomography/methods , Radiopharmaceuticals , Zinc Radioisotopes , Animals , Chromatography, High Pressure Liquid , Chromatography, Paper , Humans , Molecular Structure , Naphthalenesulfonates/chemical synthesis , Naphthalenesulfonates/chemistry , Naphthalenesulfonates/pharmacokinetics , Neoplasms, Experimental/diagnostic imaging , Positron-Emission Tomography/instrumentation , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacokinetics , Rats, Sprague-Dawley , Sarcoma/diagnostic imaging , Serum/chemistry , Spectroscopy, Fourier Transform Infrared , Zinc Radioisotopes/chemistry , Zinc Radioisotopes/pharmacokinetics
17.
Appl Radiat Isot ; 91: 38-43, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24886964

ABSTRACT

The performance of a commercially produced (62)Zn/(62)Cu microgenerator system, and an associated kit-based radiopharmaceutical synthesis method, was evaluated for clinical site production of [(62)Cu]Cu-ETS (ethylglyoxal bis(thiosemicarbazonato)copper(II)), an investigational agent for PET perfusion imaging. Using 37 generators, containing 1.84±0.23 GBq (62)Zn at 9:00 AM on the day of clinical use, a total of 45 patient doses of [(62)Cu]Cu-ETS (672±172 MBq) were delivered without difficulty. (62)Cu elution yields were high (approximately 90%), accompanied by extremely low (62)Zn breakthrough (<0.001%). Radiopharmaceutical preparation, from the start-of-elution to time-of-injection, consumed less than five minutes. The (62)Zn/(62)Cu microgenerator was a dependable source of short-lived positron-emitting (62)Cu, and the kit-based synthesis proved to be rapid, robust, and highly reliable for "on-demand" delivery of [(62)Cu]Cu-ETS for PET perfusion imaging.


Subject(s)
Copper Radioisotopes/chemistry , Organometallic Compounds/chemical synthesis , Perfusion Imaging/methods , Radionuclide Generators/instrumentation , Radiopharmaceuticals/chemical synthesis , Thiosemicarbazones/chemical synthesis , Zinc Radioisotopes/chemistry , Head and Neck Neoplasms/diagnostic imaging , Humans , Kidney Neoplasms/diagnostic imaging , Positron-Emission Tomography/methods
18.
Bioorg Med Chem ; 22(8): 2563-70, 2014 Apr 15.
Article in English | MEDLINE | ID: mdl-24656799

ABSTRACT

Positron-emission tomography (PET) can be used to visualize active stage cancer. Fluorine-18 ([(18)F])-labeled 2-([(18)F])2-deoxy-2-fluoroglucose (([(18)F])-FDG), which accumulates in glucose-dependent tissues, is a good cancer-targeting tracer. However, ([(18)F])-FDG is obscured in glucose-dependent normal tissues. In this study, we assessed the cancer-selective accumulation of zinc-labeled glycoconjugated 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (ZnGlc1-4), both in vitro and in vivo. Experiments using both normal and cancer cells confirmed the relationship between cancer cell-selective accumulation and the substitution numbers and orientations of glycoconjugated porphyrins. ZnGlctrans-2 accumulated at greater levels in cancer cells compared with other glycoconjugated porphyrins. PET imaging showed that ZnGlctrans-2 accumulated in tumor.


Subject(s)
Porphyrins/chemistry , Radiopharmaceuticals/chemistry , Animals , Cell Line, Tumor , Magnetic Resonance Imaging , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasms/diagnostic imaging , Porphyrins/metabolism , Positron-Emission Tomography , Radiopharmaceuticals/metabolism , Rats , Tissue Distribution , Transplantation, Heterologous , Zinc Radioisotopes/chemistry
19.
Environ Sci Pollut Res Int ; 21(12): 7624-30, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24604268

ABSTRACT

The focus of this article was to explore the translocation of (109)Cd, (57)Co, (65)Zn, (63)Ni, and (134)Cs via xylem and phloem in the newly found hyperaccumulator Solanum nigrum L. Two experiments with the uptake via the roots and transport of (109)Cd, (57)Co, and (65)Zn labeled by roots, and the redistribution of (109)Cd, (65)Zn, (57)Co, (63)Ni, and (134)Cs using flap label in S. nigrum in a hydroponic culture with a standard nutrient solution were conducted. The results showed that (109)Cd added for 24 h to the nutrient medium of young plants was rapidly taken up, transferred to the shoot, and accumulated in the cotyledons and the oldest leaves but was not efficiently redistributed within the shoot afterward leading to a rather low content in the fruits. In contrast, (57)Co was more slowly taken up and released to the shoot, but afterward, this element was redistributed from older leaves to younger leaves and maturing fruits. (65)Zn was rapidly taken up and transferred to the shoot (mainly to the youngest leaves and not to the cotyledons). Afterward, this radionuclide was redistributed within the shoot to the youngest organs and finally accumulated in the maturing fruits. After flap labeling, all five heavy metals tested ((109)Cd, (57)Co, (65)Zn, (63)Ni, (134)Cs) were exported from the labeled leaf and redistributed within the plant. The accumulation in the fruits was most pronounced for (63)Ni and (65)Zn, while a relatively high percentage of (57)Co was finally found in the roots. (134)Cs was roughly in the middle of them. The transport of (109)Cd differed from that previously reported for wheat or lupin and might be important for the potential of S. nigrum to hyperaccumulate cadmium.


Subject(s)
Metals, Heavy/pharmacokinetics , Solanum nigrum/metabolism , Cadmium Radioisotopes/metabolism , Cesium Radioisotopes/pharmacokinetics , Cobalt Radioisotopes/pharmacokinetics , Hydroponics , Nickel/pharmacokinetics , Phloem/metabolism , Plant Leaves/metabolism , Plant Roots/metabolism , Radioisotopes/pharmacokinetics , Xylem/metabolism , Zinc Radioisotopes/pharmacokinetics
20.
Phys Med Biol ; 59(4): 837-51, 2014 Feb 21.
Article in English | MEDLINE | ID: mdl-24487508

ABSTRACT

In plant research, radioisotope imaging provides useful information about physiological activities in various tissues and elemental transport between plant organs. To expand the usage of imaging techniques, a new system was developed to visualize beta particles, x-rays and gamma-rays emitted from plant bodies. This real-time radioisotope imaging system (RRIS) visualizes radioactivity after conversion into light with a CsI(Tl) scintillator plate. Herein, the RRIS detection properties of the gamma-ray emitters (22)Na, (65)Zn, (86)Rb, (109)Cd and (137)Cs were evaluated in comparison with those of radioluminography (RLG) using an imaging plate. The lower quantitative detection limit (Bq mm(-2)) during a 15 min period ranged from 0.1 to 4, depending on the nuclide, similar to that of RLG. When the quantitative ability to detect radiation from various Arabidopsis tissues was analyzed, the quantitative capability in silique and the thick internode tended to be low. In an EGS5 simulation, beta particles were the greatest contributors to RRIS imaging of (22)Na, (86)Rb and (137)Cs, and low-energy x-rays contributed significantly to (65)Zn and (109)Cd detection. Thus, both self-absorption and air space between the sample and scintillator surface could impair quantitative RRIS imaging. Despite these issues, RRIS is suggested for quantitative time-course measurements of radionuclide motion within plants.


Subject(s)
Arabidopsis/metabolism , Radioisotopes/metabolism , Radionuclide Imaging/methods , Cadmium Radioisotopes/chemistry , Cadmium Radioisotopes/metabolism , Cesium Radioisotopes/chemistry , Cesium Radioisotopes/metabolism , Radiochemistry , Radioisotopes/chemistry , Rubidium Radioisotopes/chemistry , Rubidium Radioisotopes/metabolism , Sodium Radioisotopes/chemistry , Sodium Radioisotopes/metabolism , Time Factors , Zinc Radioisotopes/chemistry , Zinc Radioisotopes/metabolism
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