Experimental and theoretical study of rhenium radioisotopes production for manufacturing of new compositional radiopharmaceuticals.

Rhenium therapeutic radioisotopes, namely rhenium-186 and 188, are radionuclides that have been used in combination with various ligands to provide different radiopharmaceuticals for the treatment of different diseases for many years. Each of these radioisotopes has its own special attributes, which make it appropriate to destroy special-sized tumors. High energy, long range beta particles in 188Re can give this certainty that large tumors can be eradicated with high efficiency. On the other hand, 186Re with low energy, short range beta particles is adequate item to ruin small tumors with minimum side effects and high yield. Thus, each of these radioisotopes has features that can cover just part of the treatment individually. So we thought accompanying 186Re and 188Re must have the best outcome to treat tumors with various sizes. Irradiating natural rhenium with neutrons has this potential to produce parallel 186Re and 188R together. We are looking for investigating whether the natural rhenium irradiation, in addition the concurrent production of these radioisotopes, gives us the appropriate radioactivity values to produce compositional radiopharmaceuticals? In this research, the experimental and theoretical assessments of 186Re and 188R simultaneous production to reach compositional radiopharmaceutical by natural rhenium irradiation in the Tehran research reactor, as well as the type and amount of produced impurities have been investigated. The results showed that experimental data are in good agreement with theoretical calculations. The maximum relative error in data has been calculated 8%. The results showed that, in the simultaneous production 186Re and 188R via the natural rhenium irradiation method, the amounts of impurities are trivial compared to the main products, and the activities of main products are properly enough to produce compositional radiopharmaceuticals.

Improved freeze-dried kit for the preparation of 188ReN-DEDC/lipiodol for the therapy of unresectable hepatocellular carcinoma.

Rhenium-188-N-(DEDC)2/lipiodol (abbreviated as 188ReN-DEDC, where DEDC = monoanionic diethyldithiocarbamate) is a clinically proven radiopharmaceutical for the therapy of unresectable hepatocellular carcinoma (HCC) through trans arterial radioembolization (TARE). A two-vial freeze-dried kit for the preparation of [188ReN(DEDC)2] complex using sodium perrhenate (Na188ReO4) obtained from a commercial Tungsten-188/Rhenium-188 generator had been reported earlier. This method required addition of stipulated volume of glacial acetic acid into vial 1 by the user for efficient preparation of [188ReN]2+ intermediate. An error in this step can result in low radiochemical yield of [188ReN]2+ intermediate as well as sub-optimal pH of the reaction mixture for the second step, leading to poor radiochemical purity of 188ReN-DEDC complex. In the present work, a solution to this problem was found by including an oxalate buffer of pH = 3 in vial 1, eliminating the need for the addition of glacial acetic acid by the user. This modification not only made the kits more user-friendly, it resulted in significant improvement in the kinetics of formation of [188ReN]2+ intermediate, wherein > 95% radiochemical purity could be achieved within 5 min incubation at ambient temperature. Moreover, the novel route for the preparation of [188ReN]2+ intermediate may be applied to any radiopharmaceutical based on 188ReN-core.

Accelerator-based production of the (99m)Tc-(186)Re diagnostic-therapeutic pair using metal disulfide targets (MoS2, WS2, OsS2).

Novel, natural abundance metal disulfide targets were irradiated for 1h with a 10µA proton beam in a small, medical cyclotron. Osmium disulfide was synthesized by simple distillation and precipitation methods while MoS2 and WS2 were commercially available. The targets dissolved under mild conditions and were analyzed by γ-spectroscopy. Production rates and potential applications are discussed, including target recovery and recycling schemes for OsS2 and WS2.

Synthesis of a novel organic-inorganic hybrid of polyaniline/titanium phosphate for Re(VII) removal.

The organic-inorganic hybrid material of polyaniline/titanium(IV) (PANI/Ti(HPO4)2) was synthesized by an oxidative polymerization reaction. The PANI/Ti(HPO4)2 was applied to remove Re(VII). The size of Ti(HPO4)2 nanoplates has no obvious effect on the sorption capacity. The effects of various environmental factors (such as pH, extra anions (NO3(-) and MO4(2-)) and temperature) on Re(VII) sorption to PANI/Ti(HPO4)2 were investigated by batch experiments. The sorption kinetics followed a pseudo-second-order model. The nitrogen-containing functional groups of PANI promoted Re(VII) sorption. The PANI/Ti(HPO4)2 exhibited excellent maximum sorption capacity to Re(VII) (47.62 mg g(-1)), which was superior to that of PANI (10.75 mg g(-1)) and much higher than that of many other sorbents. The sorption isotherms of Re(VII) can be well fitted with the Langmuir model. Re(VII) sorption decreased with increasing solution pH at pH > 4.0, which implied that Re(VII) sorption on PANI/Ti(HPO4)2 might be attributed to the outer-sphere complexation between amine and imine groups on the surface of PANI/Ti(HPO4)2 and Re(VII). This study implies that the hybrid material of PANI/Ti(HPO4)2 can be regarded as a potential sorbent to remove Re(VII) and its analogues from large volumes of aqueous solutions.

Production and separation of (186g)Re from proton bombardment of (186)WC.

A proof of concept study was undertaken where non-carrier added (186 g)Re was produced from the cyclotron bombardment of (186)WC. (186)WC was carbo-thermally generated from a novel precursor synthesized from (186)WO3, aqueous ammonia and hexamethyltetramine. The inherent high electrical and thermal conductivity of this material, coupled with its high melting point, made it an ideal candidate for proton bombardment for production of (186)Re. An18 µA irradiation for 3h and processing via thermo-chromatography, (186)WC yielded 0.93 mCi of (186 g)Re which corresponds to 89% of the calculated theoretical yields. The radiochemical purity of the desired (186 g)Re species was found to be between 95 and 97% with small contaminants of (186)ReO2. The radiochemistry utility of the product was investigated using S-benzoyl-MAG3, and 100% complexation was achieved with stability being maintained for 96 h. The re-oxidation of (186)WC back to(186)WO3 by oxygen in the thermo-chromatography method of processing ensured that the starting material was regenerated and recovered from the process in 94-98% yield.

Platinum and rhenium extraction from a spent refinery catalyst using Bacillus megaterium as a cyanogenic bacterium: statistical modeling and process optimization.

The present study evaluated the potential of Bacillus megaterium as a cyanogenic bacterium to produce cyanide for solubilization of platinum and rhenium from a spent refinery catalyst. Response surface methodology was applied to study the effects and interaction between two main effective parameters including initial glycine concentration and pulp density. Maximum Pt and Re recovery was obtained 15.7% and 98%, respectively, under optimum conditions of 12.8 g/l initial glycine concentration and 4% (w/v) pulp density after 7 days. Increasing the free cyanide concentration to 3.6 mg/l, varying the pH from 6.7 to 9, and increasing the dissolved oxygen from 2 to 5mg/l demonstrated the growth characteristics of B. megaterium during bioleaching process. The modified shrinking core model was used to determine the rate limiting step of the process. It was found that diffusion through the product layer is the rate controlling step.

Separation of no-carrier-added rhenium from bulk tantalum by the sodium malonate-PEG aqueous biphasic system.

The aqueous biphasic system (ABS) involving sodium malonate-polyethylene glycol (PEG) phases has been applied for the first time for separation of no-carrier-added (183)Re (T1/2=70 d) from α-particle irradiated bulk tantalum target. The various ABS conditions were applied for investigating the separation by varying pH, temperature, PEG-molecular weight, concentration of salt. The extraction pattern was hardly affected by change in pH and the molecular weight of PEG. One step separation of nca (183)Re from Ta was achieved at the optimal conditions of (i) 50% (w/w) PEG-4000-2 M sodium malonate, 40 °C and (ii) 50% (w/w) PEG-4000-3 M sodium malonate, room temperature (27 °C).

Contribution of tertiary amino groups to Re(VII) biosorption on modified corn stalk: competitiveness and regularity.

The effects of basic strength and steric hindrance of gels modified by dimethylamine, diethylamine, di-n-octylamine and di-2-ethylhexylamine, respectively, on rhenium (Re(VII)) adsorption capacity and selectivity were discussed. By comparing with the adsorption of other coexisting metals, such as Mo(VI), Cu(II), Pb(II), Fe(III), Zn(II), Mn(VII) and Ni(II), the gel modified by di-n-octylamine (DNOA-OCS) showed a high affinity for Re(VII) at higher hydrochloric acid concentration (C(H)(+)≥1.0 mol L(-1)), and the maximum adsorption capacity was 98.69 mg g(-1). This article not only described the adsorption behavior but also suggested isotherms, kinetics and thermodynamics of Re(VII) onto the DNOA-OCS gel in an aqueous medium using several models. Further study on adsorption of rhenium in a fixed-bed column packed with the DNOA-OCS gel under continuous and recirculating modes could confirm that the corn stalk gel modified by di-n-octylamine could be used as the adsorbent of Re(VII) from Mo-containing wastewater.

A new approach for rhenium(VII) recovery by using modified brown algae Laminaria japonica adsorbent.

Brown algae Laminaria japonica was chemically modified with sulfuric acid to obtain a crosslinked brown algae gel (CAS). The CAS gel showed a high affinity for Re(VII) comparing with other biomass gels, and the maximum adsorption capacity was evaluated as 37.20 mg g(-1) in case of pH 6, which could be explained by their different adsorption mechanisms. The adsorption equilibrium, kinetics and thermodynamic study for Re(VII) on the CAS gel was discussed in detail by the several models, such as Langmuir, Freundlich, Temkin and Dubinin-Radushkevich model for kinetics analysis, the pseudo first, the second-order, the Elovich and intraparticle diffusion equation for equilibrium analysis. Reutilization of the CAS gel was confirmed up to three adsorption-elution cycles in column-mode operation with no damage of gel, packed in the column. The result also provides a new approach for the recovery of Re(VII) from Re-containing wastewater by using the modified brown algae gel.

Rhenium-188: availability from the (188)W/(188)Re generator and status of current applications.

Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting ß(-) particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 keV, 15.1%). The (188)W/(188)Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) (188)Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent (188)W radionuclide have been a major impediment in the progress of application of (188)Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade (188)W/(188)Re generators. Since the specific activity of (188)W used in the generator is relatively low 185 GBq( < 5 Ci)/g], the eluted (188)ReO(4)(-) can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful (188)ReO(4)(-) solutions. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on (188)Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability and use of (188)Re including a discussion of why broader use of (188)Re has not progressed as expected as a popular radionuclide for therapy.

Immobilization, trapping, and anion exchange of perrhenate ion using copper-based tripodal complexes.

We describe a multidentate tripodal ligand in which three pendant arms carrying di(2-picolyl)amine units are linked to the ortho positions of a tris(o-xylyl) scaffold, providing N(CH(2)-o-C(6)H(4)CH(2)N(CH(2)py)(2))(3) (L). Reaction of L with CuCl(2) in the presence of hexafluorophosphate anion afforded blue cubes of [(CuCl)(3)L](PF(6))(3)·5H(2)O (1). Crystallographic studies of 1 revealed that the three symmetry-related arms each coordinate a {Cu(II)Cl} unit, and two molecules of 1 are connected to one another through a Cu(µ-Cl)(2)Cu bridge, extending the molecular structure to form a two-dimensional (2-D) layer. These 2-D layers pack in an ABCABC... fashion with PF(6)(-) anions located in between. Reaction of 1 with a stoichiometric amount of perrhenate ion afforded blue plates of [(CuCl)(3)L](PF(6))(ReO(4))(2)·3H(2)O (2). Compound 2 has the same lattice structure as 1, but the tricopper unit backbone now traps one ReO(4)(-) anion through Coulombic interactions. In addition, three molecules of 2 are bridged by a perrhenate ion, forming a Cu(3)(µ(3)-ReO(4)) cluster, to give a different 2-D structure displaying a rare tridentate bridging ReO(4)(-) mode. Thus, in addition to classic perrhenate trapping through weak Coulombic interactions, 2 represents an exceptional example in which the ReO(4)(-) anion is immobilized in an extended framework through tight covalent interactions. The interlamellar PF(6)(-) anions in 1 can be exchanged with other anions including perrhenate, perchlorate, or periodate. The structural similarity between perrhenate and pertechnetate makes these materials of potential interest for pertechnetate trapping.

Investigation on the removal of Mo(VI) from Mo-Re containing wastewater by chemically modified persimmon residua.

Persimmon waste was chemically modified by crosslinking with concentrated sulfuric acid to obtain a novel kind of adsorption gel, which was termed as crosslinked persimmon tannin (CPT), hereinafter. The adsorption behaviors of Mo(VI) with other coexisting metal ions onto the CPT gel were investigated. The gel exhibited selectivity only for Mo(VI) ions evidenced by the high value of separation factor of molybdenum and rhenium (ß(Mo/Re)=164.37), and the adsorption mechanism of Mo(VI) as a multispecies was studied. The molybdenum adsorption behavior conforms to the Langmuir model with a remarkably high adsorption capacity of 0.56 mol/kg. A kinetic study for the adsorption of molybdenum at various temperatures confirmed that the endothermic adsorption process followed pseudo-second order kinetics. Moreover, its excellent adsorption properties and applicability for Mo(VI) were demonstrated by the removal and separation of Mo(VI) from different Mo-Re containing industrial wastewaters.

Selective adsorption of molybdenum(VI) from Mo-Re bearing effluent by chemically modified astringent persimmon.

Astringent persimmon was chemically cross-linked by formaldehyde to obtain a novel kind of adsorption gel, which was named as APF gel. The adsorption behaviors of Mo(VI) and Re(VII) along with other coexisting metals onto the APF gel were studied in the present paper. The APF gel was found to be effective for the adsorption of Mo(VI) while the gel is almost completely inert toward rhenium and calcium over the whole hydrochloric acid concentration region. The APF gel has a low affinity for iron, copper, lead, nickel, manganese and zinc ions when the concentration of HCl is higher than 1 mol/L. The gel exhibited selectivity only for Mo(VI) with a remarkably high adsorption capacity 1.05 mol/kg, and the adsorption behavior obeys the Langmuir model. According to the thermodynamic and kinetic studies, the endothermic adsorption process followed pseudo-second order kinetics. Also, its excellent adsorption characteristics for Mo(VI) were confirmed by the adsorption and elution tests using a column packed with the APF gel. The result provides a new approach for the recovery of Mo(VI) from a industrial waste effluent.

Influence of rhenium speciation on the stability and activity of Re/Pd bimetal catalysts used for perchlorate reduction.

Recent work demonstrates reduction of aqueous perchlorate by hydrogen at ambient temperatures and pressures using a novel rhenium-palladium bimetal catalyst immobilized on activated carbon (Re/Pd-AC). This study examines the influence of Re speciation on catalyst activity and stability. Rates of perchlorate reduction are linearly dependent on Re content from 0-6 wt %, but no further increases are observed at higher Re contents. Surface-immobilized Re shows varying stability and speciation both in oxic versus H(2)-reducing environments and as a function of Re content. In oxic solutions, Re immobilization is dictated by sorption of the Re(VII) precursor, perrhenate (ReO(4)(-)), to activated carbon via electrostatic interactions. Under H(2)-reducing conditions, Re immobilization is significantly improved and leaching is minimized by ReO(4)(-) reduction to more reduced species on the catalyst surface. X-ray photoelectron spectroscopy shows two different Re binding energy states under H(2)-reducing conditions that correspond most closely to Re(V)/Re(IV) and Re(I) reference standards, respectively. The distribution of the two redox states varies with Re content, with the latter predominating at lower Re contents where catalyst activity is more strongly dependent on Re content. Results demonstrate that both lower Re contents and the maintenance of H(2)-reducing conditions are key elements in stabilizing the active Re surface species that are needed for sustained catalytic perchlorate treatment.

Nanocrystalline zirconia: a novel sorbent for the preparation of (188)W/(188)Re generator.

Nanocrystalline zirconia, a novel high capacity sorbent material was synthesized and tested for its utility in the preparation of (188)W/(188)Re generators. The structural investigation of the material was carried out using X-ray diffraction, surface area determination, FTIR and TEM micrograph analysis. Various experimental parameters were optimized to separate (188)Re from (188)W. The capacity of the material was found to be approximately 325mgW/g at the optimum pH. A chromatographic (188)W/(188)Re generator was developed using this material from which >80% of (188)Re generated could be eluted with 0.9% saline solution, with high radionuclidic, radiochemical and chemical purity and appreciably high radioactive concentration suitable for radiopharmaceutical applications.

Molecular recognition of pertechnetate and perrhenate.

This tutorial review covers the chemistry of artificial receptors designed to recognize the pertechnetate and perrhenate anions. It focuses on the molecular features that give rise to effective and selective complexation. Specific receptor classes are discussed in the context of available solution-phase and solid-state data with differences between pertechnetate and perrhenate binding behavior being highlighted where appropriate.

Development of a high performance (188)W/(188)Re generator by using a synthetic alumina.

A synthetic alumina functionalized with a sulfate moiety has been developed as the column material of (99)Mo/(99m)Tc and (188)W/(188)Re generators. This material is synthesized by a sol-gel processing. In order to characterize the adsorbent for the (188)W/(188)Re separation, both batch and column contact experiments were conducted. As a result of the experiments, it is found that the maximum capacity of the adsorbent for tungsten is higher than 450mg/g. Hence it is possible to produce approximately 3Ci (188)W/(188)Re generator with only 1g of the adsorbent from (188)W solutions supplied from ORNL, USA or RIAR, Russia. A demonstration study was conducted to show the performance of an (188)W/(188)Re generator column. In this study, 1Ci of (188)W purchased from RIAR, Russia, is loaded on a 0.9cm ID column packed with 0.7g of the adsorbent. Elution of (188)Re is performed every 4-7 days by using the saline solution for more than three months. Nearly 100% of tungsten is loaded by passing 5ml of the (188)W solution (pH=8) through the dry packed column at a 1ml/min flow rate. Elution efficiency of (188)Re is 70-90% by using 5ml of the saline solution. The ratio of (188)W/(188)Re in the eluted solution is 0.002-0.003%. When a Sep-Pak containing 0.26g of acid alumina is installed as a tandem column, the ratio is decreased to less than 10(-3)%. Thin layer chromatography for the eluted (188)Re solution shows 100% radiochemical purity. Also, alumina content in the eluted solution shows less than 10ppm. Through this study, the performance of this adsorbent was successfully demonstrated. By using the developed adsorbent, minimization of the generator column and consequently the volume of eluant could be possible while maintaining the quality of (188)Re just as much as that available in the market.

Uptake of Re(VII) from aqueous solutions by Bacillus sp. GT-83-23.

Thirty-eight water samples were collected from various areas of Anzali lagoon, Iran. Initial screening of a total of 100 bacterial isolates, resulted in the selection of one isolate with maximum adsorption capacity. It was tentatively identified as Bacillus sp. and named strain GT-83-23. The optimum pH of the medium was found to be 2.0 for Re(VII) adsorption. Uptakes of Re(VII) increased with increasing Re(VII) concentration and decreased sharply by the presence of increasing concentrations of NaCl. The kinetic of Re(VII) sorption by Bacillus sp. GT-83-23 was fast, reaching more than 62% of the total sorption capacity within 5 min. As the cell concentration increased, the amount of Re(VII) adsorbed by each cell (specific uptake) decreased, whereas the total amount of Re(VII) adsorbed enhanced. Cells immobilized in calcium alginate gel took up 77% of the Re(VII). The binding of Re(VII) on the Bacillus sp. GT-83-23 was studied with micro-PIXE.

Evaluation of two methods for concentrating perrhenate (188 Re) eluates obtained from 188 W-188 Re generator.

Two novel and simple methods for post-elution concentration (PEC) of (188)Re-perrhenate, using (i) a single diethyl amino ethyl (DEAE) cellulose anion exchanger column and (ii) a combination of Dowex-1 x 8 and AgCl columns, are described here. In the first system, 20-25 ml of (188)Re-perrhenate in acidic ammonium acetate was trapped in the small anion exchanger column of DEAE cellulose which was subsequently recovered in 4 ml of normal saline. In the second method, (188)Re-perrhenate eluate in 20-40 ml normal saline was trapped on a small strong base anion exchanger column, Dowex-1 x 8, and recovered in 5 ml of 0.2M NaI solution and finally processed over 1g AgCl column so as to obtain it in physiological saline solution in a final volume of 6.5 ml including 1.5 ml de-ionized water washings. In both the methods, the radiochemical purity of (188)Re-perrhenate was >98% and (188)W breakthrough was less than 10(-3)%.

A semi-automated system for concentration of rhenium-188 for radiopharmaceutical applications.

A semi-automated system has been designed and installed for the routine production of highly concentrated solutions of rhenium-188 perrhenate in saline which incorporates extensive radiation protection for the laboratory staff. This new system represents a simple, rapid, and effective computer controlled method using inexpensive disposable components. The flipper-valve settings and the radioactivity measured by use of collimated gamma dose rate probes are continuously monitored. If necessary, 2-3 tungsten-188/rhenium-188 generators can be eluted in a tandem arrangement. Eluate volumes (1.3-2 ml) of maximum specific radioactivity of 25 GBq/ml were routinely prepared.