Ga Generator Research Articles

Optimization of Automated Radiosynthesis of Gallium-68-Labeled PSMA11 with Two [68Ge]Ge/[68Ga]Ga Generators: Fractional Elution or Prepurification?

Prostate cancer is one of the most common forms of cancer in men. An imaging technique for its diagnosis is [68Ga]-prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) positron emission tomography (PET). To address the increasing demand for [68Ga]-labeled peptides and reduce the cost of radiosynthesis, it is therefore necessary to optimize the elution process of [68Ge]Ge/[68Ga]Ga generators. This study aims to identify the most effective approach for optimizing radiosynthesis using double elution in parallel of two [68Ge]Ge/[68Ga]Ga generators. Two methods have been tested: one using prepurification, and the other using fractionated elution. Five synthesis sequences were conducted using each method. The mean labeling yields for double elution with prepurification were 45.8 ± 29.4 (mean ± standard deviation) and none met the required criteria. The mean labeling yields for the fractionated double elution were 97.5 ± 1.9 (mean ± standard deviation) meeting the criteria, significantly superior to the prepurification method (p = 0.012), and similar to those of simple elution. This study showed that fractionated double elution from [68Ge]Ge/[68Ga]Ga generators produced a significantly higher labeling yield than double elution with prepurification, resulting in a larger activity recovered via radiosynthesis, thereby allowing more diagnostic tests to be performed.

Ga(III) pyridinecarboxylate complexes: potential analogues of the second generation of therapeutic Ga(III) complexes?

A series of novel Ga(III)—pyridine carboxylates ([Ga(Pic)3]·H2O (GaPic; HPic = picolinic acid), H3O[Ga(Dpic)2]·H2O (GaDpic; H2Dpic = dipicolinic acid), [Ga(Chel)(H2O)(OH)]2·4H2O (GaChel; H2Chel = chelidamic acid) and [Ga(Cldpic)(H2O)(OH)]2 (GaCldpic; H2Cldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-H2Dpic systems by potentiometry and 1H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)2]+ (logβ021 = 16.23(6)), [Ga(Pic)3] (logβ031 = 20.86(2)), [Ga(Dpic)2]− (logβ021 = 15.42(9)) and [Ga(Dpic)2(OH)]2− (logβ-121 = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale 1H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC50 (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant P. aeruginosa. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 μM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.Graphical abstract

Shape-stabilized low melting-point alloy/expanded graphite composite thermal pad with excellent chip heat dissipation performance

• A low melting point alloy/expanded graphite composite thermal pad is prepared. • The oxidation of the alloy is beneficial to its adsorption by expanded graphite. • The composite thermal pad possesses a high thermal conductivity of 26.94 W/m·K. • A very low thermal impedance of 0.42 K·cm 2 /W is achieved by the thermal pad. • The thermal pad shows higher heat dissipation efficiency than the commercial one. Thermal interface materials that possess high thermal conductivity and can reach low thermal impedance during service, are highly desirable for chip heat dissipation systems, especially when cooling high-power chips. Herein, a novel thermal pad was developed by combining low melting point alloy having metal-level thermal conductivity and liquid-like rheological property with expanded graphite possessing large pore volume and high thermal conductivity. Specifically, the alloy 62.5Ga21.5In16Sn was modified by the trace-oxidation method to obtain oxidized alloy, followed by adsorbing into expanded graphite and then molding and pressing to fabricate the thermal pad. It is found that the oxidation treatment resulted in the generation of refractory metal oxides Ga 2 O 3 and SnO 2 within the alloy, thereby preventing the leakage of the alloy from the composite thermal pad. Impressively, the optimal low melting point alloy/expanded graphite composite thermal pad, prepared at the oxidation duration of 24 min, expanded graphite mass fraction of 4 % and compact density of 3.125 g/cm 3 , reached a thermal conductivity of as high as 26.94 W/m·K and a thermal impedance of as low as 0.42 K·cm 2 /W, along with exhibiting a good shape-stability. More significantly, when employed into a simulative desktop CPU cooling system, this thermal pad exhibited 36.78 % higher cooling efficiency under the forced air convection, extended ten times in the time for the chip to reach the upper limit temperature (100 ℃) under the natural air cooling, and benefited to the chip to fight with the pulse-type instantaneous thermal shock, as compared to the commercial thermal pad. These excellent characteristics and good heat dissipation performance make the low melting point alloy/expanded graphite composite thermal pad show great potential for use in chip thermal management systems.

Comparison of three different methods in [68 Ga]Ga-PSMA11 radiolabeling.

In this study, quality control parameters such as radiochemical yield, radiochemical purity, and in vitro stability of gallium (68 Ga)-prostate-specific membrane antigen-11 ([68 Ga]Ga-PSMA11) radiopharmaceutical obtained in a research laboratory with three different synthesis algorithms were evaluated and compared. Gallium (68 Ga) chloride precursor to be used in labeling in all three methods was obtained by using ITG brand 68 Ge/68 Ga generator. The first method for the [68 Ga]Ga-PSMA11 radiopharmaceutical was performed with the automated synthesis module, which is widely used in clinical practice. Its radiochemical yield, quality assurance, and stability met expectations. Radiolabeling success, suitability of quality control parameters, and in vitro stability of [68 Ga]Ga-PSMA11 radiopharmaceutical performed with ANMI kit were examined. The final product showed success in 68 Ga-complexation kinetics. All quality control criteria performed met the expectation for clinical applications. Direct cold labeling of PSMA11 ligand with sodium bicarbonate buffer was examined. Results were similar to the ANMI kit. Considering that all three methods are successful in radiochemical labeling, labeling with NaHCO3 buffer shows the labeling preference when we choose the cheap, practical, and easy labeling option.

Multi-curie production of gallium-68 on a biomedical cyclotron and automated radiolabelling of PSMA-11 and DOTATATE

BackgroundWith increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([68Ge]Ge/[68Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie levels of [68Ga]GaCl3 from solid zinc-68 targets and subsequent labelling to produce clinical-grade [68Ga]Ga-PSMA-11 and [68Ga]Ga-DOTATATE.ResultsEnriched zinc-68 targets were irradiated at up to 80 µA with 13 MeV protons for 120 min; repeatedly producing up to 194 GBq (5.24 Ci) of purified gallium-68 in the form of [68Ga]GaCl3 at the end of purification (EOP) from an expected > 370 GBq (> 10 Ci) at end of bombardment. A fully automated dissolution/separation process was completed in 35 min. Isolated product was analysed according to the Ph. Eur. monograph for accelerator produced [68Ga]GaCl3 and found to comply with all specifications. In every instance, the radiochemical purity exceeded 99.9% and importantly, the radionuclidic purity was sufficient to allow for a shelf-life of up to 7 h based on this metric alone. Fully automated production of up to 72.2 GBq [68Ga]Ga-PSMA-11 was performed, providing a product with high radiochemical purity (> 98.2%) and very high apparent molar activities of up to 722 MBq/nmol. Further, manual radiolabelling of up to 3.2 GBq DOTATATE was performed in high yields (> 95%) and with apparent molar activities (9–25 MBq/nmol) sufficient for clinical use.ConclusionsWe have developed a high-yielding, automated method for the production of very high amounts of [68Ga]GaCl3, sufficient to supply proximal radiopharmacies. The reported method led to record-high purified gallium-68 activities (194 GBq at end of purification) and subsequent labelling of PSMA-11 and DOTATATE. The process was highly automated from irradiation through to formulation of the product, and as such comprised a high level of radiation protection. The quality control results obtained for both [68Ga]GaCl3 for radiolabelling and [68Ga]Ga-PSMA-11 are promising for clinical use.

Flexible transparent solar blind ultraviolet photodetector based on amorphous Ga<sub>2</sub>O<sub>3</sub> grown on mica substrate

Solar-blind deep-ultraviolet (UV) photodetectors (PDs) based on the super-wide bandgap semiconductor material Ga<sub>2</sub>O<sub>3</sub> is one of the hot topics of current research, but how to prepare high-performance Ga<sub>2</sub>O<sub>3</sub>-based solar-blind PDs in the field of flexible and transparent optoelectronics still faces challenges. In this work, an amorphous Ga<sub>2</sub>O<sub>3</sub> film with high transmittance is grown on a flexible mica substrate by using the radio frequency magnetron sputtering technology. On this basis, using AZO as an electrode material, a transparent metal-semiconductor-metal (MSM) structured solar-blind deep ultraviolet photodetector based amorphous Ga<sub>2</sub>O<sub>3</sub> film is fabricated, and the performance of PD in the planar state and after multiple bending are systematically compared and analyzed. The results show that the amorphous Ga<sub>2</sub>O<sub>3</sub> based transparent PD has ultra-high visible light transparency and shows good solar-blind ultraviolet photoelectric characteristics. The responsivity of the PD under 254 nm light is 2.69 A/W, and the response time and the recovery time are 0.14 s and 0.31 s, respectively. After bending 300 times, the PD has a photoresponse behavior similar to its planar state, and the performance of the PD has no obvious attenuation phenomenon, showing good flexibility and stability. This work proves that AZO can be used as the electrode material of the next generation of flexible and visible light transparent Ga<sub>2</sub>O<sub>3</sub> based photodetectors, and provides a reference for developing the high-performance flexible and transparent solar-blind deep ultraviolet photodetectors.

Revealing the Role of Liquid Metals at the Anode-Electrolyte Interface for All Solid-State Lithium-Ion Batteries.

All-solid-state lithium-ion batteries (ASSLIBs) are receiving tremendous attention for safety concerns over liquid system. However, current ASSLIBs still suffer from poor cycling and rate performance because of unfavorable interfacial contact between solid electrolyte and electrodes, especially in the alloy-based anode. To wet the solid electrode/electrolyte interface, accommodate volume change, and further boost kinetics, liquid metal Ga is introduced into the representative Sb anode, and its corresponding role is comprehensively revealed by experimental results and theoretical calculations for the first time. In addition to interface contact and strain accommodation, with the aid of in situ generation of liquid metal Ga, the lithiation/de-lithiation activity of Sb is stimulated, showing outstanding rate and cycling performance in half cells. Furthermore, benefited from the in situ chemical reaction, TiS2 powder can be directly used to construct a novel "Li-free" TiS2|LiBH4|GaSb full cell, which exhibits an outstanding capacity retention of 226 mA h g-1 after 1000 cycles at a current density of 0.5 A g-1. This work provides guidance for implementing future rational design of alloy anodes within ASSLIBs.

Structural and optical study of alternating layers of In and GaAs prepared by magnetron sputtering

Currently, the obtention of nano-structures based on III-V materials is expensive. This calls for novel and inexpensive nanostructure manufacturing approaches. In this work we report on the manufacture of a nanostructures consisting of alternating layers of In and GaAs on a silicon substrate by magnetron sputtering. Furthermore, we characterized the produced nanostructures using secondary ion mass spectroscopy (SIMS), X-ray diffraction analysis, and Raman spectroscopy. SIMS revealed variation in the concentration of In atoms across In/GaAs/In interphases, and X-ray diffraction revealed planes corresponding to phases associated with GaAs and InAs due to In interfacial diffusion across GaAs layers. Finally, in order to study the composition and crystalquality of the manufactured nanostaructures, Raman spectra were taken using laser excitation lines of 452 nm, 532 nm, and 562 nm at different points across the nanostructures.This allowed to determine the transverse and longitudinal optical modes of GaAs and InAs,characteristic of a two-mode behavior. An acoustic longitudinal vibrational mode LA(Γ) of GaAs and an acoustic longitudinal mode activated by disorder (DALA) were observed. These resulted from the substitution of Ga atoms for In atoms in high concentrations due to the generation of Ga(VGa) and/or Arsenic(VAs) vacancies.This set of analyses show that magnetron sputtering can be aviable and relatively low-cost technique to obtain this type of semiconductors.

Automated production of [68 Ga]Ga-DOTANOC and [68 Ga]Ga-PSMA-11 using a TRACERlab FXFN synthesis module.

The interest in gallium-68 labelled positron-emission tomography probes continues to increase around the world. However, one of the barriers for routine clinical use is the cost of the automated synthesis units for relatively simple labelling procedures. Herein, we describe the adaptation of a TRACERlab FXFN synthesis module for the automated production of gallium-68 radiopharmaceuticals using a cation-exchange cartridge for postprocessing of the 68 Ge/68 Ga generator eluate. The recovery of activity from the cartridge was 95.6% to 98.9% using solutions of acidified sodium chloride (5M with pH=1-3). The radiosyntheses of [68 Ga]Ga-DOTANOC and [68 Ga]Ga-PSMA-11 were performed using acetate sodium buffer or 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid, with a total duration of 21 and 23minutes, respectively, including generator elution and radiopharmaceutical dispensing. Activity yields were 77%±2% for [68 Ga]Ga-PSMA-11 and 68%±3% for [68 Ga]Ga-DOTANOC (n>100). The labelled peptides had a radiochemical purity exceeding 97%, and all quality control parameters were in conformity with the limits prescribed by the European Pharmacopoeia.

Efficient gallium-68 radiolabeling reaction of DOTA derivatives using a resonant-type microwave reactor.

Gallium-68 (68 Ga, t1/2 =68min) can be easily obtained from a 68 Ge/68 Ga generator, and several such systems are commercially available. The use of positron emission tomography (PET) imaging using 68 Ga-labeled radiopharmaceuticals is expected to increase in both preclinical and clinical settings. However, the chelation between a 68 Ga cation and the bifunctional macrocyclic chelates that are used for labeling bioactive substances, such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), requires a relatively long reaction time and high temperature to achieve a high radiochemical yield. Previously, we reported on a novel resonant-type microwave reactor that can be used for radiosynthesis and the usefulness of this reactor in the PET radiosynthesis of 18 F. In the present study, the usefulness of this resonant-type microwave reactor was evaluated for the radiolabeling of model macrocyclic chelates with 68 Ga. As a result, microwave heating of resonant-type microwave reactor notably improved the rate of the 68 Ga labeling chelate reaction in a short time period of 2minutes, compared with the use of a conventional heating method. Additionally, it was found that the use of this reactor made it possible to decrease the amount of precursors required in the reaction and to improve the molar activity of the labeled compounds.

Development of single vial kits for preparation of 68Ga‐labelled hexavalent lactoside for PET imaging of asialoglycoprotein receptor

The aim of this study was to formulate and evaluate the freeze-dried kit of NOTA-hexavalent lactoside (NOTA-HL) for the preparation of 68 Ga-labeled glycoligand for PET imaging of the asialoglycoprotein receptor (ASGPR). 68 GaCl3 was obtained from a commercial 68 Ge/68 Ga generator. Single-vial kits of HL were formulated. Optimization of radiolabeling with 68 Ga, various evaluations of NOTA-HL kits, and in vitro stability study of 68 Ga-HL were carried out. PET/CT imaging of normal mice injected with 68 Ga-NOTA-HL was performed. NOTA-HL kit was successfully formulated. High radiochemical yields (>95%) were obtained by 68 Ga radiolabeling. The NOTA-HL kits were stable for at least 12months, and 68 Ga-NOTA-HL exhibited good in vitro stability. PET studies in normal mice revealed high specific accumulation of activity in the liver. The NOTA-HL kit was developed for fast 68 Ga labeling. 68 Ga-NOTA-HL showed high specific uptake in liver. The availability of ready-to-use NOTA-HL kits combined with 68 Ge/68 Ga generators would provide an efficient approach for PET imaging of ASGPR.

An Automatic Filtering Method Based on an Improved Genetic Algorithm—With Application to Rolling Bearing Fault Signal Extraction

Fault feature extracted from fault signals plays a vital role in fault detection and diagnosis. However, in the early stage of defect, the fault signals (amplitudes and energy) are very weak and overwhelmed by large noise, and it is very difficult to extract fault feature effectively. To handle this problem, in this paper, an automatic filtering method based on an improved genetic algorithm (IGA) for extracting fault signals is presented. This method improves the binary coding generation of GA, so that each binary value matches a frequency of a fault signal frequency spectrum. Based on designed “statistical information evaluation function” as IGA fitness function, the similarity between normal state signal (noise signal) and IGA extracted noise signal is evaluated, and IGA employs genetic operations to search the optimal noise binary string. Negating noise binary string can obtain optimal fault signal binary string. It will then be multiplied by abnormal state vibration signal frequency spectrum, to yield a new frequency spectrum that only has fault components. This proposed method does not need to seek center frequency and bandwidth, and can automatically remove noise. The effective and advanced performance of the proposed method is evaluated by three different rolling bearing defects (outer race defect, inner race defect, and roller defect) in rolling bearing on rotating machine experimental bench and gearbox. Compared with rolling bearing fault characteristic frequency and results of denoising methods of bandpass filtering and wavelet decomposition, the proposed method can automatically filter noise and effectively extract fault signal. It proves that this method is feasible, effective, and advanced.

Equilibrium, Kinetic and Structural Properties of Gallium(III) and Some Divalent Metal Complexes Formed with the New DATAm and DATA5m Ligands.

The development of 68 Ge/68 Ga generators has made the positron-emitting 68 Ga isotope widely accessible and raised interest in new chelate complexes of Ga3+ . The hexadentate 1,4-di(acetate)-6-methyl[amino(methyl)acetate]perhydro-1,4-diazepane (DATAm ) ligand and its bifunctional analogue, 1,4-di(acetate)-6-pentanoic acid[amino(methyl)acetate]perhydro-1,4-diazepane (DATA5m ), rapidly form complexes with 68 Ga in high radiochemical yield. The stability constants of DATAm and DATA5m complexes formed with Ga3+ , Zn2+ , Cu2+ , Mn2+ and Ca2+ have been determined by using pH potentiometry, spectrophotometry (Cu2+ ) and 1 H and 71 Ga NMR spectroscopy (Ga3+ ). The stability constants of Ga(DATAm ) and Ga(DATA5m ) complexes are slightly higher than those of Ga(AAZTA). The species distribution calculations indicated the predominance of Ga(L)OH mixed-hydroxo complexes at physiological pH. The 1 H and 71 Ga NMR spectroscopy studies provided information about the coordinated functional groups of ligands and on the kinetics of exchange between the Ga(L) and Ga(L)OH complexes. The transmetalation reactions between the Ga(L) complexes and Cu2+ citrate (6<pH<8.5) occur through both spontaneous and OH- -assisted dissociation of the Ga(L)OH species. At pH 7.4 and 25 °C, the half-lives of the dissociation of Ga(DATAm ), Ga(DATA5m ) and Ga(AAZTA) were 11, 44 and 24 h, respectively. Similar half-lives have been obtained for the ligand-exchange reactions between the Ga(L)OH complexes and transferrin. The equilibrium and kinetic data indicate that the Ga(DATA5m ) complex is a good 68 Ga-based radiodiagnostic candidate.

Insights on hydride formation over cerium-gallium mixed oxides: A mechanistic study for efficient H2 dissociation

A four-step reaction mechanism is proposed for the H2 dissociation over pure ceria and gallium-promoted mixed oxide materials, in a combined experimental and computational investigation. Two samples of cerium-gallium mixed oxides with Ce/Ga atomic ratios equal to 90/10 and 80/20 were studied by time-resolved diffuse reflectance infrared spectroscopy under H2 (D2) flow at isothermal condition in the range of 523–623K. X-ray photoelectron spectrometry allowed to conclude that only Ce4+ is reduced to Ce3+ (Ga3+ is not reduced), in agreement with density functional theory (DFT) results. The time evolution profiles of gallium hydride (GaH) species, hydroxyl groups (OH) and Ce3+ infrared signals were analyzed and kinetic rate parameters for each step were obtained by mathematical modeling. The values for activation energies were in agreement with those calculated by DFT, for the different elementary pathways. A small activation energy (∼4kcal/mol) was found for H2 dissociation found on Ga⋯OCe sites assuming that the heterolytic cleavage of the HH bond is the rate determining step. On pure ceria, the experimental activation energy is ∼23kcal/mol, showing that the addition of Ga3+ cations boosts the splitting of H2. Interestingly, the reduction step of pure CeO2 surface domains seems to proceed via a CeH/OH pair intermediate, according to DFT calculations. Moreover, 71Ga NMR experiments indicate the possible presence of gallia nanodomains. It is proposed that the generation of Ga⋯OCe sites in the perimeter of such surface gallia nanodomains is responsible for the enhanced reactivity of the mixed materials. The key role of this new type of sites to improve the efficiency of relevant catalytic reactions such as selective alkyne hydrogenation and light alkane dehydrogenation is then analyzed.

A simple method for preparation of pure 68 Ga-acetate precursor for formulation of radiopharmaceuticals: Physicochemical characteristics of the 68 Ga eluate of the SnO2 based-68 Ge/68 Ga column generator.

Gallium-68 radioisotope is an excellent source in clinical positron emission tomography application due to its ease of availability from germanium-68 (68 Ge)/gallium-68 (68 Ga) generator having a shelf life of 1year. In this paper, a modified method for purification of the primary eluate of 68 Ge-68 Ga generator by using a small cation exchange resin (Dowex-50) column has been described. The breakthrough of 68 Ge before and after purification of 68 Ga eluate was 0.014% and 0.00027%, respectively. The average recovery yield of 68 Ga after purification was 84%±8.6% (SD, n=335). The results of the physiochemical studies confirmed that the 68 Ga-acetate obtained is suitable for labeling of radiopharmaceuticals.

Investigations on the Ga(III) Complex of EOB-DTPA and Its 68Ga Radiolabeled Analogue.

We demonstrate a method for the isolation of EOB-DTPA (3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(ethoxybenzyl)-undecanedioic acid) from its Gd(III) complex and protocols for the preparation of its novel non-radioactive, i.e., natural Ga(III) as well as radioactive (68)Ga complex. The ligand as well as the Ga(III) complex were characterized by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry and elemental analysis. (68)Ga was obtained by a standard elution method from a (68)Ge/(68)Ga generator. Experiments to evaluate the (68)Ga-labeling efficiency of EOB-DTPA at pH 3.8-4.0 were performed. Established analysis techniques radio TLC (thin layer chromatography) and radio HPLC (high performance liquid chromatography) were used to determine the radiochemical purity of the tracer. As a first investigation of the (68)Ga tracers' lipophilicity the n-octanol/water distribution coefficient of (68)Ga species present in a pH 7.4 solution was determined by an extraction method. In vitro stability measurements of the tracer in various media at physiological pH were performed, revealing different rates of decomposition.

Comprehensive Quality Control of the ITG 68Ge/68Ga Generator and Synthesis of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC for Clinical Imaging.

A good-manufacturing-practices (GMP) (68)Ge/(68)Ga generator that uses modified dodecyl-3,4,5-trihydroxybenzoate hydrophobically bound to a octadecyl silica resin (C-18) as an adsorbent has been developed that allows for dilute HCl (0.05N) to efficiently elute metal-impurity-free (68)Ga(3+) ready for peptide labeling. We characterized the performance of this generator system over a year in conjunction with the production of (68)Ga-labeled DOTATOC and Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (PSMA-HBED-CC) intended for clinical studies and established protocols for batch release. A 2,040-MBq self-shielded (68)Ge/(68)Ga generator provided metal-free (68)GaCl3 ready for peptide labeling in the fluidic labeling module after elution with 4 mL of 0.05N HCl. The compact system was readily housed in a laminar flow cabinet allowing an ISO class-5 environment. (68)Ga labeling of peptides using GMP kits was performed in 15-20 min, and the total production time was 45-50 min. Batch release quality control specifications were established to meet investigational new drug submission and institutional review board approval standards. Over a period of 12 mo, (68)Ga elution yields from the generator averaged 80% (range, 72.0%-95.1%), and (68)Ge breakthrough was less than 0.006%, initially decreasing with time to 0.001% (expressed as percentage of (68)Ge activity present in the generator at the time of elution), a unique characteristic of this generator. The radiochemical purity of both (68)Ga-DOTATOC and (68)Ga-PSMA-HBED-CC determined by high-performance liquid chromatography analysis was greater than 98%, with a minimum specific activity of 12.6 and 42 GBq/μmol, respectively. The radionuclidic ((68)Ge) impurity was 0.00001% or less (under the detection limit). Final sterile, pyrogen-free formulation was provided in physiologic saline with 5%-7% ethanol. The GMP-certified (68)Ge/(68)Ga generator system was studied for a year. The generator system is contained within the fluidic labeling module, and it is compact, self-shielded, and easy to operate using simple manual techniques. The system provides radiolabeled peptides with high (>98%) radiochemical purity and greater than 80% radiochemical yield. The (68)Ge levels in the final drug products were under the detection limits at all times. (68)Ga-DOTATOC and (68)Ga-PSMA-HBED-CC investigational radiopharmaceuticals are currently being studied clinically under investigational new drug (IND) applications submitted to the U.S. Food and Drug Administration.

A novel, self-shielded modular radiosynthesis system for fully automated preparation of PET and therapeutic radiopharmaceuticals.

With the vast development of theranostics and, recently, (68)Ga-radiolabeled molecules, there is also a need for novel, smaller, flexible, safe, and efficient modular automated synthesis systems in different clinical settings. The aim of our study was to determine the shielding properties of the modular self-shielded automated radiosynthesis box and determine its suitability for routine preparation of different radiopharmaceuticals to be used for diagnosis and therapy. To evaluate shielding properties, shielding factors were determined using two different radiation sources: (137)Cs and (68)Ga. The dose rates were measured at critical points at the surface and 1 m distance from the surface. Three different methods were used to concentrate and purify (68)Ga generator eluate. Performance of the system was tested by evaluating several radiolabeling applications using (68)Ga, (177)Lu, and (90)Y. Dose rates measured at the surface did not exceed 9 μSv/h for (68)Ga and 20 μSv/h when using (137)Cs. On average, dose rates at the surface were reduced for factors of 1665 and 906, respectively. Different DOTA peptides were labeled successfully with (68)Ga with radiochemical purities more than 94% using three different radiolabeling methods. (177)Lu-DOTATATE and (90)Y-DOTATATE were synthesized reproducibly with a radiochemical purity of more than 99% and more than 97%, respectively. A self-shielded radiosynthesis box is a unique solution for nuclear medicine departments that lack space for installation of standard automated synthesis systems set in large and heavy dedicated PET synthesis boxes. Shielding properties are sufficient for safe clinical use for both PET and β(-) radioisotopes. Because of its modular design and the simple adaptability of system parameters, the system can be used for the preparation of different clinically used radiopharmaceuticals and is also useful for research purposes.

A new (68)Ga anionic concentration and purification method for automated synthesis of [(68)Ga]-DOTA or NODAGA conjugated peptides in high radiochemical purity.

The (68)Ge/(68)Ga generator is of increasing interest for clinical PET. For successful labelling, the eluate has to be purified. The aim of our approach is to improve the existing anionic methods which have a number of advantages compared to other methods but which use high concentrated HCl, and require an additional anionizing step. A new (68)Ga-eluate anionic purification method that enables rapid and high efficiency labelling of DOTA and NODAGA conjugated peptides in high radiochemical purity is described. The new method uses NaCl as an alternative Cl(-) source to the corrosive HCl and combines the three standard steps in a single step. The recovery yield was ≥90%, and the (68)Ge breakthrough was in conformity with the European Pharmacopeia limit. An automated labelling of DOTA and NODAGA-conjugated peptides was performed with the new method, using acetate sodium buffer, with a total duration of 13 min and a radiochemical yield >85%. The labelled peptides have a radiochemical purity exceeding 99% and can be used directly without any further purification step and without the quality control by gas chromatography. Furthermore, the new method has an economic advantage: it offers the possibility to use generator until 20 months after the calibration date.

An improved genetic algorithm and its applications to the optimisation design of an aspirated compressor profile

SummaryGenetic algorithm (GA) is a widely used method for numerical optimisation owing to their good global search ability; however, their local search ability has an obvious shortcoming. To improve local search ability, this paper introduces a simplex method and combines it with a GA to form an improved genetic algorithm (IGA). In the IGA, at each generation of the original GA, high‐fitness individuals are selected as vertices of a simplex, and then a one‐dimensional search within the simplex is conducted to obtain the most‐fit individuals while replacing the inferior ones. Typical test functions show that the IGA can effectively improve the optimisation effect over that of the original GA. To further verify the IGA's practicability, an aspirated compressor profile is optimised with profile, suction flow rate and suction flow location as coupled design parameters. The results again show that the IGA has a better optimising effect than the GA. In addition, it is also verified that coupling the profile and suction flow parameters results in a design that outperforms the uncoupled design; therefore, designing an aspirated compressor blade by arranging suction flow on a conventional blade without considering suction flow is not a good method. Copyright © 2015 John Wiley &amp; Sons, Ltd.