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1.
J Radiol Prot ; 42(2)2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35705062

RESUMO

In this work, we conducted experiments to validate the proton physics models of Geant4 (version 10.6). The stopping power ratios (SPRs) of 11 inserts, such as acrylic, delrin, high density polyethylene, and polytetrafluoroethylene, etc, were measured using a superconducting synchrocyclotron that produces a scattering proton beam. The SPRs of the inserts were also calculated based on Geant4 simulation with six physics lists, i.e. QGSP_ FTFP_ BERT, QGSP_BIC_HP, QGSP_BIC, QGSP_FTFP_BERT, QSGP_BERT, and QBBC. The calculated SPRs were compared to the experimental SPRs, and relative per cent error was used to quantify the accuracy of the simulated SPRs of inserts. The comparison showed that the five physics lists generally agree well with the experimental SPRs with a relative difference of less than 1%. The lowest overall percentage error was observed for QGSP_FTFP_BERT and the highest overall percentage error was observed for QGSP_BIC_HP. The 0.1 mm range cut value consistently led to higher percentage error for all physics lists except for QGSP_BIC_HP and QBBC. Based on the validation, we recommend QGSP_BERT_HP physics list for proton dose calculation.


Assuntos
Terapia com Prótons , Prótons , Ciclotrons , Método de Monte Carlo , Física
2.
J Am Soc Mass Spectrom ; 33(8): 1499-1509, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35763614

RESUMO

The fine structure of isotopic peak distributions of glutathione in mass spectra is measured using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) at 12 and 15 T magnetic field, with an infinity cell and a dynamically harmonized cell (DHC) respectively. The resolved peaks in the fine structure of glutathione consist of 2H, 13C, 15N, 17O, 18O, 33S, 34S, 36S, and combinations of them. The positions of the measured fine structure peaks agree with the simulated isotopic distributions with the mass error less than 250 ppb in broadband mode for the infinity cell and no more than 125 ppb with the DHC after internal calibration. The 15 T FT-ICR MS with DHC cell also resolved around 30 isotopic peaks in broadband with a resolving power (RP) of 2 M. In narrowband (m/z 307-313), our current highest RP of 13.9 M in magnitude mode was observed with a 36 s transient length by the 15 T FT-ICR MS with the DHC and 2ω detection on the 15 T offers slightly higher RP (14.8 M) in only 18 s. For the 12 T FT-ICR MS with the infinity cell, the highest RP achieved was 15.6 M in magnitude mode with a transient length of 45 s. Peak decay was observed for low abundance peaks, which could be due to the suppression effects from the most abundant peak, as result of ion cloud Coulombic interactions (space-charge).


Assuntos
Ciclotrons , Glutationa , Calibragem , Análise de Fourier , Espectrometria de Massas/métodos
3.
J Am Soc Mass Spectrom ; 33(7): 1194-1203, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35709480

RESUMO

Formulated lubricants correspond to high value products used for several applications in automotive, industrial, medicinal, and agro-food sectors. They correspond to complex matrices composed of approximately 80% of base oils (mineral or synthetic) and of about 20% of additives. Additives are generally low molecular weight polymeric molecules with a great diversity of elements. To characterize such complex compositions at the molecular level, ultrahigh resolution mass spectrometers are required. Two formulated lubricants and two additive packages were analyzed by Fourier transform ion cyclotron resonance mass spectrometry in direct infusion. Atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) sources were used to have an exhaustive characterization of the samples. The Kendrick mass defects (KMD) plot is a widespread representation to characterize polymeric molecules. Here, the terms apparent mass defect and apparent Kendrick mass defects (aKMD) values were introduced to consider the uncertainty on nominal mass determination. Several additive families including alkyldiphenylamines, trisalkylphenylthiophosphoric acid, zinc dithiophosphates, bisuccinimide dispersants, and their derivatives were observed by APCI(+). ESI(-) also presented a use for the selective ionization of acidic compounds including sulfonates, phenates, and sulfur phenate molecules. The specific aKMD values and polydispersity of many additive families have been reported to create a database of additives. Overall, this study demonstrated the great utility of the aKMD approach and the use of the ESI/APCI combination for a simple and fast characterization of formulated lubricant and additive package samples.


Assuntos
Ciclotrons , Espectrometria de Massas por Ionização por Electrospray , Cefotaxima , Análise de Fourier , Humanos , Lubrificantes , Espectrometria de Massas por Ionização por Electrospray/métodos
4.
Radiat Oncol ; 17(1): 87, 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525993

RESUMO

BACKGROUND: A new compact superconducting synchrocyclotron single-room proton solution delivers pulsed proton beams to each spot through several irradiation bursts calculated by an iterative layer delivery algorithm. Such a mechanism results in a new beam parameter, burst switching time (BST) in the total beam delivery time (BDT) which has never been studied before. In this study, we propose an experimental approach to build an accurate BDT and sequence prediction model for this new proton solution. METHODS: Test fields and clinical treatment plans were used to investigate each beam delivery parameter that impacted BDT. The machine delivery log files were retrospectively analyzed to quantitatively model energy layer switching time (ELST), spot switching time (SSWT), spot spill time (SSPT), and BST. A total of 102 clinical IMPT treatment fields' log files were processed to validate the accuracy of the BDT prediction model in comparison with the result from the current commercial system. Interplay effect is also investigated as a clinical application by comparing this new delivery system model with a conventional cyclotron accelerator model. RESULTS: The study finds that BST depends on the amount of data to be transmitted between two sequential radiation bursts, including a machine irradiation log file of the previous burst and a command file to instruct the proton system to deliver the next burst. The 102 clinical treatment fields showed that the accuracy of each component of the BDT matches well between machine log files and BDT prediction model. More specifically, the difference of ELST, SSWT, SSPT, and BST were (- 3.1 ± 5.7)%, (5.9 ± 3.9)%, (2.6 ± 8.7)%, and (- 2.3 ± 5.3)%, respectively. The average total BDT was about (2.1 ± 3.0)% difference compared to the treatment log files, which was significantly improved from the current commercial proton system prediction (58 ± 15)%. Compared to the conventional cyclotron system, the burst technique from synchrocyclotron effectively reduced the interplay effect in mobile tumor treatment. CONCLUSION: An accurate BDT and sequence prediction model was established for this new clinical compact superconducting synchrocyclotron single-room proton solution. Its application could help users of similar facilities better assess the interplay effect and estimate daily patient treatment throughput.


Assuntos
Terapia com Prótons , Ciclotrons , Humanos , Terapia com Prótons/métodos , Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos
5.
J Am Soc Mass Spectrom ; 33(7): 1126-1133, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35604791

RESUMO

Collisionally activated dissociation (CAD), infrared multiphoton dissociation (IRMPD), ultraviolet photodissociation (UVPD), electron capture dissociation and electron detachment dissociation (EDD) experiments were conducted on a set of phosphopeptides, in a Fourier transform ion cyclotron resonance mass spectrometer. The fragmentation patterns were compared and varied according to the fragmentation mechanisms and the composition of the peptides. CAD and IRMPD produced similar fragmentation profiles of the phosphopeptides, while UVPD produced a large number of complementary fragments. Electron-based dissociation techniques displayed lower fragmentation efficiencies, despite retaining the labile phosphate group, and drastically different fragmentation profiles. EDD produced complex spectra whose interpretation proved challenging.


Assuntos
Fosfopeptídeos , Espectrometria de Massas em Tandem , Ciclotrons , Elétrons , Análise de Fourier , Fosfopeptídeos/química , Espectrometria de Massas em Tandem/métodos
6.
J Am Soc Mass Spectrom ; 33(6): 1022-1030, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35561028

RESUMO

Vitamin D compounds are a group of secosteroids derived from cholesterol that are vital for maintaining bone health in humans. Recent studies have shown extraskeletal effects of vitamin D, involving vitamin D metabolites such as the dihydroxylated vitamin D3 compounds 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3. Differentiation and characterization of these isomers by mass spectrometry can be challenging due to the zero-mass difference and minor structural differences between them. The isomers usually require separation by liquid chromatography (LC) prior to mass spectrometry, which adds extra complexity to the analysis. Herein, we investigated and revisited the use of fragmentation methods such as collisional induced dissociation (CID), infrared multiphoton dissociation (IRMPD), electron induced dissociation (EID), and ultraviolet photodissociation (UVPD), available on a 12T Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) to generate characteristic fragments for the dihydroxylated vitamin D3 isomers that can be used to distinguish between them. Isomer-specific fragments were observed for the 1,25-dihydroxyvitamin D3, which were clearly absent in the 24,25-dihydroxyvitamin D3 MS/MS spectra using all fragmentation methods mentioned above. The fragments generated due to cleavage of the C-6/C-7 bond in the 1,25-dihydroxyvitamin D3 compound demonstrate that the fragile OH groups were retained during fragmentation, thus enabling differentiation between the two dihydroxylated vitamin D3 isomers without the need for prior chromatographic separation or derivatization.


Assuntos
Colecalciferol , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Ciclotrons , Humanos , Espectrometria de Massas em Tandem/métodos , Vitamina D , Vitaminas
7.
Anal Chem ; 94(26): 9316-9326, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35604839

RESUMO

MALDI mass spectrometry imaging (MALDI MSI) is a powerful analytical method for achieving 2D localization of compounds from thin sections of typically but not exclusively biological samples. The dynamically harmonized ICR cell (ParaCell) was recently introduced to achieve extreme spectral resolution capable of providing the isotopic fine structure of ions detected in complex samples. The latest improvement in the ICR technology also includes 2ω detection, which significantly reduces the transient time while preserving the nominal mass resolving power of the ICR cell. High-resolution MS images acquired on FT-ICR instruments equipped with 7T and 9.4T superconducting magnets and the dynamically harmonized ICR cell operating at suboptimal parameters suffered severely from the pixel-to-pixel shifting of m/z peaks due to space-charge effects. The resulting profile average mass spectra have depreciated mass measurement accuracy and mass resolving power under the instrument specifications that affect the confidence level of the identified ions. Here, we propose an analytical workflow based on the monitoring of the total ion current to restrain the pixel-to-pixel m/z shift. Adjustment of the laser parameters is proposed to maintain high spectral resolution and mass accuracy measurement within the instrument specifications during MSI analyses. The optimized method has been successfully employed in replicates to perform high-quality MALDI MS images at resolving power (FWHM) above 1,000,000 in the lipid mass range across the whole image for superconducting magnets of 7T and 9.4T using 1 and 2ω detection. Our data also compare favorably with MALDI MSI experiments performed on higher-magnetic-field superconducting magnets, including the 21T MALDI FT-ICR prototype instrument of the NHMFL group at Tallahassee, Florida.


Assuntos
Ciclotrons , Diagnóstico por Imagem , Análise de Fourier , Íons , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
8.
Appl Radiat Isot ; 186: 110252, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35537298

RESUMO

The future development of personalized nuclear medicine relies on the availability of novel medical radionuclides. In particular, radiometals are attracting considerable interest since they can be used to label both proteins and peptides. Among them, the ß+-emitter 68Ga is widely used in nuclear medicine for positron emission tomography (PET). It is used in theranostics as the diagnostic partner of the therapeutic ß--emitters 177Lu and 90Y for the treatment of a wide range of diseases, including prostate cancer. Currently, 68Ga is usually obtained via 68Ge/68Ga generators. However, their availability, high price and limited produced radioactivity per elution are a major barrier for a wider use of the 68Ga-based diagnostic radiotracers. A promising solution is the production of 68Ga by means of proton irradiation of enriched 68Zn liquid or solid targets. Along this line, a research program is ongoing at the Bern medical cyclotron, equipped with a solid target station. In this paper, we report on the measurements of 68Ga, 67Ga and 66Ga production cross-sections using natural Zn and enriched 68Zn material, which served as the basis to perform optimized 68Ga production tests with enriched 68Zn solid targets.


Assuntos
Ciclotrons , Neoplasias da Próstata , Radioisótopos de Gálio/metabolismo , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioisótopos , Compostos Radiofarmacêuticos/metabolismo
9.
Appl Radiat Isot ; 186: 110287, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35597156

RESUMO

In the last years, 155Tb has attracted enormous interest due to its potential role in theranostics in nuclear medicine. To estimate its production yield, the aim of this study was to develop a method to prepare thin Gd-enriched-containing targets aimed at the 155Gd(d, 2n)155Tb nuclear cross section measurement. To this end, the electrochemical co-deposition method has been chosen to manufacture Ni-Gd2O3 composite targets. Several process parameters that have an impact on the deposit quality, have been investigated to increase the incorporation of Gd mass (up to 3 mg). To validate the concept, seven targets made by natural Gd were irradiated with deuteron beams at the GIP ARRONAX facility cyclotron, with an energy range ranging from 8 MeV to 30 MeV to extract the cross section values by using the stacked-foils method. Results obtained turned out to have great consistency with existing published data thus validating the proposed method. Therefore, an alternative target manufacturing concept aimed at cross section measurement is presented in this work.


Assuntos
Ciclotrons
10.
Med Phys ; 49(7): 4875-4911, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35403262

RESUMO

Higher dose rates, a trend for radiotherapy machines, can be beneficial in shortening treatment times for radiosurgery and mitigating the effects of motion. Recently, even higher doses (e.g., 100 times greater) have become targeted because of their potential to generate the FLASH effect (FE). We refer to these physical dose rates as ultra-high (UHDR). The complete relationship between UHDR and the FE is unknown. But UHDR systems are needed to explore the relationship further and to deliver clinical UHDR treatments, where indicated. Despite the challenging set of unknowns, the authors seek to make reasonable assumptions to probe how existing and developing technology can address the UHDR conditions needed to provide beam generation capable of producing the FE in preclinical and clinical applications. As a preface, this paper discusses the known and unknown relationships between UHDR and the FE. Based on these, different accelerator and ionizing radiation types are then discussed regarding the relevant UHDR needs. The details of UHDR beam production are discussed for existing and potential future systems such as linacs, cyclotrons, synchrotrons, synchrocyclotrons, and laser accelerators. In addition, various UHDR delivery mechanisms are discussed, along with required developments in beam diagnostics and dose control systems.


Assuntos
Radioterapia (Especialidade) , Radiocirurgia , Ciclotrons , Aceleradores de Partículas , Dosagem Radioterapêutica , Síncrotrons
11.
Rev Sci Instrum ; 93(3): 033302, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35364983

RESUMO

This paper reviews the main microwave diagnostic techniques and tools adopted in electron cyclotron resonance (ECR) (and others) ion source laboratories, with a special focus on techniques and instruments developed at INFN-LNS. Along with the tools used for optimization of microwave launching (power monitors, spectral analysis, and network analyzers), this paper deals, in particular, with more recent devices on-purpose developed to perform in-plasma analysis, such as absolute density measurements and density profiles retrieval. Among these, the first example of microwave interferometry for ECR compact machines (the VESPRI interferometer at INFN-LNS) will be briefly discussed, in combination with microwave polarimetric techniques based on Faraday rotation detection. More sophisticated microwave techniques are going to be designed and are now at a numerical study stage, e.g., profilometry and imaging via inverse scattering methods (this paper will offer short theoretical bases and first numerical results on 1D profilometry). In the end, the relevance about the implications and interplays of microwave techniques in multidiagnostic systems (microwave, optical, and x-ray domains) will be commented, with a special focus on time resolved microwave measurements and advanced signal processing via wavelet transform, useful for characterization of plasma instabilities.


Assuntos
Ciclotrons , Elétrons , Micro-Ondas , Vibração
12.
Sensors (Basel) ; 22(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35408196

RESUMO

A CS-30 cyclotron has been in operation at King Faisal Specialist Hospital and Research Center (KFSHRC) since 1982. The CS-30 cyclotron has been used to produce medical radioisotopes for positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Some of the nuclear reactions of radionuclide production are associated with the intense release of a wide range of fast neutrons. In this work, we investigated the radionuclides produced from neutron interactions with the cyclotron facility walls. Activation isotopes were determined by performing gamma ray spectrometry utilizing a high-purity germanium (HPGe) detector. The major radionuclides found were 152Eu, 154Eu, 134Cs, 65Zn and 60Co. Activation isotope accumulation had increased the dose rate inside the facility. The surface dose rates were measured at all of the surrounding walls. The maximum surface dose rate was found to be 1.2 µSv/h, which is much lower than the permissible occupational exposure of 15 µSv/h based daily 5 work hours.


Assuntos
Ciclotrons , Exposição Ocupacional , Nêutrons , Exposição Ocupacional/análise , Tomografia por Emissão de Pósitrons , Radioisótopos
13.
Food Chem ; 388: 132998, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35453011

RESUMO

An in vivo microcapillary sampling (MCS) method coupled with matrix-assisted laser desorption/ionization fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS) analysis was utilized to monitor the real-time bipyridine quaternary ammonium herbicides concentrations and assess their uptake and elimination behaviors in living cabbage plants noninvasively. Under optimized conditions, the proposed method for paraquat (PQ) and diquat (DQ) determination showed wide linear ranges (7.81-500 µg/kg), low limits of detection (0.1-0.9 µg/kg), and good reproducibility. In vivo tracking results demonstrated that different absorption behaviors between PQ and DQ existed in living vegetables and DQ was more easily absorbed. Through decay kinetics model fitting, herbicide half-lives were 1.32 and 1.86 days for PQ and DQ, respectively. To summarize, in vivo MCS method provides valuable information on herbicide risks for agricultural production, which is suitable for temporal, spatial, and longitudinal studies in the same living system and multicompartmental studies in the same organism.


Assuntos
Diquat , Herbicidas , Ciclotrons , Diquat/análise , Análise de Fourier , Herbicidas/análise , Lasers , Paraquat/análise , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Verduras
14.
Nucl Med Biol ; 110-111: 59-66, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35487834

RESUMO

Lanthanum radiometals are well positioned to serve as theranostic PET radiometals for targeted radionuclide therapy. The positron emitters 132La and 133La show promise to serve as unique PET imaging agents for 225Ac targeted alpha-particle therapy, the 134Ce/134La pair has PET imaging potential with both 225Ac and 227Th, and 135La has potential in targeted Auger-Meitner electron therapy. With easily accessible cyclotron production routes, effective and efficient chemical separations, and robust chelation chemistry, these radionuclides are well poised for additional preclinical and clinical PET and targeted radionuclide therapy studies. This review summarizes recent advances in radiolanthanum production and preclinical applications that demonstrate the strong potential of these radionuclides in PET and targeted radionuclide therapy.


Assuntos
Medicina de Precisão , Radioisótopos , Partículas alfa/uso terapêutico , Ciclotrons , Tomografia por Emissão de Pósitrons , Radioisótopos/uso terapêutico
15.
Appl Radiat Isot ; 184: 110117, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35272232

RESUMO

A low cost and easily implemented target system for neutron activation was developed that takes advantage of the neutron flux produced as a by-product during the cyclotron production of medical isotopes. Samples are placed in close proximity to an 18O(p,n)18F target on a cyclotron operating between 18 and 22 MeV for irradiation. Analysis of the samples by gamma spectroscopy shows that activation is proportional to the neutron exposure, and the mass of the element present in the sample.


Assuntos
Ciclotrons , Ouro , Raios gama , Nêutrons , Prata
16.
Appl Radiat Isot ; 184: 110190, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35303628

RESUMO

A new proton beam-line dedicated to R&D programs has been developed at CentreAntoine Lacassagne (CAL), in Nice (France), in collaboration with the Centrenational d'études spatiales (CNES). This is the second beam-line of the MEDICYC 65 MeV cyclotron that is currently in operation, the first being the clinical 'eye-line' used for ocular proton therapy. The R&D beam-line is proposed with two configurations, the first producing a Gaussian narrow beam of a few mm width, the second a 100 mm diameter flat beam with a homogeneity better than ±3%. The energy range is (20 - ∼60) MeV, where the exact upper limit depends on the beam configuration being used. The energy spread of the non-degraded beam is (0.3 ± 0.1) MeV. A beam current between 10 pA and 10 µA can be produced with a stability better than 0.2% above 100 pA, and 2% below. The beam can be monitored online at a precision better than 5% in the flux range 1E5 (1E6) - 1E9 (1E10) p/cm2/s for a flat (Gaussian) configuration, although work is in progress to extend this range. Targeted applications for the R&D beam-line are instrumentation research, radiation tolerance tests of components and radiobiology.


Assuntos
Terapia com Prótons , Prótons , Ciclotrons , Terapia com Prótons/métodos , Radiobiologia , Dosagem Radioterapêutica , Pesquisa
17.
Anal Chem ; 94(13): 5335-5343, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35324161

RESUMO

Mass spectrometry imaging (MSI) allows for untargeted mapping of the chemical composition of tissues with attomole detection limits. MSI using Fourier transform (FT)-based mass spectrometers, such as FT-ion cyclotron resonance (FT-ICR), grants the ability to examine the chemical space with unmatched mass resolution and mass accuracy. However, direct imaging of large tissue samples using FT-ICR is slow. In this work, we present an approach that combines the subspace modeling of ICR temporal signals with compressed sensing to accelerate high-resolution FT-ICR MSI. A joint subspace and spatial sparsity constrained model computationally reconstructs high-resolution MSI data from the sparsely sampled transients with reduced duration, allowing a significant reduction in imaging time. Simulation studies and experimental implementation of the proposed method in investigation of brain tissues demonstrate a 10-fold enhancement in throughput of FT-ICR MSI, without the need for instrumental or hardware modifications.


Assuntos
Ciclotrons , Diagnóstico por Imagem , Análise de Fourier , Espectrometria de Massas/métodos
18.
Appl Radiat Isot ; 184: 110175, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35344829

RESUMO

155Tb [t1/2 = 5.32 d, Eγ = 87 keV (32%); 105 keV (25%) (IAEA, 2021)] is a novel promising radionuclide for theranostic applications in nuclear medicine. Its physical properties make it suitable for single photon emission computed tomography (SPECT) imaging, while its chemistry allows it to be used as a diagnostic partner for therapeutic radiolanthanides or pseudo-radiolanthanides, such as 177Lu and 90Y. Moreover, 155Tb could be used as a precise diagnostic match for the ß--emitter 161Tb, opening doors for the true theranostics concept. The availability of 155Tb in quantity and quality suitable for medical applications is an open issue and its production with medical cyclotrons via the 155Gd(p,n)155Tb and 156Gd(p,2n)155Tb nuclear reactions represents a possible but challenging solution. For this purpose, an accurate knowledge of the production cross sections is mandatory. In this paper, we report on the measurement of the production cross sections of 155Tb and other terbium radionuclides formed by proton irradiation of natGd2O3, 155Gd2O3 and 156Gd2O3 enriched targets, performed at the Bern University Hospital cyclotron laboratory. On the basis of the obtained results, the production yield and purity were calculated to assess the optimal irradiation conditions. The results of several production tests are also presented.


Assuntos
Ciclotrons , Térbio , Humanos , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/química , Térbio/química , Tomografia Computadorizada de Emissão de Fóton Único/métodos
19.
Nat Protoc ; 17(4): 980-1003, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35246649

RESUMO

[68Ga]Ga-PSMA-11, a urea-based peptidomimetic, is a diagnostic radiopharmaceutical for positron emission tomography (PET) imaging that targets the prostate-specific membrane antigen (PSMA). The recent Food and Drug Administration approval of [68Ga]Ga-PSMA-11 for PET imaging of patients with prostate cancer, expected follow-up approval of companion radiotherapeutics (e.g., [177Lu]Lu-PSMA-617, [225Ac]Ac-PSMA-617) and large prostate cancer patient volumes requiring access are poised to create an unprecedented demand for [68Ga]Ga-PSMA-11 in nuclear medicine clinics around the world. Meeting this global demand is going to require a variety of synthesis methods compatible with 68Ga eluted from a generator or produced on a cyclotron. To address this urgent need in the PET radiochemistry community, herein we report detailed protocols for the synthesis of [68Ga]Ga-PSMA-11, (also known as HBED-CC, Glu-urea-Lys(Ahx)-HBED-CC and PSMA-HBED-CC) using both generator-eluted and cyclotron-produced 68Ga and contrast the pros and cons of each method. The radiosyntheses are automated and have been validated for human use at two sites (University of Michigan (UM), United States; Royal Prince Alfred Hospital (RPA), Australia) and used to produce [68Ga]Ga-PSMA-11 for patient use in good activity yields (single generator, 0.52 GBq (14 mCi); dual generators, 1.04-1.57 GBq (28-42 mCi); cyclotron method (single target), 1.47-1.89 GBq (40-51 mCi); cyclotron method (dual target), 3.63 GBq (98 mCi)) and high radiochemical purity (99%) (UM, n = 645; RPA, n > 600). Both methods are appropriate for clinical production but, in the long term, the method employing cyclotron-produced 68Ga is the most promising for meeting high patient volumes. Quality control testing (visual inspection, pH, radiochemical purity and identity, radionuclidic purity and identity, sterile filter integrity, bacterial endotoxin content, sterility, stability) confirmed doses are suitable for clinical use, and there is no difference in clinical prostate cancer PET imaging using [68Ga]Ga-PSMA-11 prepared using the two production methods.


Assuntos
Neoplasias da Próstata , Compostos Radiofarmacêuticos , Ciclotrons , Ácido Edético , Radioisótopos de Gálio/química , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/diagnóstico por imagem , Ureia
20.
Med Phys ; 49(4): 2709-2724, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35134261

RESUMO

PURPOSE: 64 Cu and 67 Cu radioisotopes have nuclear characteristics suitable for nuclear medicine applications. The production of 64 Cu is already well established. However, the production of 67 Cu in quantities suitable to conduct clinical trials is more challenging as it leads to the coproduction of other Cu isotopes, in particular 64 Cu. The aim of this study is to investigate the possibility of using a CuCl2 solution with a mixture of 67/64 Cu radioisotopes for therapeutic purposes, providing an alternative solution for the cyclotron production problem. METHODS: Copper radioisotopes activities were calculated by considering proton beam irradiation of the following targets: (i) 70 Zn in the energy range 70-45 MeV; (ii) 68 Zn in the energy range 70-35 MeV; (iii) a combination of 70 Zn (70-55 MeV) and 68 Zn (55-35 MeV). The contribution of each copper radioisotope to the human-absorbed dose was estimated with OLINDA/EXM software using the biokinetic model for CuCl2 published by ICRP 53. The total absorbed dose generated by the 67/64 CuCl2 mixture, obtained through different production routes, was calculated at different times after the end of the bombardment (EOB). A simple spherical model was used to simulate tumors of different sizes containing uniformly distributed 67/64 Cu mixture and to calculate the absorbed dose of self-irradiation. The biological damage produced by 67 Cu and 64 Cu was also evaluated through cellular dosimetry and cell surviving fraction assessment using the MIRDcell code, considering two prostate cancer cell lines with different radiosensitivity. RESULTS: The absorbed dose to healthy organs and the effective dose (ED) per unit of administered activity of 67 CuCl2 are higher than those of 64 CuCl2 . Absorbed dose values per unit of administered activity of 67/64 CuCl2 mixture increase with time after the EOB because the amount of 67 Cu in the mixture increases. Survival data showed that the biological damage caused per each decay of 67 Cu is greater than that of 64 Cu, assuming that radionuclides remain accumulated in the cell cytoplasm. Sphere model calculations demonstrated that 64 Cu administered activity must be about five times higher than that of 67 Cu to obtain the same absorbed dose for tumor mass between 0.01 and 10 g and about 10 times higher for very small spheres. Consequently, the 64 CuCl2 -absorbed dose to healthy organs will reach higher values than those of 67 CuCl2 . The supplemental activity of the 67/64 CuCl2 mixture, required to get the same tumor-absorbed dose produced by 67 CuCl2 , triggers a dose increment (DI) in healthy organs. The waiting time post-EOB necessary to keep this DI below 10% (t10% ) depends on the irradiation methods employed for the production of the 67/64 CuCl2 mixture. CONCLUSIONS: A mixture of cyclotron produced 67/64 Cu radioisotopes proved to be an alternative solution for the therapeutic use of CuCl2 with minimal DI to healthy organs compared with pure 67 Cu. Irradiation of a 70 Zn+68 Zn target in the 70-35 MeV proton energy range for 185 h appears to be the best option from among all the production routes investigated, as it gives the maximum amount of activity, the shortest t10% (10 h), and less than 1% of 61 Cu and 60 Cu impurities.


Assuntos
Ciclotrons , Neoplasias , Radioisótopos de Cobre , Estudos de Viabilidade , Humanos , Masculino , Neoplasias/tratamento farmacológico , Prótons , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos
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