Assessment of Area Radiation Dose for the National Cyclotron and PET Centre at Chulabhorn Hospital in Thailand.

The National Cyclotron and PET Centre at Chulabhorn Hospital offers nuclear medicine diagnostic services using state-of-the-art digital PET/CT and PET/MRI machines as well as other related devices. Additionally, the center plays a vital role by having a cyclotron to produce radiopharmaceuticals, which are used both in-house and in other hospitals throughout the country. Despite the center's strict adherence to international standards regarding the use of radioactive substances in patients, there remains a potential risk of radiation exposure for operators, workers, and the public due to radioactive contamination and emissions from unsealed sources. Hence, it is imperative to assess and continuously monitor radiation levels in the work area to ensure the utmost level of safety for personnel. Methods: This study used optically stimulated luminescence dosimeters to measure radiation levels in 17 areas, consisting of 9 controlled and 8 supervised areas. Over a 3-mo period, the average monthly radiation dose was recorded for each location. Results: The PET/CT room registered the highest radiation dose within the controlled area, with a monthly average of 1.81 ± 0.29 mSv, equivalent to an annual dose of 21.72 mSv. This higher dose can be attributed to the significant number of patients served in this room. In supervised areas, the nursing counter located between the examination room and the patient waiting area exhibited the highest radiation exposure. The average monthly dose measured at this location was 0.085 ± 0.019 mSv, resulting in an annual dose of 1.015 mSv. Conclusion: The evaluation of radiation dose in controlled and supervised areas indicated that the overall radiation level remains within the prescribed limits. However, the slight excess that was observed at the nursing counter indicates the need for improvement to ensure compliance with the as-low-as-reasonably-achievable principle. Continuous monitoring of radiation levels should be conducted annually to maintain safety standards and minimize the risk that workers and the general public will be exposed to radioactivity.

Monte Carlo modelling of cyclotron and radioisotope center (CYRIC) at Tohoku University: a radiation protection study.

Protection against ionizing radiations is important in laboratories with radioactive materials and high energy cyclotron beams. The Cyclotron and Radioisotope Center (CYRIC) located in Tohoku University in Miyagi prefecture, Japan and is a well-known nuclear science laboratory with cyclotron beams and substantial number of high activity radioactive materials. Considering this, it is important to perform complete radiation transport computations to ensure the safety of non-occupational and occupational workers. In the present work, we have developed a complete 3-dimensional model of the main cyclotron building and radiation labs using Monte Carlo method. We have found that the dispersed photons and neutrons inside and in the surrounding of the CYRIC building pose no significant risk to occupational and non-occupational workers. The present work and the developed models would be useful in the field of radiation protection.

High spatiotemporal resolution scintillation imaging of pulsed pencil beam scanning proton beams produced by a gantry-mounted synchrocyclotron.

BACKGROUND: A dosimeter with high spatial and temporal resolution would be of significant interest for pencil beam scanning (PBS) proton beams' characterization, especially when facing small fields and beams with high temporal dynamics. Optical imaging of scintillators has potential in providing sub-millimeter spatial resolution with pulse-by-pulse basis temporal resolution when the imaging system is capable of operating in synchrony with the beam-producing accelerator. PURPOSE: We demonstrate the feasibility of imaging PBS proton beams as they pass through a plastic scintillator detector to simultaneously obtain multiple beam parameters, including proton range, pencil beam's widths at different depths, spot's size, and spot's position on a pulse-by-pulse basis with sub-millimeter resolution. MATERIALS AND METHODS: A PBS synchrocyclotron was used for proton irradiation. A BC-408 plastic scintillator block with 30 × 30 × 5 cm3 size, and another block with 30 × 30 × 0.5 cm3 size, positioned in an optically sealed housing, were used sequentially to measure the proton range, and spot size/location, respectively. A high-speed complementary metal-oxide-semiconductor (CMOS) camera system synchronized with the accelerator's pulses through a gating module was used for imaging. Scintillation images, captured with the camera directly facing the 5-cm-thick scintillator, were corrected for background (BG), and ionization quenching of the scintillator to obtain the proton range. Spots' position and size were obtained from scintillation images of the 0.5-cm-thick scintillator when a 45° mirror was used to reflect the scintillation light toward the camera. RESULTS: Scintillation images with 0.16 mm/pixel resolution corresponding to all proton pulses were captured. Pulse-by-pulse analysis showed that variations of the range, spots' position, and size were within ± 0.2% standard deviation of their average values. The absolute ranges were within ± 1 mm of their expected values. The average spot-positions were mostly within ± 0.8 mm and spots' sigma agreed within 0.2 mm of the expected values. CONCLUSION: Scintillation-imaging PBS beams with high-spatiotemporal resolution is feasible and may help in efficient and cost-effective acceptance testing and commissioning of existing and even emerging technologies such as FLASH, grid, mini-beams, and so forth.

Commissioning of the first hospital-based PET radiopharmaceutical cyclotron in Greece: personnel dose assessment.

The role of18F-fluoro-deoxy-glucose in positron emission tomography (PET) imaging is well established in diagnosis and management of cancer patients. Installations of on-site self-shielded mini cyclotrons are increasing. The Dose on Demand Biomarker Generator BG-75 was installed at Metaxa Cancer Hospital, Greece, in May 2021 and is the first hospital-based PET radiopharmaceutical cyclotron in the country. Personnel expected external exposure was established during commissioning; internal exposure is not expected. Personnel dose was estimated with two methods: survey meter measurements in various locations combined with the time spent in each location, and direct measurement using electronic personal dosemeters. Gamma and neutron radiation readings outside the cyclotron vault were at background levels. Inside the cyclotron vault, the highest recorded radiation readings by the target were 18µSv h-1for both gammas and neutrons with cyclotron in operational mode; at one meter, the values were 5µSv h-1and 4µSv h-1, respectively. The annual expected whole body dose per cyclotron operator is 0.6 mSv, and the respective extremity dose 16 mSv. The annual expected whole body and extremity dose for the radiochemist is 0.3 mSv and 25 mSv, respectively. The respective annual dose estimates for the medical physicists are < 1 mSv. The expected personnel doses are well below the regulatory limits and local as low as reasonably achievable (ALARA) levels. With experience and a robust ALARA program, personnel exposure could be further reduced.

Two-Dimensional Fourier Transform Ion Cyclotron Resonance Mass Spectrometry of N-Linked Glycopeptides.

Glycosylation is a common modification across living organisms and plays a central role in understanding biological systems and disease. Our ability to probe the gylcome has grown exponentially in the past several decades. However, further improvements to the analytical toolbox available to researchers would allow for increased capabilities to probe structure and function of biological systems and to improve disease treatment. This article applies the developing technique of two-dimensional Fourier transform ion cyclotron resonance mass spectrometry to a glycoproteomic workflow for the standard glycoproteins coral tree lectin (CTL) and bovine ribonuclease B (BRB) to demonstrate its feasibility as a tool for glycoproteomic workflows. 2D infrared multiphoton dissociation and electron capture dissociation spectra of CTL reveal comparable structural information to their 1D counterparts, confirming the site of glycosylation and monosaccharide composition of the glycan. Spectra collected in 2D of BRB reveal correlation lines of fragment ion scans and vertical precursor ion scans for data collected using infrared multiphoton dissociation and diagonal cleavage lines for data collected by electron capture dissociation. The use of similar techniques for glycoproteomic analysis may prove valuable in instances where chromatographic separation is undesirable or quadrupole isolation is insufficient.

Electron plasma diagnostics in ELTRAP by electron cyclotron resonance heating method.

Electron cyclotron resonance heating method of Particle-in-Cell code was used to analyze heating phenomena, axial kinetic energy, and self-consistent electric field of confined electron plasma in ELTRAP device by hydrogen and helium background gases. The electromagnetic simulations were performed at a constant power of 3.8 V for different RF drives (0.5 GHz- 8 GHz), as well as for 1 GHz constant frequency at these varying amplitudes (1 V-3.8 V). The impacts of axial and radial temperatures were found maximum at 1.8 V and 5 GHz as compared to other amplitudes and frequencies for both background gases. These effects are higher at varying radio frequencies due to more ionization and secondary electrons production and maximum recorded radial temperature for hydrogen background gas was 170.41 eV. The axial kinetic energy impacts were found more effective in the outer radial part (between 0.03 and 0.04 meters) of the ELTRAP device due to applied VRF through C8 electrode. The self-consistent electric field was found higher for helium background gas at 5 GHz RF than other amplitudes and radio frequencies. The excitation and ionization rates were found to be higher along the radial direction (r-axis) than the axial direction (z-axis) in helium background gas as compared to hydrogen background gas. The current studies are advantageous for nuclear physics applications, beam physics, microelectronics, coherent radiation devices and also in magnetrons.

Cyclotron and linear accelerator generated scanning proton beams for lung cancer SBRT: Interplay effects and mitigations.

BACKGROUND: Pencil beam scanning (PBS) proton therapy for moving targets is known to be impacted by interplay effects between the scanning beam and organ motion. While respiratory motion in the thoracic region is the major cause for organ motion, interplay effects depend on the delivery characteristics of proton accelerators. PURPOSE: To evaluate the impact of different types of PBS proton accelerators and spot sizes on interplay effects, mitigations, and plan quality for Stereotactic Body Radiation Therapy (SBRT) treatment of non-small cell lung cancer (NSCLC). METHODS: Twenty NSCLC patients treated with photon SBRT were selected to represent varying tumor volumes and respiratory motion amplitudes (median: 0.6 cm with abdominal compression) for this retrospective study. For each patient, plans were created using: (1) cyclotron-generated proton beams (CPB) with spot sizes of σ = 2.7-7.0 mm; (2) linear accelerator proton beams (LPB) (σ = 2.9-5.5 mm); and (3) linear accelerator proton minibeams (LPMB) (σ = 0.9-3.9 mm). The energy switching time is one second for CPB, and 0.005 s for LPMB and LPB. Plans were robustly optimized on the gross tumor volume (GTV) using each individual phase of four-dimensional computed tomography (4DCT) scans. Initially, single-field optimization (SFO) plans were evaluated; if the plan quality did not meet the dosimetric requirement, multi-field optimization (MFO) was used. MFO plans were created for all patients for comparisons. For each patient, all plans were normalized to have the same dose received by 99% of the GTV. Interplay effects were evaluated by computing the dose on 10 breathing phases, based on the spot distribution. Volumetric repainting (VR) was performed 2-6 times for each plan. We compared volume receiving 100% of the prescribed dose (V100%RX) of the GTV, and normal lung V20Gy. RESULTS: Twelve of 20 plans can be optimized sufficiently with SFO. SFO plans were less sensitive to the interplay effect compared to MFO plans in terms of target coverage for both LPB and LPMB. The following comparisons showed results utilizing the MFO technique. In the interplay evaluation without repainting, the mean V100%RX of the GTV were 99.42 ± 0.6%, 97.52 ± 3.9%, and 94.49 ± 7.3% for CPB, LPB, and LPMB plans, respectively. Following VR (2 × for CPB; 3 × for LPB; 5 × for LPMB), V100%RX of the GTV were improved (on average) by 0.13%, 1.84%, and 4.63%, respectively, achieving the acceptance criteria of V100%RX > 95%. Because of fast energy switch in linear accelerator proton machines, the delivery time for VR plans was the lowest for LPB plans, while delivery time for LPMB was on average 1 min longer than CPB plans. The advantage of small spot machines was better sparing in normal lung V20Gy, even when VR was applied. CONCLUSION: In the absence of repainting, proton machines with large spot sizes generated more robust plans against interplay effects. The number of VR increased with decreasing spot sizes to achieve the acceptance criteria. VR improved the plan robustness against interplay effects for modalities with small spot sizes and fast energy changes, preserving the low dose sparing aspect of the LPMB, even when motion is included.

Utilising Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to track the oxidation of lignin by an alkaliphilic laccase.

Lignin is a complex heteroaromatic polymer which is one of the most abundant and diverse biopolymers on the planet. It comprises approximately one third of all woody plant matter, making it an attractive candidate as an alternative, renewable feedstock to petrochemicals to produce fine chemicals. However, the inherent complexity of lignin makes it difficult to analyse and characterise using common analytical techniques, proving a hindrance to the utilisation of lignin as a green chemical feedstock. Herein we outline the tracking of lignin degradation by an alkaliphilic laccase in a semi-quantitative manner using a combined chemical analysis approach using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to characterise shifts in chemical diversity and relative abundance of ions, and NMR to highlight changes in the structure of lignin. Specifically, an alkaliphilic laccase was used to degrade an industrially relevant lignin, with compounds such as syringaresinol being almost wholly removed (95%) after 24 hours of treatment. Structural analyses reinforced these findings, indicating a >50% loss of NMR signal relating to ß-ß linkages, of which syringaresinol is representative. Ultimately, this work underlines a combined analytical approach that can be used to gain a broader semi-quantitative understanding of the enzymatic activity of laccases within a complex, non-model mixture.

Improved purification of cyclotron [68Ga]GaCl3 for the production of 68Ga radiopharmaceuticals.

INTRODUCTION: Increased demand for NetSpot and Illuccix as requirement to receive the respective Lutathera and Pluvicto radiotherapies, and monitor subsequent response to treatment, have reinforced the need to develop alternative ways of producing gallium-68 (68Ga). Building on our efforts to produce 68Ga in a liquid target on a GE PETtrace, the goal of this work is to modify the current GE Gallium Chloride cassette using the FASTLab 2 synthesis module to produce [68Ga]GaCl3 equivalent to a 1.85 GBq generator and demonstrate compatibility with FDA-approved kits for production of 68Ga-labeled radiopharmaceuticals. METHODS: 68Ga was produced in a liquid target via the 68Zn(p,n)68Ga reaction. 68Ga was loaded onto various sizes of ZR resins (ZR Load, 0.3 mL, 1 mL, or 2 mL). The loading efficiency was determined using a dose calibrator. After washing with HNO3, 1.75 M HCl was used to elute the ZR Load resin through various sizes of a second ZR resin (ZR CG, 0 mL, 2 mL, 4 mL). Using 0.5 mL fractions, the elution profile was determined. Compatibility of the [68Ga]GaCl3 with NetSpot and Illuccix kits was investigated. Radiochemical purity (RCP) and 4 h stability were determined using radioTLC and radioHPLC. Using a modified [68Ga]GaCl3 cassette and new FASTLab program, 6 validation preparations were conducted using NetSpot and Illuccix kits for which RCP, stability, sterility and suitability were determined. Dual irradiation of 2 liquid targets was also performed, which was used to simultaneously prepare 1 NetSpot and 2 Illuccix kits by diluting the required activity with 0.1 M HCl. RESULTS: The commercially available GE Cassette gave low RCP using commercial FDA kits. To optimize this, the loading efficiency onto ZR Load and the ratio of ZR resin used to load the initial activity and subsequent elution were explored. When using a 2:4 ratio of ZR Load to ZR CG, 97.89 % RCP was observed when a 3.8 mL [68Ga]GaCl3 solution was used. For Dotatate validation, 0.55 mL of buffer was added to 4.2 mL of [68Ga]GaCl3 which gave 1.35 GBq of formulated product. For Illuccix validation, [68Ga]GaCl3 was added to 2.5 mL of buffer which gave 1.52 GBq of [68Ga]Ga-PSMA-11. Formulated products passed package insert quality control (QC) requirements. When dual target irradiations were performed, 2.84 GBq was delivered to an external vial and used to label 1 NetSpot and 2 Illuccix kits simultaneously, and each kit also met or exceeded established QC criteria. CONCLUSION: Methods are reported for using cyclotron-produced 68Ga from a liquid target in conjunction with FDA-approved NetSpot and Illucix kits. By employing a 2 mL ZR Load resin with a 4 mL ZR CG resin, adequate resolution between residual 68Zn and desired 68Ga was achieved. By modifying the FASTLab procedure to retain the final 2.5 mL of eluate from the ZR CG resin, [68Ga]GaCl3 equivalent to a new 1.85 GBq generator was obtained. This was suitable for labeling NetSpot and Illucix kits, resulting in high incorporation of 68Ga (RCP >95 %), which has not previously been demonstrated. Delivering [68Ga]GaCl3 into an external vial and diluting with 0.1 M HCl makes it possible to prepare multiple kits simultaneously. These new procedures should facilitate use of cyclotron-produced [68Ga]GaCl3 for clinical production going.

Radiolabeling Diaminosarcophagine with Cyclotron-Produced Cobalt-55 and [55Co]Co-NT-Sarcage as a Proof of Concept in a Murine Xenograft Model.

Cobalt-sarcophagine complexes exhibit high kinetic inertness under various stringent conditions, but there is limited literature on radiolabeling and in vivo positron emission tomography (PET) imaging using no carrier added 55Co. To fill this gap, this study first investigates the radiolabeling of DiAmSar (DSar) with 55Co, followed by stability evaluation in human serum and EDTA, pharmacokinetics in mice, and a direct comparison with [55Co]CoCl2 to assess differences in pharmacokinetics. Furthermore, the radiolabeling process was successfully used to generate the NTSR1-targeted PET agent [55Co]Co-NT-Sarcage (a DSar-functionalized SR142948 derivative) and administered to HT29 tumor xenografted mice. The [55Co]Co-DSar complex can be formed at 37 °C with purity and stability suitable for preclinical in vivo radiopharmaceutical applications, and [55Co]Co-NT-Sarcage demonstrated prominent tumor uptake with a low background signal. In a direct comparison with [64Cu]Cu-NT-Sarcage, [55Co]Co-NT-Sarcage achieved a higher tumor-to-liver ratio but with overall similar biodistribution profile. These results demonstrate that Sar would be a promising chelator for constructing Co-based radiopharmaceuticals including 55Co for PET and 58mCo for therapeutic applications.

44Sc production from enriched 47TiO2 targets with a medical cyclotron.

44Sc is a ß+-emitter which has been extensively studied for nuclear medicine applications. Its promising decay characteristics [t1/2 = 3.97 h, E [Formula: see text] = 632 keV (94.3%), Eγ = 1157 keV (99.9%); 1499 keV (0.91%)] make it highly attractive for clinical PET imaging, offering an alternative to the widely used 68Ga [t1/2 = 67.7 min, E [Formula: see text] = 836 keV (87.7%)]. Notably, its nearly fourfold longer half-life opens avenues for applications with biomolecules having extended biological half-lives and enables the centralized distribution of 44Sc radiopharmaceuticals. An additional advantage of employing 44Sc as a diagnostic radioisotope lies in its counterpart, the ß--emitter 47Sc, which is currently under investigation for targeted radiotherapy. Together, they form an ideal theranostic pair, providing a comprehensive solution for both diagnostic imaging and therapeutic applications in nuclear medicine. At the Bern medical cyclotron, a study to optimize the production of scandium radioisotopes is currently ongoing. In this context, proton irradiation of titanium targets has been investigated, exploiting the reactions 47Ti(p,α)44Sc and 50Ti(p,α)47Sc. This approach enables the production of Sc radioisotopes within a single PET medical cyclotron facility, employing identical chemical procedures for target preparation and post-irradiation processing. In this paper, we report on cross-section measurements of the 47Ti(p,α)44Sc nuclear reaction using 95.7% enriched 47TiO2 targets. On the basis of the obtained results, the production yield and purity were calculated to assess the optimal irradiation conditions. Production tests were performed to confirm these findings.

Radioprotection in the production of 18F-FDG at Brazilian cyclotron facilities: A comparative study based on dosimetry.

Since the end of the Brazilian state monopoly in 2006, allowing private enterprises to act in producing and commercializing short half-life radiopharmaceuticals, the country observed a growth in the laboratories that use 18F-FDG to PET/CT exams. Considering the radiological protection and safety techniques applied to radioisotope-producing facilities or units, this study assembled the current situation of radiological protection showing the received doses of the professionals of four facilities with cyclotrons for 18F-FDG located in south and southeast Brazil in the years 2020 and 2021. The dose values observed are below the dose limits established by national and international regulatory entities but can still be optimized considering differences between the production units.

Decommissioning of a Medical Cyclotron Vault: The Case Study of the National Cancer Institute of Milano.

ABSTRACT: In the widespread use of medical cyclotrons for isotope production, radiological and economic consequences related to the decommissioning of particle accelerators are often neglected. However, decommissioning regulation and its related procedures always demand efforts and costs that can unexpectedly impact on budgets. The magnitude of this impact depends strongly on the residual radioactivity of the accelerator and of the vault, and more specifically on the kind and activity concentration of residual radionuclides. This work reports and discusses a case study that analyzes in detail the characterization activities needed for optimized management of the decommissioning of a medical cyclotron vault. In particular, this paper presents the activities carried out for assessing the activity concentrations and for guiding the disposal of the cyclotron vault of the Italian National Cancer Institute of Milano (INT). An unshielded 17 MeV cyclotron vault was characterized by high resolution gamma-ray spectrometry both in-situ and in-laboratory on extracted samples. Monte Carlo simulations were also carried out to assess the overall distribution of activation in the vault. After a few months from the final shutdown of the accelerator, activity concentrations in the concrete walls due to neutron activation exceeded the clearance levels in many regions, especially close to the cyclotron target. Due to the relatively long half-lives of some radionuclides, a time interval of about 20 y after the end of bombardment is necessary for achieving clearance in some critical positions. Far from the target or in positions shielded by the cyclotron, activation levels were below the clearance level. The comparison between Monte Carlo simulations and experimental results shows a good agreement. The in-situ measurements, simpler and economically advantageous, cannot completely replace the destructive measurements, but they may limit the number of required samples and consequently the decommissioning costs. The methodology described and the results obtained demonstrated that it is possible to obtain accurate estimations of activity concentrations with cheap and quick in-situ measurements if the concentration profile in-depth inside the wall is well known. This profile can be obtained either experimentally or numerically through suitably validated Monte Carlo simulations.

Performance evaluation of Gallium-68 radiopharmaceuticals production using liquid target PETtrace 800 cyclotron.

Due to increased demand, cyclotron has an expanding role in producing Gallium-68 (68Ga) radiopharmaceuticals using solid and liquid targets. Though the liquid target produces lower end-of-bombardment activity compared to the solid target, our study presents the performance of 68Ga radiopharmaceuticals production using the liquid target by evaluating the end-of-bombardment activity and the end-of-purification activity of [68Ga]GaCl3. We also present the effect of increasing irradiation time, which significantly improves the end-of-synthesis yield. From the result obtained, the end-of-bombardment activity produced was 4.48 GBq, and the [68Ga]GaCl3 end-of-purification activity produced was 2.51 GBq with below-limit metallic impurities. Increasing the irradiation time showed a significant increase in the end-of-synthesis activity from 1.33 GBq to 1.95 GBq for [68Ga]Ga-PSMA-11 and from 1.13 GBq to 1.74 GBq for [68Ga]Ga-DOTA-TATE. Based on the improvements made, the liquid target production of 68Ga radiopharmaceuticals is feasible and reproducible to accommodate up to 5 patients per production. In addition, this work also discusses the issues encountered, together with the possible corrective and preventative measures.

Beam monitor chamber calibration of a synchro-cyclotron high dose rate per pulse pulsed scanned proton beam.

Objective. Ionization chambers, mostly used for beam calibration and for reference dosimetry, can show high recombination effects in pulsed high dose rate proton beams. The aims of this paper are: first, to characterize the linearity response of newly designed asymmetrical beam monitor chambers (ABMC) in a 100-226 MeV pulsed high dose rate per pulse scanned proton beam; and secondly, to calibrate the ABMC with a PPC05 (IBA Dosimetry) plane parallel ionization chamber and compare to calibration with a home-made Faraday cup (FC).Approach. The ABMC response linearity was evaluated with both the FC and a PTW 60019 microDiamond detector. Regarding ionometry-based ABMC calibration, recombination factors were evaluated theoretically, then numerically, and finally experimentally measured in water for a plane parallel ionization chamber PPC05 (IBA Dosimetry) throughkssaturation curves. Finally, ABMC calibration was also achieved with FC and compared to the ionometry method for 7 energies.Main results. Linearity measurements showed that recombination losses in the new ABMC design were well taken into account for the whole range of the machine dose rates. The two-voltage-method was not suitable for recombination correction, but Jaffé's plots analysis was needed, emphasizing the current IAEA TRS-398 reference protocol limitations. Concerning ABMC calibration, FC based absorbed dose estimation and PPC05-based absorbed dose estimation differ by less than 6.3% for the investigated energies.Significance.So far, no update on reference dosimetry protocols is available to estimate the absorbed dose in ionization chambers for clinical high dose rate per pulse pulsed scanned proton beams. This work proposes a validation of the new ABMC design, a method to take into account the recombination effect for ionometry-based ABMC calibration and a comparison with FC dose estimation in this type of proton beams.

Production of pharmaceutical grade [201Tl]Thallous chloride using 30 MeV cyclotron.

Multiple patient doses of [201Tl]TlCl has been produced using electrodeposited enriched 203Tl in 30 MeV cyclotron (Cyclone-30) with 28 MeV proton energy at 50 µA beam current for 8 h. Ion Exchange Column Chromatography (IECC) and liquid-liquid extraction has been employed for semi-automated radiochemical separation and purification of produced [201Tl]TlCl. The produced [201Tl]TlCl was used in coronary artery disease (CAD) patients.

Ultrahigh-Mass Resolution Mass Spectrometry Imaging with an Orbitrap Externally Coupled to a High-Performance Data Acquisition System.

Matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) is a powerful analytical tool that enables molecular sample analysis while simultaneously providing the spatial context of hundreds or even thousands of analytes. However, because of the lack of a separation step prior to ionization and the immense diversity of biomolecules, such as lipids, including numerous isobaric species, the coupling of ultrahigh mass resolution (UHR) with MSI presents one way in which this complexity can be resolved at the spectrum level. Until now, UHR MSI platforms have been restricted to Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometers. Here, we demonstrate the capabilities of an Orbitrap-based UHR MSI platform to reach over 1,000,000 mass resolution in a lipid mass range (600-950 Da). Externally coupling the Orbitrap Q Exactive HF with the high-performance data acquisition system FTMS Booster X2 provided access to the unreduced data in the form of full-profile absorption-mode FT mass spectra. In addition, it allowed us to increase the time-domain transient length from 0.5 to 10 s, providing improvement in the mass resolution, signal-to-noise ratio, and mass accuracy. The resulting UHR performance generates high-quality MALDI MSI images and simplifies the identification of lipids. Collectively, these improvements resulted in a 1.5-fold increase in annotations, demonstrating the advantages of this UHR imaging platform for spatial lipidomics using MALDI-MSI.

Multi-institutional consensus on machine QA for isochronous cyclotron-based systems delivering ultra-high dose rate (FLASH) pencil beam scanning proton therapy in transmission mode.

BACKGROUND: The first clinical trials to assess the feasibility of FLASH radiotherapy in humans have started (FAST-01, FAST-02) and more trials are foreseen. To increase comparability between trials it is important to assure treatment quality and therefore establish a standard for machine quality assurance (QA). Currently, the AAPM TG-224 report is considered as the standard on machine QA for proton therapy, however, it was not intended to be used for ultra-high dose rate (UHDR) proton beams, which have gained interest due to the observation of the FLASH effect. PURPOSE: The aim of this study is to find consensus on practical guidelines on machine QA for UHDR proton beams in transmission mode in terms of which QA is required, how they should be done, which detectors are suitable for UHDR machine QA, and what tolerance limits should be applied. METHODS: A risk assessment to determine the gaps in the current standard for machine QA was performed by an international group of medical physicists. Based on that, practical guidelines on how to perform machine QA for UHDR proton beams were proposed. RESULTS: The risk assessment clearly identified the need for additional guidance on temporal dosimetry, addressing dose rate (constancy), dose spillage, and scanning speed. In addition, several minor changes from AAPM TG-224 were identified; define required dose rate levels, the use of clinically relevant dose levels, and the use of adapted beam settings to minimize activation of detector and phantom materials or to avoid saturation effects of specific detectors. The final report was created based on discussions and consensus. CONCLUSIONS: Consensus was reached on what QA is required for UHDR scanning proton beams in transmission mode for isochronous cyclotron-based systems and how they should be performed. However, the group discussions also showed that there is a lack of high temporal resolution detectors and sufficient QA data to set appropriate limits for some of the proposed QA procedures.

Top-Down Proteoform Analysis by 2D MS with Quadrupolar Detection.

Two-dimensional mass spectrometry (2D MS) is a multiplexed tandem mass spectrometry method that does not rely on ion isolation to correlate the precursor and fragment ions. On a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS), 2D MS instead uses the modulation of precursor ion radii inside the ICR cell before fragmentation and yields 2D mass spectra that show the fragmentation patterns of all the analytes. In this study, we perform 2D MS for the first time with quadrupolar detection in a dynamically harmonized ICR cell. We discuss the advantages of quadrupolar detection in 2D MS and how we adapted existing data processing techniques for accurate frequency-to-mass conversion. We apply 2D MS with quadrupolar detection to the top-down analysis of covalently labeled ubiquitin with ECD fragmentation, and we develop a workflow for label-free relative quantification of biomolecule isoforms in 2D MS.

Modernization of safety environment for a dedicated beamline for proton ocular therapy.

BACKGROUND: Proton therapy is an effective treatment for ocular melanoma, and other tumors of the eye. The fixed horizontal beamline dedicated to ocular treatments at Massachusetts General Hospital was originally commissioned in 2002, with much of the equipment, safety features, and practices dating back to an earlier implementation at Harvard Cyclotron in the 1970s. PURPOSE: To describe the experience of reevaluation and enhancement of the safety environment for one of the longest continuously operating proton therapy programs. METHODS: Several enhancements in quality control had been introduced throughout the years of operation, as described in this manuscript, to better align the practice with the evolving standards of proton therapy and the demands of a modern hospital. We spotlight the design and results of the failure mode and effect analysis (FMEA), and subsequent actions introduced to mitigate the modes associated with elevated risk. The findings of the FMEA informed the specifications for the new software application, which facilitated the improved management of the treatment workflow and the image-guidance aspects of ocular treatments. RESULTS: Eleven failure modes identified as having the highest risk are described. Six of these were mitigated with the clinical roll-out of a new application for image-guided radiation therapy (IGRT). Others were addressed through task automation, the broader introduction of checklists, and enhancements in pre-treatment staff-led time-out. CONCLUSIONS: Throughout the task of modernizing the safety system of our dedicated ocular beamline, FMEA proved to be an effective instrument in soliciting inputs from the staff about safety and workflow concerns, helping to identify steps associated with elevated failure risks. Risks were reduced with the clinical introduction of a new IGRT application, which integrates quality management tools widely recognized for their role in risk mitigation: automation of the data transfer and workflow steps, and with the introduction of checklists and redundancy cross-checks.