Development of 225Ac/213Bi generator based on α-ZrP-PAN composite for targeted alpha therapy.

BACKGROUND: Radioligand therapy using alpha emitters has gained more and more prominence in the last decade. Despite continued efforts to identify new appropriate radionuclides, the combination of 225Ac/213Bi remains among the most promising. Bismuth-213 has been employed in clinical trials in combination with appropriate vectors to treat patients with various forms of cancer, such as leukaemia, bladder cancer, neuroendocrine tumours, melanomas, gliomas, or lymphomas. However, the half-life of 213Bi (T½ = 46 min) implies that its availability for clinical use is limited to hospitals possessing a 225Ac/213Bi radionuclide generator, which is still predominantly scarce. We investigated a new Ac/Bi generator system based on using the composite sorbent α-ZrP-PAN (zirconium(IV) phosphate as active component and polyacrylonitrile as matrix). The developed 225Ac/213Bi generator was subjected to long-term testing after its development. The elution profile was determined and the elution yield, the contamination of the eluate with the parent 225Ac and the contamination of the eluate with the column material were monitored over time. RESULTS: The high activity (75 MBq of parent 225Ac) generator with a length of 75 mm and a diameter of 4 mm containing the composite sorbent α-ZrP-PAN with a particle size of 0.8 to 1.0 mm as the stationary phase, eluted with a mixture of 10 mM DTPA in 5 mM nitric acid, provided 213Bi with yields ranging from 77 % to 96 % in 2.8 mL of eluate, with parent 225Ac contamination in the order of 10-3 %, up to twenty days of use. CONCLUSION: All the results of the monitored parameters indicate that the composite sorbent α-ZrP-PAN based separation system for the elution of 213Bi is a very promising and functional solution.

Microfluidic Preparation of 89Zr-Radiolabelled Proteins by Flow Photochemistry.

89Zr-radiolabelled proteins functionalised with desferrioxamine B are a cornerstone of diagnostic positron emission tomography. In the clinical setting, 89Zr-labelled proteins are produced manually. Here, we explore the potential of using a microfluidic photochemical flow reactor to prepare 89Zr-radiolabelled proteins. The light-induced functionalisation and 89Zr-radiolabelling of human serum albumin ([89Zr]ZrDFO-PEG3-Et-azepin-HSA) was achieved by flow photochemistry with a decay-corrected radiochemical yield (RCY) of 31.2 ± 1.3% (n = 3) and radiochemical purity >90%. In comparison, a manual batch photoreactor synthesis produced the same radiotracer in a decay-corrected RCY of 59.6 ± 3.6% (n = 3) with an equivalent RCP > 90%. The results indicate that photoradiolabelling in flow is a feasible platform for the automated production of protein-based 89Zr-radiotracers, but further refinement of the apparatus and optimisation of the method are required before the flow process is competitive with manual reactions.

Potential for production of medical radionuclides with on-line isotope separation at the ISAC facility at TRIUMF and particular discussion of the examples of 165Er and 155Tb.

Production of medical radionuclides with ISOL facilities is a unique production method that may provide access to preclinical quantities of some rare and potent radionuclides for nuclear medicine. Particularly attention over the past years was focused on several promising candidates for Targeted Radionuclides Therapy (TRT). With this review, we provide some perspectives of using the TRIUMF ISOL facility (ISAC) to produce medical radionuclides for TRT application and highlight our current effort to collect of 165Er and 155Tb for Auger Therapy and SPECT imaging, respectively.

Preliminary dosimetric analysis of DOTA-folate radiopharmaceutical radiolabelled with 47Sc produced through natV(p,x)47Sc cyclotron irradiation.

47Sc is one of the most promising theranostic radionuclides, thanks to its low energy γ-ray emission (159 keV), suitable for single photon emission computed tomography imaging and its intense ß - emission, useful for tumour treatment. Despite promising preclinical results, the translation of 47Sc-therapeutic agents to the clinic is hampered by its limited availability. Among different 47Sc-production routes currently being investigated, the natV(p,x)47Sc reaction has proved to be of particular interest, thanks to the low-cost and easy availability on the market of natV material and the diffusion of medium energy proton cyclotrons. However, the cross section of this specific nuclear reaction is quite low and small amounts of Sc-contaminants are co-produced at energies E P ≤ 45 MeV, namely 48Sc and 46Sc. The main concern with these Sc-contaminants is their contribution to the patient absorbed dose. For such a reason, the absorbed dose contributions to healthy organs and the effective dose contributions by the three radioisotopes, 48Sc, 47Sc and 46Sc, were evaluated using DOTA-folate conjugate (cm10) as an example of radiopharmaceutical product. Considering as acceptable the limits of 99% for the radionuclidic purity and 10% for the contribution of radioactive Sc-contaminants to the total effective dose after 47Sc-cm10 injection, it was obtained that proton beam energies below 35 MeV must be used to produce 47Sc through irradiation of a natV target.

Cyclotron Production and Separation of Scandium Radionuclides from Natural Titanium Metal and Titanium Dioxide Targets.

Theranostic strategies involve select radionuclides that allow diagnostic imaging and tailored radionuclide therapy in the same patient. An example of a Food and Drug Administration-approved theranostic pair is the 68Ga- and 177Lu-labeled DOTATATE peptides, which are used to image neuroendocrine tumors, predict treatment response, and treat disease. However, when using radionuclides of 2 different elements, differences in the pharmacokinetic and pharmacodynamic profile of the agent can occur. Theranostic agents that incorporate the matched-pair radionuclides of scandium-43Sc/47Sc or 44Sc/47Sc-would guarantee identical chemistries and pharmacologic profiles. The aim of this study was to investigate production of 43,44,47Sc via proton-induced nuclear reactions on titanium nuclei using a 24-MeV cyclotron. Methods: Aluminum, niobium, and tantalum target holders were used with titanium foils and pressed TiO2 to produce scandium radionuclides with proton energies of up to 24 MeV. Irradiated targets were digested using NH4HF2 and HCl in a closed perfluoroalkoxy alkane vessel in 90 min. Scandium radionuclides were purified via ion-exchange chromatography using branched N,N,N',N'-tetra-2-ethylhexyldiglycolamide. The titanium target material was recovered via alkali precipitation with ammonia solution. Results: Titanium foil and TiO2 were digested with an average efficiency of 98% ± 3% and 95% ± 1%, respectively. The typical digestion time was 45 min for titanium foil and 75 min for TiO2 The average scandium recovery was 94% ± 3%, and the average titanium recoveries from digested titanium foil and TiO2 after precipitation as TiO2 were 108% ± 8% and 104% ± 5% of initial mass, respectively. Conclusion: This work demonstrated a robust method for the cyclotron production of scandium radionuclides that could be used with natural or enriched TiO2 target material.

Reactor produced [64Cu]CuCl2 as a PET radiopharmaceutical for cancer imaging: from radiochemistry laboratory to nuclear medicine clinic.

OBJECTIVE: Copper-64 is a useful theranostic radioisotope that is attracting renewed interest from the nuclear medicine community in the recent times. This study aims to demonstrate the utility of research reactors to produce clinical-grade 64Cu via 63Cu(n,γ)64Cu reaction and use it in the form of [64Cu]CuCl2 as a radiopharmaceutical for PET imaging of cancer in human patients. METHODS: Copper-64 was produced by irradiation of natural CuO target in a medium flux research reactor. The irradiated target was radiochemically processed and detailed quality control analyses were carried out. Sub-acute toxicity studies were carried out with different doses of Cu in Wistar rats. The biological efficacy of the radiopharmaceutical was established in preclinical setting by biodistribution studies in melanoma tumor bearing mice. After getting regulatory approvals, [64Cu]CuCl2 formulation was clinically used for PET imaging of prostate cancer and glioblastoma patients. RESULTS: Large-scale (~ 30 GBq) production of 64Cu could be achieved in a typical batch and it was adequate for formulation of clinical doses for multiple patients. The radiopharmaceutical met all the purity requirements for administration in human subjects. Studies carried out in animal model showed that the toxicity due to "cold" Cu in clinical dose of [64Cu]CuCl2 for PET scans would be negligible. Clinical PET scans showed satisfactory uptake of the radiopharmaceutical in the primary cancer and its metastatic sites. CONCLUSIONS: To the best of our knowledge, this is the first study on use of reactor produced [64Cu]CuCl2 for PET imaging of cancer in human patients. It is envisaged that this route of production of 64Cu would aid towards affordable availability of this radioisotope for widespread clinical use in countries with limited cyclotron facilities.

Optimization of the radiosynthesis of [68Ga]Ga-PSMA-11 using a Trasis MiniAiO synthesizer: do we need to heat and purify?

INTRODUTION:: [Ga]Ga-prostate specific membrane antigen (PSMA)-11 showed a clear gain in sensitivity for lesion detection in the biological recurrence of prostate cancer as compared to the standard [F]fluorocholine radiopharmaceutical. To meet the strong demand for [Ga]Ga-PSMA-11, we aimed to optimize an automated radiolabeling process by evaluating the influence of different key parameters on radiochemical purity and radiochemical yield. METHODS: The radiosynthesis of [Ga]Ga PSMA-11 was performed using a Trasis MiniAio synthesizer and a Ge/Ga GalliaPharm generator supplied by Eckert & Ziegler, Berlin, Germany. Optimized labeling parameters were evaluated by variation of sodium acetate concentrations and temperature of radiolabeling as well as the purification process. RESULTS: For each condition tested, radiochemical purity was higher than 99% in the final vial without batch failure, indicating a robust and fast radiosynthesis process. Radiosynthesis without the solid phase extraction purification process at room temperature in less than 5 min resulted in a radiolabeling efficiency of over 99% and remained stable at least 4 h without manual processing to limit operator radiation exposure. CONCLUSION: The procedure was completely automated and provided a high radiochemical yield. It can be performed several times a day, facilitating the clinical demand of this radiopharmaceutical.

Development of a fully automated low-pressure [11 C]CO carbonylation apparatus.

[11 C]carbon monoxide ([11 C]CO) is a versatile synthon for radiolabeling of drug-like molecules for imaging studies with positron emission tomography (PET). We here report the development of a novel, user-friendly, fully automated, and good manufacturing practice (GMP) compliant low-pressure synthesis module for 11 C-carbonylation reactions using [11 C]CO. In this synthesis module, [11 C]CO was reliably prepared from cyclotron-produced [11 C]carbon dioxide ([11 C]CO2 ) by reduction over heated molybdenum and delivered to the reaction vessel within 7 min after end of bombardment, with an overall radiochemical yield (RCY) of 71%. [11 C]AZ13198083, a histamine type-3 receptor ligand, was used as a model compound to assess the functionality of the radiochemistry module. At full batch production conditions (55 µA, 30 min), our newly developed low-pressure 11 C-carbonylation apparatus enabled us to prepare [11 C]AZ13198083 in an isolated radioactivity of 8540 ± 1400 MBq (n = 3). The radiochemical purity of each of the final formulated batches exceeded 99%, and all other quality control tests results conformed with specifications typically set for carbon-11 labeled radiopharmaceuticals. In conclusion, this novel radiochemistry system offers a convenient GMP compliant production drugs and radioligands for imaging studies in human subjects.

Automated synthesis of 68 Ga/177 Lu-PSMA on the Trasis miniAllinOne.

Prostate-specific membrane antigen (PSMA)-based radioligands for positron emission tomography (PET)/computed tomography (CT) studies represent the gold standard for detection of recurrent prostate cancer (PCa). [68 Ga]PSMA-HBED-CC is a PET radiotracer suitable for detection of PCa, and its clinical use has become widespread over the last few years. In this contribution, we detail our GMP-compliant production of [68 Ga]PSMA-HBED-CC using the Trasis miniAllinOne radiosynthesizer and report synthetic and clinical data for the first 100 productions of 2019. Additionally, we detail our efforts towards a GMP-compliant production of the radiotherapeutic [177 Lu]PSMA-I&T using the same synthesis module. PSMA-based radioligand therapy (RLT) offers a possible future treatment in cases of metastatic castration-resistant PCa, and GMP-compliant routine production methods are therefore called for. This report highlights how PSMA-based agents for theranostic purposes can be conveniently produced at a single radiochemistry Good Manufacturing Practice (GMP) site, thereby facilitating optimized detection and treatment of PCa.

Influential Factors in the Preparation of 68Ga-DOTATATE.

Acceptable and reproducible radiochemical purity (RP) for 68Ga-DOTATATE was difficult to obtain with the NETSPOT kit because the manufacturer instructions lacked details on the heater or needles used. Methods: The drug was prepared in an International Organization for Standardization (ISO) 5 environment. Multiple dry baths and needle types were used to investigate the effects of reaction temperature and metal contamination, respectively. Temperature curves were obtained with a calibrated thermocouple. The influence of the accuracy of the NETSPOT reagent volume and its effect on outcome were investigated. Results: The AccuBlock dry bath required recalibration for the ISO 5 environment; after calibration, the temperature was stable (only ±0.1°C from the set point). When we followed package insert recommendations (dry bath temperature set to 98°C, reaction time of 8 min), the reaction temperature was 90.6°C. When Becton Dickinson needles were used for reconstitution, 15 of 18 runs (83%) did not meet the RP specification. However, B. Braun Medical needles achieved satisfactory and stable RP. When the 68Ga generator was eluted with 5.0 mL of 0.1 M hydrochloric acid (HCl), only 3.8-3.9 mL of eluate reached the reaction vial; this volume did not impact labeling (final pH was 3.8). The labeling success rate increased markedly if the 68Ga eluate was passed through a conditioned silica gel cartridge or if no cartridge was used; then, RP was more than 99%. HCl contact with the septum of the labeling vial reduced RP. Conclusion: The needle type and the temperature setting of the dry bath have critical roles in 68Ga-DOTATATE preparation. The AccuBlock dry bath has excellent stability and accuracy and can be used for reliable preparation. By using a conditioned silica gel cartridge or by eliminating the cartridge altogether, the RP is reliably high and stable.

Taking cyclotron 68Ga production to the next level: Expeditious solid target production of 68Ga for preparation of radiotracers.

INTRODUCTION: Gallium-68 is an important radionuclide for positron emission tomography (PET) with steadily increasing applications of 68Ga-based radiopharmaceuticals for clinical use. Current 68Ga sources are primarily 68Ge/68Ga-generators, along with successful attempts of 68Ga production using a cyclotron. This study evaluated cyclotron 68Ga production and automated separation using expeditiously manufactured solid targets, demonstrates an order of magnitude improvement in yield compared to 68Ge/68Ga generators, and presents a convenient alternative to existing cyclotron production processes. A comparison of radiolabeling and preclinical PET imaging was performed with both cyclotron and generator produced 68Ga. METHODS: 100 mg enriched 68Zn (99.3% 68Zn, 0.48% 67Zn, 0.1% 66Zn) pellets pressed on silver discs were bombarded for 20-75 min using 12.5 MeV proton beam energies and 10-30 µA currents. 68Ga was separated using an automated TRASIS AllinOne synthesizer employing AG 50W-X8 and UTEVA resins. Post-separation recovery of the 68Zn by electrolysis yielded 76.7 ± 4.3%. Radionuclidic purity of cyclotron-produced 68Ga was investigated with gamma spectroscopy using a HPGe-detector. Radiolabeling was investigated using the macrocyclic chelator DOTA and the bombesin-derived peptide NOTA-BBN2. PET imaging was performed using [68Ga]Ga-NOTA-BBN2 in a PC3 xenograft model. RESULTS: 600 µA·min fresh and recycled quadruplet 68Zn target irradiations (n = 8) at 12.5 MeV and 30 µA yielded 13.9 ± 1.0 GBq 68Ga; 2200 µA·min irradiations (n = 3) yielded 37.5 ± 1.9 GBq 68Ga. HPGe analysis showed EOB 0.0074% and 0.0084% of total activity of 66Ga and 67Ga, respectively. Metal impurities were 0.06 ± 0.03 µg/GBq Zn, 0.13 ± 0.007 µg/GBq Fe, and 0.02 ± 0.01 µg/GBq Al for cyclotron 68Ga. Cyclotron and 68Ge/68Ga generator 68Ga respective DOTA and NOTA-BBN2 labeling incorporations were 99.4 ± 0.0% and 99.3 ± 0.2%, and 90.4 ± 1.5% and 93.0 ± 3.6% determined by radio-thin layer chromatography (radio-TLC). Preclinical PET imaging comparison between generator and cyclotron produced 68Ga showed identical radiotracer tumor uptake and biodistribution profiles in PC3 tumor bearing mice. CONCLUSIONS: Cyclotron 68Ga production provides highly scalable production with equivalent or superior quality 68Ga to a 68Ge/68Ga generator, while providing identical biodistribution and tumor uptake profiles. Our described targetry is simpler and more cost-effective than existing liquid and solid targetry, enabling a turnkey production system for multi-facility distribution of cyclotron produced 68Ga. The manufacturing simplicity described has potential applications for producing other radiometals such as 44Sc. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Our cost-effective method of solid target 68Ga production can enhance 68Ga production capabilities to meet the high demand for 68Ga-radiopharmaceuticals for research and clinical use.

Improved production of 76Br, 77Br and 80mBr via CoSe cyclotron targets and vertical dry distillation.

INTRODUCTION: The radioisotopes of bromine are uniquely suitable radiolabels for small molecule theranostic radiopharmaceuticals but are of limited availability due to production challenges. Significantly improved methods were developed for the production and radiochemical isolation of clinical quality 76Br, 77Br, and 80mBr. The radiochemical quality of the radiobromine produced using these methods was tested through the synthesis of a novel 77Br-labeled inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), a DNA damage response protein. METHODS: 76Br, 77Br, and 80mBr were produced in high radionuclidic purity via the proton irradiation of novel isotopically-enriched Co76Se, Co77Se, and Co80Se intermetallic targets, respectively. Radiobromine was isolated through thermal chromatographic distillation in a vertical furnace assembly. The 77Br-labeled PARP inhibitor was synthesized via copper-mediated aryl boronic ester radiobromination. RESULTS: Cyclotron production yields were 103 ±â€¯10 MBq∙µA-1∙h-1 for 76Br, 88 ±â€¯10 MBq∙µA-1∙h-1 for 80mBr at 16 MeV and 17 ±â€¯1 MBq∙µA-1∙h-1 for 77Br at 13 MeV. Radiobromide isolation yields were 76 ±â€¯11% in a small volume of aqueous solution. The synthesized 77Br-labeled PARP-1 inhibitor had a measured apparent molar activity up to 700 GBq/µmol at end of synthesis. CONCLUSIONS: A novel selenium alloy target enabled clinical-scale production of 76Br, 77Br, and 80mBr with high apparent molar activities, which was used to for the production of a new 77Br-labeled inhibitor of PARP-1. ADVANCES IN KNOWLEDGE: New methods for the cyclotron production and isolation of radiobromine improved the production capacity of 77Br by a factor of three and 76Br by a factor of six compared with previous methods. IMPLICATIONS FOR PATIENT CARE: Preclinical translational research of 77Br-based Auger electron radiotherapeutics, such as those targeting PARP-1, will require the production of GBq-scale 77Br, which necessitates next-generation, high-yielding, isotopically-enriched cyclotron targets, such as the novel intermetallic Co77Se.

Quality of radiochemical purity in multiple samples of various fractionated cold kits: Testing a cost & time effective technique.

OBJECTIVE: This study was aimed to assess technical aspects of fractionation of commonly used cold kits in Nuclear Medicine. MATERIALS AND METHODS: A total of 90 samples (30 samples each) of technetium-99m methylene diphosphonate (99mTc-MDP), 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 99mTc-dimercaptosuccinic acid (DMSA III) were taken on various days. The radiochemical purity was calculated of each fraction of these cold kits by using paper chromatography. RESULTS: The mean value of radiochemical purity of 99mTc -MDP, 99mTc -DTPA and 99mTc-DMSA(III) were calculated as ~ 95.12%, 91.43% and 95.68% and standard deviation (SD) were ~ 5.43, 8.36 and 3.88, respectively. Maximum time in which fractionation procedure completed i.e. time required for preparing the fraction or thawing was 10 minutes. All fractionated aliquots were between 1 and 15 days. Radiopharmaceutical bio-distribution was found to be appropriate during imaging in all samples. CONCLUSION: Fractionation of cold kits using standardised technique is a time and cost-effective method and does not deteriorate the quality of labelling in commonly used pharmaceuticals in our study. We have used fractionated aliquots up to 3 days of preparation in patients with clinically usable radiochemical purity. Deep frozen fractions can be used up to 15 days in our experience.

Improved procedures of Sc(OH)3 precipitation and UTEVA extraction for 44Sc separation.

BACKGROUND: 44Sc is becoming attractive as a PET radionuclide due to its decay characteristics. It can be produced from 44Ca present in natural calcium with 2.08% abundance. MATERIALS AND METHODS: The targets were mostly prepared from natural CaCO3 or metallic calcium in the form of pellets. After irradiation they were dissolved in 3 M hydrochloric acid and 44Sc was separated from excess of calcium by precipitation of scandium hydroxide using ammonia. Alternatively, targets were dissolved in 11 M hydrochloric acid and 44Sc was separated by extraction chromatography on UTEVA resin. As the next step, in both processes 44Sc was further purified on a cation exchange resin. Initially, the separation procedures were developed with 46Sc as a tracer. Gamma spectrometry with a high purity germanium detector was used to determine the separation efficiency. Finally, the CaCO3 pellet with 99.2% enrichment in 44Ca was activated with protons via 44Ca(p,n)44Sc nuclear reaction. RESULTS: Altogether twenty two irradiations and separations were performed. The working procedures were developed and the quality of separated 44Sc solution was confirmed by radiolabeling of DOTATATE. The chemical purity of the product was sufficient for preclinical experiments. At the end of around 1 hour proton beam irradiation of CaCO3 pellet with 99.2% enrichment in 44Ca the obtained radioactivity of 44Sc was more than 4.8 GBq. CONCLUSION: 44Sc can be produced inexpensively with adequate yields and radionuclidic purity via 44Ca(p,n)44Sc nuclear reaction in small cyclotrons. The recovery yield in both investigated separation methods was comparable and amounted above 90%. The obtained 44Sc was pure in terms of radionuclide and chemical purity, as shown by the results of peptide radiolabeling.

Industrial separation of oxygen isotopes by oxygen distillation.

18 O-labeled water (Water-18 O) is a widely used starting material of 18 F-labeled diagnostic agents in positron emission tomography (PET). Conventionally, Water-18 O has been separated from other stable oxygen isotope species (16 O, 17 O) by water distillation or nitric oxide distillation. However, conventional methods are costly and may have safety issues. In 2004, we developed the first unit of our novel oxygen isotope separation process by cryogenic oxygen distillation to overcome these issues. To meet the needs of the market, we built a second unit in 2013 and a third in 2016. We are now operating three commercially viable separation units with a total capacity of 600 kg of Water-18 O per year.

Ultra-compact, automated microdroplet radiosynthesizer.

Application of microfluidics offers numerous advantages in the field of radiochemistry and could enable dramatic reductions in the cost of producing radiotracers for positron emission tomography (PET). Droplet-based microfluidics, in particular, requires only microgram quantities of expensive precursors and reagents (compared to milligram used in conventional radiochemistry systems), and occupies a more compact footprint (potentially eliminating the need for specialized shielding facilities, i.e. hot cells). However, the reported platforms for droplet radiosynthesis have several drawbacks, including high cost/complexity of microfluidic reactors, requirement for manual intervention (e.g. for adding reagents), or difficulty in precise control of droplet processes. We describe here a platform based on a particularly simple chip, where reactions take place atop a hydrophobic substrate patterned with a circular hydrophilic liquid trap. The overall supporting hardware (heater, rotating carousel of reagent dispensers, etc.) is very simple and the whole system could be packaged into a very compact format (about the size of a coffee cup). We demonstrate the consistent synthesis of [18F]fallypride with high yield, and show that protocols optimized using a high-throughput optimization platform we have developed can be readily translated to this device with no changes or re-optimization. We are currently exploring the use of this platform for routine production of a variety of 18F-labeled tracers for preclinical imaging and for production of tracers in clinically-relevant amounts by integrating the system with an upstream radionuclide concentrator.

Investigation on the impact of three different quaternary methyl ammonium cartridges on the radiosynthetic yields of [18 F]fluoromethyl tosylate.

Our recent investigations for the radiosynthesis of [18 F]fluoromethyl tosylate have highlighted that choice of quaternary methyl ammonium (QMA) cartridge used during the radiosynthesis can significantly impact the radiochemical yields. Often the details of the QMA cartridge used in fluourine-18 syntheses are not fully described. However, our studies demonstrate that the type, the size, and nature (method by which it has been conditioned) of the QMA cartridge used during the radiosynthesis can make a significant impact in the labelling efficiency. This paper investigates the use of three QMA cartridges and demonstrates that radiochemical yield (decay corrected) of [18 F]fluoromethyl tosylate can increase from 46% to 60% by simply changing the QMA cartridge (and leaving all other reagents and labelling conditions exactly the same). These learnings may be applied to improve the radiochemical yields of a number of [18 F]-fluorinated tracers (and synthons), where the labelling step is base-sensitive to increase the radiochemical yield, thereby significantly benefiting the radiochemistry and nuclear medicine community. This paper also highlights the necessity of the radiochemistry community to ensure the details of QMA cartridges used in fluorine-18 chemistry are fully and accurately described, since this will improve the translation of radiochemical methods from one laboratory to another.

Ion-production efficiency of a singly charged ion source developed toward a 11C irradiation facility for cancer therapy.

The ion-production efficiency of a newly developed singly charged ion source (SCIS) has been investigated to discuss the possibility of it being used in an isotope separation on-line system that provides 11C ions for heavy-ion cancer therapy with simultaneous verification of the irradiation field using positron emission tomography. The SCIS uses a low-energy hollow electron beam to produce singly charged carbon ions efficiently. To deliver sufficient 11C ions to the treatment room from a limited amount of 11C molecules, which are produced from a boron compound target and proton-beam irradiation via the 11B(p,n)11C reaction, the SCIS must have high ion-production efficiency. To realize this high efficiency, the SCIS was designed using a three-dimensional particle-in-cell code in previous work. With the fabricated SCIS, we performed experiments to measure the efficiency of producing CO2 + ions from nonradioactive 12CO2 molecules and C+ ions from nonradioactive 12CH4 molecules. We found that the SCIS achieved efficiencies of εC+ =4×10-3 (0.4%) for C+ production and εCO2 + =0.107 (10.7%) for CO2 + production.

On-cartridge preparation and evaluation of 68Ga-, 89Zr- and 64Cu-precursors for cell radiolabelling.

INTRODUCTION: Indium-111 when formulated as indium-111 oxine remains the gold standard for long term cell tracking, whereas radiometals for improved PET applications still have to be established. We here describe the on-cartridge formation of gallium-68, zirconium-89 and copper-64 complexes in small volumes suitable for cell labelling, including labelling of red blood cells (RBC) and white blood cells (WBC) and their biological evaluation in vivo. METHODS: Small volumes (1-2 mL) of tracers (oxine, tropolone) were directly prepared on an anion exchange cartridge (Sep-Pak QMA). Cells were radiolabelled and the labelling efficiency and efflux were evaluated. The in vivo biodistribution of copper-64-labelled WBC using [64Cu][Cu(oxinate)2] and [64Cu][Cu(tropolonate)2] was monitored in an infection and inflammation animal model using BALB/c mice. RESULTS: On-cartridge concentration of gallium-68, zirconium-89 and copper-64 enabled formation of oxine and tropolone tracers in small volumes with good yields (≥50%) and quality (extraction ≥90%). Prepared tracers radiolabelled the RBC comparable to indium-111 tracers and in vivo biodistribution of copper-64 labelled WBC showed clear accumulation of cells at the site of infection and inflammation. CONCLUSIONS: This on-cartridge preparation method enables simple formation of various PET tracers for cell radiolabelling. Zirconium-89 and copper-64 tracers radiolabelled cells with sufficient stability. Due to their longer half-life this approach could be promising for routine applications where longer evaluation periods for cell tracking are needed. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: This novel approach for on-cartridge concentration and preparation of oxine and tropolone precursors with different positron emitters, in small volume and suitable pH, offers a versatile tool towards cell labelling for preclinical and clinical PET applications.

99 Mo recoil atoms yield in the 100 Mo(p,x) reaction on cyclotron irradiation of Mo nanofilms.

We study the possibility of increasing the specific activity of 99 Mo produced by irradiating molybdenum targets with the use of the Szilard-Chalmers effect. According to the Szilard-Chalmers effect, recoil atoms of the 99 Mo radionuclide can be produced in nuclear reactions and retained in surrounding buffer substance. The objective of our work is to measure the yield of recoil atoms in the buffer as a function of the molybdenum layer thickness. The yield of recoil 99 Mo atoms in the 100 Mo(p,x)99 Mo nuclear reaction as a function of metallic molybdenum nanolayer thickness has been measured. Measurements were carried out after irradiation of nanolayers in the U-150 cyclotron with 28-MeV protons. Nanolayers of molybdenum with thickness of 30 to 220 nm were produced by magnetron sputtering on sapphire plates. The yield of the mass of 99 Mo recoil atoms was found to be the highest with the molybdenum layer thickness of 80 ± 5 nm. The enrichment factor (EF) has been defined as a ratio of the 99 Mo collector specific activity (SA) to the entire target SA before separation as EF = 1200 ± 150. The specific activity of 99 Mo produced in the collector was estimated to be approximately equal to 25 Ci·g-1 .