Preparation of 177Lu-PSMA-617 in Hospital Radiopharmacy: Convenient Formulation of a Clinical Dose Using a Single-Vial Freeze-Dried PSMA-617 Kit Developed In-House.

OBJECTIVE: In the recent time, endoradionuclide therapy for metastatic castration-resistant prostate carcinoma employing 177Lu-PSMA-617 has yielded encouraging results and several clinical trials with the agent are currently ongoing. Routine preparation of 177Lu-PSMA-617 patient doses can be made simpler and convenient, if the ingredients essential for radiolabeling are made available in a ready-to-use lyophilized form. METHODS: PSMA-617 freeze-dried kit was formulated and used for the preparation of 177Lu-PSMA-617 clinical dose with high radiochemical purity using low/medium specific activity 177Lu. Detailed radiochemical studies were performed to determine the maximum activity and volume of 177LuCl3, which can be added in the kit for the formulation of 177Lu-PSMA-617. Studies were also performed to determine the shelf life of the kit to ensure its long-term usage. Studies were performed in buffer as well as human serum medium to determine the stability of the 177Lu-PSMA-617 complex after storing in respective media up to 7 days postpreparation. About ten patient doses of 177Lu-PSMA-617 were administered, and posttherapy scans were acquired. RESULTS: The formulated freeze-dried kit of PSMA-617 could be radiolabeled with an average percentage radiochemical purity > 98.53 ± 0.38. The freeze-dried kit was found suitable for tolerating up to 0.5 mL of 177LuCl3 (in 0.01 N HCl) and specific activity of 555 MBq/µg (15 mCi/µg) for the preparation of the patient dose of 177Lu-PSMA-617. The 177Lu-PSMA-617 complex prepared using the freeze-dried kit of PSMA-617 was observed to maintain % radiochemical purity (RCP) of 96.74 ± 0.87 and 94.81 ± 2.66, respectively, even after storing up to 7 days in buffer and human serum, respectively. 177Lu-PSMA-617 prepared using the in-house formulated freeze-dried kit of PSMA-617 exhibited accumulation in metastatic lesions picked up in a pretherapy PET scan. Reduction in number as well as size of lesions was observed in posttherapy scans acquired after two months of administering the first therapeutic dose of 177Lu-PSMA-617. CONCLUSIONS: The freeze-dried kit of PSMA-617 could be used for the preparation of 177Lu-PSMA-617 with high radiochemical purity (>98%) in a reproducible manner. 177Lu-PSMA-617 prepared using the developed kit was successfully evaluated in patients suffering from metastatic prostate cancer.

Improved small scale production of iodine-124 for radiolabeling and clinical applications.

AIM: This work describes a small-scale production of iodine-124 using a 16.5 MeV cyclotron, and a subsequent validation of the formulated sodium [124I]iodide solution for routinely clinical applications. METHODS: Iodine-124 (124I) was produced via the 124Te(p, n)124I reaction using a 16.5 MeV GE PETtrace® cyclotron. Irradiation was performed with a pre-prepared solid target consisting of [124Te]TeO2 (99.93%) and Al2O3. Different layer thicknesses, irradiation and extraction parameters were tested. After irradiation at the cyclotron, the shuttle with irradiated material was transferred fully automatically via a tube system to the Comecer ALCEO® Halogen 2.0 extraction unit. Iodine-124 was subsequently extracted in form of sodium [124I]iodide ([124I]NaI) in 0.05 N aqueous NaOH solution, followed by reconstitution and validation for preclinical and clinical uses. RESULTS: Good result was achieved using a beam degradation foil of 500 µm thickness in combination with beam currents between 10 and 15 µA. Under these conditions, up to 150 MBq no-carrier-added [124I]NaI was obtained after a 2 h irradiation time in less than 500 µl 0.05 N NaOH. Isolation of [124I]NaI, including evaporation and extraction at the ALCEO® Halogen EVP unit was accomplished in 90 min 24 h after production (irradiation), the amount of iodine-123 as assessed by gamma-ray spectroscopy was less than 1.5%. The undesirable iodine-125 was not detectable by gamma spectroscopy. The extracted [124I]NaI could be used directly for radiolabeling purposes, and after buffering with phosphate buffered saline (PBS) and sterile filtration for clinical applications. CONCLUSIONS: Through the optimized conditions for irradiation and extraction, iodine-124 was produced in good radiochemical yields and high radionuclide purity. The generated injectable [124I]NaI solution was sterile, non-pyrogenic and ready for preclinical and clinical applications after a sterile filtration through a 0.22 µm membrane filter.

Study of the peak splitting in an alternative method for the radiochemical purity measurement of 99mTechnetium-sestamibi.

One of the alternative methods for the measurement of radiochemical purity (RCP) of Technetium-sestamibi uses Whatman 3MM paper as the stationary phase and ethyl acetate as the mobile phase. However, alternative method shows peak splitting and shouldering of the radiopharmaceutical. This could be because of higher levels of analyte. We aimed to assess the effect of sample dilution (1 : 1) on this method and to compare these RCP values with the reference method. The diluted samples showed a unique peak in the radiopharmaceutical zone, but the RCP values were significantly different (P<0.05) and correlated poorly with the reference method.

Continuation of comprehensive quality control of the itG 68Ge/68Ga generator and production of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC for clinical research studies.

Performance of a second itG 68Ge/68Ga generator system and production of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC were tested over one year as an accompaniment to a previously published study (J Nucl Med. 2016;57:1402-1405). METHODS: Performance of a 1951MBq 68Ge/68Ga generator was characterized and the eluate used for preparation of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC. Weekly elution profiles of 68Ga elution yield and 68Ge breakthrough were determined. RESULTS: 68Ga elution yields averaged 82% (61.8-98.4%) and 68Ge breakthrough averaged 0.002% (0.0007% to 0.004%). The radiochemical purities of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC were determined by HPLC analysis to be >98% and specific activity was 12.6 and 42GBq/µmol, respectively. 68Ge contamination in the product was under the detection limit (0.00001%). Final sterile, pyrogen-free formulation of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC in physiologic saline with 5%-7% ethanol was achieved. CONCLUSION: Performance of a 68Ge/68Ga generator was studied over one year with satisfactory results. The generator eluate was used to synthesize 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC on a routine basis in high purity.

Efficient preparation of high-quality 64Cu for routine use.

INTRODUCTION: Copper-64 is an attractive radionuclide for positron emission tomography and is emerging as a radiotherapeutic agent. The demand of 64Cu with low metallic impurities has increased because of its wide applications when incorporated with antibodies, peptides, and proteins. In this study, we propose a new separation method to produce high-quality 64Cu using a cation exchange column, as well as an automated separation system suitable for large-scale production. METHODS: 64Cu was produced from an electrodeposited 64Ni target via the 64Ni(p,n)-reaction with a 24MeV HH+ beam at 10eµA (electrical microampere) conducted for 1-3h. The irradiated target was transported to a hot cell and disassembled remotely. 64Cu was separated by a solvent mixture of HCl and acetone on a cation-exchange resin, AG50W-X8. The chemical purity of 64Cu final product was evaluated using ion-chromatography coupled with a UV detector and inductively coupled plasma mass spectroscopy for quality as well as metallic impurities. RESULTS: We obtained 64Cu in dried form at a yield of 5.2-13GBq at the end of separation, or 521±12MBq/eµAh as the final product within 2.5h of processing time. The metallic impurities were a satisfactory low level in the order of ppb. Major contaminants of Co and Ni were lower than those samples obtained by a widely accepted separation using an anion-exchange resin. CONCLUSION: Using a cation-exchange resin and a systematic operation, we successfully reduced the contamination level of the 64Cu product. As a straightforward separation method, which shortened the entire processing time, we obtained a satisfactory amount of high-quality 64Cu available for routine use.

Radiosynthesis and quality control of [11C]TASP457 as a clinically useful PET ligand for imaging of histamine H3 receptors in human brain.

INTRODUCTION: Recently, 6-[(1-cyclobutylpiperidin-4-yl)oxy]-1-(6-[11C]methoxypyridin-3-yl)-3,4-dihydroquinolin-2(1H)-one ([11C]TASP457, [11C]2) has been developed as a novel PET ligand for histamine H3 receptors in brain. [11C]2 is potentially suitable for imaging H3 receptors in rat and monkey brains, which has motivated us to perform first-in-human study of [11C]2 for qualifying H3 receptors in human brain. In this paper, we report an efficient radiosynthesis of [11C]2 to obtain sufficient radioactivity and high quality for clinical application. METHODS: In manual synthesis, we optimized the reaction conditions of desmethyl precursor 1, which contains a 2-hydroxypyridine moiety, with [11C]MeI or [11C]MeOTf. After optimization, we performed automated synthesis and quality control of [11C]2. RESULTS: Bubbling [11C]MeOTf into a heated mixture of precursor 1 and cesium carbonate in DMF at 100°C for 90s produced [11C]2 with decay-corrected radiochemical yields of (based on [11C]CO2) 7.9±1.8% (n=78). The specific activity of [11C]2 was 156±52GBq/µmol (n=78) at the end of synthesis. The total synthesis time was approximately 35min from the end of bombardment. All the quality control results of [11C]2 were in compliance with our in-house quality control/assurance specifications. CONCLUSION: We radiosynthesized [11C]TASP457 ([11C]2) with sufficient amounts of radioactivity and high quality for clinical usefulness. This radioligand is being used for PET assessment of H3 receptors in human brain in our facility.

A two-center study for the quality control of [(18)F]FDG using FASTlab phosphate cassettes.

OBJECTIVE: The GE FASTlab radiosynthesis module is routinely used for the production of [(18)F]FDG, utilizing the commercially available phosphate cassettes. Because of the observation of a white precipitate in the product vial before the product expiry time, we re-examined the quality of the produced [(18)F]FDG solution. METHODS: Phosphate buffered [(18)F]FDG solution was synthesized on the FASTlab and analyzed at both National Taiwan University Hospital (NTUH) of Taiwan and Royal Brisbane and Women's Hospital (RBWH) of Australia. In addition to the standard product quality control (QC), the concentration of aluminum (Al(3+)) as probable cause of the precipitations in the [(18)F]FDG solution was analyzed by inductively coupled plasma mass spectrometry (ICP-MS at RBWH) and inductively coupled plasma optical emission spectrometry (ICP-OES at NTUH), and using three semi-quantitative methods at NTUH, Advantec(®) Alumi Check Test Strip, Quantofix(®) Aluminum Test Strip and MColortest™ Aluminum Test kit. RESULTS: The precipitates were observed in the [(18)F]FDG solution within 24 (NTUH) and 6 (RBWH) hours after the end of synthesis in 38-100 % of the batches, dependent on the batch of the FASTlab cassettes. Addition of metal-free HCl(aq) to aliquots of [(18)F]FDG containing precipitate, followed by ICP-MS analysis revealed Al(3+) concentrations of 70-80 ppm. Al(3+) concentrations of 10-12 ppm were detected in [(18)F]FDG batches that did not show any precipitation. In contrast, less than 5 ppm of the residual Al(3+) was detected by semi-quantitative methods in all batches. CONCLUSION: The US (USP), British (BP), European (EP) and Japanese (JP) pharmacopeias demand that [(18)F]FDG for injection should be clear and particulate free within the given shelf-life/expiration time. To avoid Al-phosphate precipitation within the product expiry time, FASTlab citrate cassettes, rather than phosphate cassettes, should be used for [(18)F]FDG production. Although testing for Al(3+) is not listed in the [(18)F]FDG monographs of the USP, BP and EP, residual Al(3+) levels should be considered in the interests of patient safety.

Synthesis of a doxycycline-[(13) CD3 ] standard.

A stable isotope labelled mass spectrometry internal standard of the antibiotic doxycycline was prepared to assist in pharmacokinetic analyses. Our approach was to first N-demethylate doxycycline using a non-classical Polonovski reaction and then re-methylate using methyl-[(13) CD3 ] iodide, which gave doxycycline-[(13) CD3 ] with an isotopic purity of 99%.

Uso de radiofármacos metales en PET. La nueva realidad / The use of metal radiotracers in PET: the new reality

No disponible

Relación entre la pureza radioquímica del 123i-ioflupano y la captación extracraneal (tiroidea y parotídea) / Relationship between radiochemical purity of 123i-ioflupane and extracranial image captation (parotid and thyroid

Objetivo. Estudiar el efecto de la pureza radioquímica (PR) del 123I-Ioflupano, utilizado para realizar SPECT cerebral de transportadores de dopamina, sobre las imágenes obtenidas y evaluar la posible influencia de la extravasación durante su administración y del grado de afectación del paciente por el síndrome parkinsoniano sobre los resultados. Material y métodos. Se realizó un estudio prospectivo en 39 pacientes. La PR del 123I-Ioflupano se determinó mediante cromatografía en capa fina. Se delimitaron las regiones de interés (ROI) en zona aproximada de cerebro, parótidas y región cervical, obteniéndose la media de cuentas en cada región y las ratios de actividad tiroides/cerebro (RTC) y parótidas/cerebro (RPC). Se propuso un modelo de regresión lineal múltiple con predictores cuantitativos y categóricos. Resultados. El modelo mostró correlación entre la PR y la RTC modificada por la presencia de extravasación, fue estadísticamente significativo (p<0,001 y predijo el 42,31% de la variabilidad de la RTC. La correlación entre PR y RPC no se modificó por ninguna de las variables propuestas. El modelo fue estadísticamente significativo (p<0,0176) y predijo el 12,3% de la variabilidad del RPC. Conclusiones. La capacidad predictiva del modelo para explicar la variabilidad de la RTC es aceptable y explica la repercusión negativa de la extravasación. Sin embargo, la capacidad para explicar la variabilidad de la RPC es baja y debe ser atribuida a variables no estudiadas. Una PR baja y la extravasación durante la administración del radiofármaco se traduce en mayor actividad extracraneal e implica peor calidad de imagen y mayor irradiación tiroidea

Aim. The aim of this study is to see the effect of radiochemical purity (PR) of 123I- Ioflupane used for cerebral dopamine transporter SPECT (Single Photon Emission Computed Tomography) on the images and evaluate the possible influence of extravasation during the administration in patient with Parkinson syndrome. Material and methods. A Prospective study was performed in 39 patients. The PR of 123I-Ioflupane was determined by radiochromatography. The regions of interest (ROI) were defined in general area of the brain, parotid and cervical region, obtaining the average counts in each region and activity ratios thyroid / brain (RTC) and parotid / brain (RPC). It was proposed a model of multiple linear regression with quantitative and categorical predictors Results. The model showed that correlation between the PR and the RTC was modified by the presence of extravasation, it was statistically significant (p < 0.001) and predicted the 42.31 % of the variability of the RTC. The correlation between PR and PRC was not modified by any of the variables proposed. The model was statistically significant (p < 0.0176) and 12.3% predicted variability RPC Conclusions. The predictive variability of the model of RTC is acceptable and explains the negative impact of extravasation. However, the ability to explain the variability of the PRC is low and should not be attributed to variables studied. A low PR and extravasation during the administration of the radiopharmaceutical involves worse quality of image and increased thyroid irradiation

The development of an automated and GMP compliant FASTlab™ Synthesis of [(18) F]GE-180; a radiotracer for imaging translocator protein (TSPO).

The level of the translocator protein (TSPO) increases dramatically in microglial cells when the cells are activated in response to neuronal injury and insult. The radiotracer [(18) F]GE-180 binds selectively and with high affinity to TSPO and can therefore be used to measure neuroinflammation in a variety of disease states. An optimized, automated synthesis of [(18) F]GE-180 has been developed for the GE FASTlab™ synthesizer. The entire process takes place on the single-use cassette. The radiolabelling is performed by nucleophilic fluorination of the S- enantiomer mesylate precursor. The crude product is purified post-radiolabelling using two solid-phase extraction cartridges integrated on the cassette. Experimental design and multivariate data analysis were used to assess the robustness, and critical steps were optimized with respect to efficacy and quality. The average radiochemical yield is 48% (RSD 6%, non-decay corrected), and the synthesis time including purification is approximately 43 min. The radiochemical purity is ≥95% for radioactive concentration ≤1100 MBq/mL. The total amount of precursor-related chemical impurities is 1-2 µg/mL. The use of solid-phase extraction purification results in a robust GMP compliant process with a product of high chemical and radiochemical purity and consistent performance across positron emission tomography (PET) centers.

Validación de fases estacionarias en la cromatografía planar de 111In-pentetreótida / Validation of stationary phases in 111In-pentetreotide planar chromatography

Introducción: Tras el cese en la fabricación de ITLC-SG por Pall-Gelman, es necesaria la validación de fases estacionarias alternativas. Objetivo: Validar diferentes fases estacionarias frente a ITLC-SG de Pall-Gelman en la determinación de la pureza radioquímica (PRQ) de 111In-pentetreótida (111In-Octreoscan) por cromatografía planar. Material y métodos: Realizamos un estudio caso-control en el que incluimos 66 preparaciones de 111In-pentetreótida. Determinamos la PRQ mediante cromatografía plana, empleando una solución recién preparada de citrato de sodio de 0,1 M (pH 5) y las siguientes fases estacionarias: ITLC-SG (Pall-Gelman) (método de referencia), iTLC-SG (Varian), Silicagel 60 HPTLC (Merck), Whatman 1, Whatman 3 MM y Whatman 17. Para cada uno de los métodos calculamos: PRQ, factores de retención (RF) del radiofármaco e 111In libre, tiempo de desarrollo cromatográfico y resolución entre picos. Comparamos los resultados obtenidos con los del método de referencia. Para el análisis estadístico de datos utilizamos el programa SPSS. Para el estudio de significación estadística calculamos el valor de p. Resultados: Con Silicagel 60 HPTLC (Merck) se obtiene la mayor resolución, aunque el tiempo de desarrollo cromatográfico es prolongado (media = 33,62 min). Con iTLC-SG (Varian) se obtiene una resolución mayor que con el método de referencia, siendo menor el tiempo de desarrollo cromatográfico (media = 3,61 min). Con papel Whatman se obtienen resoluciones muy bajas, fundamentalmente con Whatman 1 y 3 MM, por lo que no recomendamos su utilización. Conclusiones. Aunque iTLC-SG (Varian) y Silicagel 60 HPTLC (Merck) son alternativas adecuadas a ITLC-SG (Pall-Gelman) en la determinación de la PRQ de 111In-pentetreótida, iTLC-SG (Varian) es el método de elección por su menor tiempo de desarrollo cromatográfico(AU)

Introduction: Since Pall-German stopped manufacturing ITLC-SG, it has become necessary to validate alternative stationary phases. Objective: To validate different stationary phases versus ITLC-SG Pall-Gelman in the determination of the radiochemical purity (RCP) of 111In-pentetreotide (111In-Octreoscan) by planar chromatography. Material and methods: We conducted a case-control study, which included 66 111In-pentetreotide preparations. We determined the RCP by planar chromatography, using a freshly prepared solution of 0,1 M sodium citrate (pH 5) and the following stationary phases: ITLC-SG (Pall-Gelman) (reference method), iTLC-SG (Varian), HPTLC silica gel 60 (Merck), Whatman 1, Whatman 3 MM and Whatman 17. For each of the methods, we calculated: PRQ, relative front values (RF) of the radiopharmaceutical and free 111In, chromatographic development time, resolution between peaks. We compared the results obtained with the reference method. The statistical analysis was performed using the SPSS program. The p value was calculated for the study of statistical significance. Results: The highest resolution is obtained with HPTLC silica gel 60 (Merck). However, the chromatographic development time is too long (mean = 33.62 minutes). Greater resolution is obtained with iTLC-SG (Varian) than with the reference method, with lower chromatographic development time (mean = 3.61 minutes). Very low resolutions are obtained with Whatman paper, essentially with Whatman 1 and 3 MM. Therefore, we do not recommend their use. Conclusions: Although iTLC-SG (Varian) and HPTLC silica gel 60 (Merck) are suitable alternatives to ITLC-SG (Pall-Gelman) in determining the RCP of 111In-pentetreotide, iTLC-SG (Varian) is the method of choice due to its lower chromatographic development time(AU)

Description of high purity and high specific activity of [11C]Choline synthesis using TRACERlab FXc module, and detailed report of quality controls.

We proposed a method of synthesis to produce [11C]Choline using TRACERlab FXc module that utilized gas phase iodination. The product had radiochemical purity of 99.79 ± 0.14 % and specific activity of 45.7 ± 7.59 GBq/µmol. [11C]Choline did not have at the moment a specific monograph in European Pharmacopeia therefore we used, when possible, as quality controls reference the monograph of [18F]FDG and we proposed suitable methods to verify radiochemical purity and to quantify residual DMAE and choline amounts.

Preparation of proton rich radionuclides in support of radiochemical analysis.

The production of proton rich radionuclides supports a wide range of radiochemical analyses via radioactive yield tracers ((95m)Tc and (236)Pu). In recent years, NPL and the University of Birmingham cyclotron have collaborated to produce these, and other, radionuclides.

Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions.

The DOTA macrocyclic ligand can form stable complexes with many cations besides yttrium and lutetium. For this reason, the presence of competing cationic metals in yttrium-90 and lutetium-177 chloride solutions can dramatically influence the radiolabeling yield. The aim of this study was to evaluate the coordination yield of yttrium- and lutetium-DOTATATE complexes when the reaction is performed in the presence of varying amounts of competing cationic impurities. In the first set of experiments, the preparation of the samples was performed by using natural yttrium and lutetium (20.4 nmol). The molar ratio between DOTATATE and these metals was 1 to 1. Metal competitors (Pb(2+), Zn(2+), Cu(2+), Fe(3+), Al(3+), Ni(2+), Co(2+), Cr(3+)) were added separately to obtain samples with varying molar ratio with respect to yttrium or lutetium (0.1, 0.5, 1, 2 and 10). The final solutions were analyzed through ultra high-performance liquid chromatography with an UV detector. In the second set of experiments, an amount of (90)Y or (177)Lu chloride (6 MBq corresponding to 3.3 and 45 pmol, respectively) was added to the samples, and a radio-thin layer chromatography analysis was carried out. The coordination of Y(3+) and Lu(3+) was dramatically influenced by low levels of Zn(2+), Cu(2+) and Co(2+). Pb(2+) and Ni(2+) were also shown to be strong competitors at higher concentrations. Fe(3+) was expected to be a strong competitor, but the effect on the incorporation was only partly dependent on its concentration. Al(3+) and Cr(3+) did not compete with Y(3+) and Lu(3+) in the formation of DOTATATE complexes.

Fully automated one-pot radiosynthesis of O-(2-[18F]fluoroethyl)-L-tyrosine on the TracerLab FX(FN) module.

INTRODUCTION: An efficient fully automated method for the radiosynthesis of enantiomerically pure O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) using the GE TracerLab FX(FN) synthesis module via the O-(2-tosyloxyethyl)-N-trityl-L-tyrosine tert-butylester precursor has been developed. METHODS: The radiolabelling of [(18)F]FET involved a classical [(18)F]fluoride nucleophilic substitution performed in acetonitrile using potassium carbonate and Kryptofix 222, followed by acid hydrolysis using 2N hydrochloric acid. RESULTS: [(18)F]FET was produced in 35±5% (n=22) yield non-decay-corrected (55±5% decay-corrected) and with radiochemical and enantiomeric purity of >99% with a specific activity of >90 GBq/µmol after 63 min of radiosynthesis including HPLC purification and formulation. CONCLUSION: The automated radiosynthesis provides high and reproducible yields suitable for routine clinical use.

The improved syntheses of 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) using a multistep one-pot strategy.

INTRODUCTION: We and others have previously reported a four-step radiosynthesis of a series of 2'-deoxy-2'-[(18)F]fluoro-5-substituted-1-ß-D-arabinofuranosyluracil derivatives including [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU as thymidine derivatives for tumor proliferation and/or reporter gene expression imaging with positron emission tomography (PET). Although the radiosynthesis has been proven to be reproducible and efficient, this complicated multistep reaction is difficult to incorporate into an automated cGMP-compliant radiosynthesis module for routine production. Recently, we have developed a simple and efficient one-pot method for routine production of [(18)F]FMAU. In this study, we studied the feasibility of radiosynthesizing [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU using this newly developed method. METHODS: Similar to the radiosynthesis of [(18)F]FMAU, 5-substituted 2'-[(18)F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU) were synthesized in one-pot radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS. RESULTS: This one-pot radiosynthesis method could be used to produce [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU. The overall radiochemical yields of these tracers varied from 4.1%±0.8% to 10.1%±1.9% (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150 min from the end of bombardment, and the radiochemical purity was >99%. CONCLUSIONS: The improved radiosyntheses of [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU have been achieved with reasonable yields and high purity using a multistep one-pot method. The synthetic time has been reduced, and the reaction procedures have been significantly simplified. The success of this approach may make PET tracers [(18)F]FAU, [(18)F]FEAU, [(18)F]FFAU, [(18)F]FCAU, [(18)F]FBAU and [(18)F]FIAU more accessible for preclinical and clinical research.