A fully automated synthesis of [<sup>18</sup>F]‐FEAU and [<sup>18</sup>F]‐FMAU using a novel dual reactor radiosynthesis module

Paolillo, Vincenzo; Riese, Stefan; Gelovani, Juri G.; Alauddin, Mian M.

doi:10.1002/jlcr.1674

Cited by 23 publications

(9 citation statements)

References 53 publications

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“…Further, the fluorine exchange from TMSOTf or one of the byproducts may result in lower specific activity. Our [ 18 F]-FMAU and [ 18 F]-FEAU (Table 4) synthesis afforded 2–3 fold lower specific activities than the highest specific activity reported in the literature (Table 4) [15, 18, 33, 36]. We obtained the highest specific activity with this method for [ 18 F]-FIAU.…”

Section: Resultsmentioning

confidence: 67%

An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nucleosides

Zhang¹,

Cantorias²,

Pillarsetty³

et al. 2012

Nuclear Medicine and Biology

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The expression of the herpes simplex virus type-1 thymidine kinase (HSV1-tk) gene can be imaged efficaciously using a variety of 2′-[18F]fluoro-2′-deoxy-1-b-D-arabinofuranosyl-uracil derivatives [[18F]-FXAU, X= I(iodo), E(ethyl), and M(methyl)]. However, the application of these derivatives in clinical and translational studies has been impeded by their complicated and long syntheses (3–5 h). To remedy these issues, in the study at hand we have investigated whether microwave or combined catalysts could facilitate the coupling reaction between sugar and nucleobase and, further, have probed the feasibility of establishing a novel approach for [18F]-FXAU synthesis. We have demonstrated that the rate of the trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed coupling reaction between the 2-deoxy-sugar and uracil derivatives at 90°C can be significantly accelerated by microwave-driven heating or by the addition of Lewis acid catalyst (SnCl4). Further, we have observed that the stability of the α- and β-anomers of [18F]-FXAU derivatives differs during the hydrolysis step. Using the microwave-driven heating approach, overall decay-corrected radiochemical yields of 19–27% were achieved for [18F]-FXAU in 120 min at a specific activity of >22 MBq/nmol (595 Ci/mmol). Ultimately, we believe that these high yielding syntheses of [18F]-FIAU, [18F]-FMAU and [18F]-FEAU will facilitate routine production for clinical applications.

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Section: Resultsmentioning

confidence: 67%

An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nucleosides

Zhang¹,

Cantorias²,

Pillarsetty³

et al. 2012

Nuclear Medicine and Biology

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“…[ 18 F]FMAU synthesis requires four steps; therefore, it is difficult to adapt for automated production. A dual‐reactor module from GE Healthcare has been tested and reported for the automated synthesis of [ 18 F]FMAU and [ 18 F]FEAU . Although this direct fluorination method produced low yields, it has a high potential for routine production of [ 18 F]FMAU via automation.…”

Section: Discussionmentioning

confidence: 99%

“…The synthesis time was 3.5 h. This methodology was extended for syntheses of other [ 18 F]‐labeled 2′‐arabino‐pyrimidine nucleoside analogs . Recently, a prototype dual‐reactor module was used for the automated synthesis of [ 18 F]FMAU and 2′‐[ 18 F]fluoro‐5‐ethyl‐1‐ β ‐ d ‐arabinofuranosyluracil ([ 18 F]FEAU) using this method . The method has been modified using Friedel–Crafts catalyst trimethylsilyltrifluoromethanelsulfonate and applied to automated synthesis using a one‐pot reactor that is compatible with commercial modules .…”

Section: Biochemical Substrates Specific For Thymidine Kinase Type 1 mentioning

confidence: 99%

Nucleoside‐based probes for imaging tumor proliferation using positron emission tomography

Alauddin

2013

Labelled Comp Radiopharmac

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Cancer is one of the leading causes of human death, and early detection can be beneficial for its timely therapy and management. For the early detection of cancer, positron emission tomography (PET) is more accurate and sensitive than other imaging modalities, such as computed tomography and magnetic resonance imaging. [(18) F]-Labeled fluorodeoxyglucose is the most useful PET probe in early detection of cancer; however, its nonspecific accumulation and consequent false-positive findings warrant the identification of other PET probes. Thymidine (TdR) and its analogs have been radiolabeled for PET imaging of cellular proliferation and DNA synthesis. Because of its in vivo instability, radiolabeled TdR has not been successful in PET imaging. However, some of its radiolabeled analogs have been developed for PET imaging of cellular proliferation and DNA synthesis. In this review, the radiochemistry and production of (11) C-TdR and (11) C/(18) F-labeled TdR analogs published to date are presented.

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“…For many years, the maximum pressure rating of these valves was in the ~30-50 psi range, but some modern valves can reach ~70-100 psi operating limit. In addition to the lower operating pressure, systems with tubing and valves connected to the reaction vessel during heating could also suffer from a redistribution of solvent from the vessel into the tubing (Amarasekera et al, 2013;Paolillo et al, 2009).…”

Section: Seal Integrity Testingmentioning

confidence: 99%

Understanding temperatures and pressures during short radiochemical reactions

Lazari¹,

Irribarren²,

Zhang³

et al. 2016

Applied Radiation and Isotopes

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Automated radiosynthesizers are critical for the reliable, routine production of PET tracers. To perform reactions in these systems, the temperature of the reactor heater is controlled, and the liquid temperature within the reaction vessel is presumed to closely follow. In reality, the liquid temperature can lag by several minutes and generally does not reach the heater temperature. Furthermore, because different synthesizers have different heating mechanisms and geometries, discrepancies are certain to exist between the actual temperatures experienced by the reaction mixture on different synthesizers. For dissimilar reactors, this can necessitate re-optimization of conditions when adapting a synthesis from one system to another, especially for the short-duration reactions common in radiochemistry. Herein, we study the relationship between the temperatures of the reactor heater and reaction liquid for various solvents using the ELIXYS radiosynthesizer as a representative example of a vial-based system. Our aims are to quantitatively illustrate this discrepancy to the community and provide data necessary to enable efficient translation of protocols between other radiosynthesizers and the ELIXYS.

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A fully automated synthesis of [¹⁸F]‐FEAU and [¹⁸F]‐FMAU using a novel dual reactor radiosynthesis module

Cited by 23 publications

References 53 publications

An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nucleosides

An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nucleosides

Nucleoside‐based probes for imaging tumor proliferation using positron emission tomography

Understanding temperatures and pressures during short radiochemical reactions

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A fully automated synthesis of [18F]‐FEAU and [18F]‐FMAU using a novel dual reactor radiosynthesis module

Cited by 23 publications

References 53 publications

An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nucleosides

An improved strategy for the synthesis of [18F]-labeled arabinofuranosyl nucleosides

Nucleoside‐based probes for imaging tumor proliferation using positron emission tomography

Understanding temperatures and pressures during short radiochemical reactions

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A fully automated synthesis of [¹⁸F]‐FEAU and [¹⁸F]‐FMAU using a novel dual reactor radiosynthesis module